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  • 1
    In: British Journal of Cancer, Springer Science and Business Media LLC, Vol. 83, No. 11 ( 2000-12), p. 1454-1461
    Type of Medium: Online Resource
    ISSN: 0007-0920 , 1532-1827
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    Language: Unknown
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2000
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  • 2
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 69, No. 24_Supplement ( 2009-12-15), p. 6087-6087
    Abstract: Background: Detection of circulating tumor cells (CTC) is an independent prognostic factor in MBC. A decrease of CTC during treatment is associated with a better outcome (Cristofanilli, NEJM 2004). The antiangiogenic agent Bv, in combination with CT, (i) improves progression free survival (PFS) of first line treatments, (ii) may modify tumor cell intravasation and CTC count, and (iii) may change CEC levels. We therefore investigated whether CTC and CEC counts could be early surrogate markers of time to progression (TTP) in MBC patients receiving a highly active anti-tumor treatment (HAATT) comprising taxanes combined with Bv.Methods: Eligible patients received Bv (10mg/kg q2w or 15mg/kg q3w) combined with a taxane–based CT or non-anthracycline CT, until disease progression, unacceptable toxicity or withdrawal. For patients participating in the sub-study, CTC and CEC were measured in 7.5ml of blood at baseline and after cycle 2 or 3 of treatment. Analysis was performed using the CellSearch™ System, combining EpCAM immunomagnetic selection (IMS) followed by anti-cytokeratin (A45B/B3) staining for CTC and CD146 IMS and CD105 staining for CEC. VEGF-A constitutional polymorphisms from blood (2578C & gt;A, -1498T & gt;C, -634G & gt;C, 936C & gt;T) were also analyzed in the same patients. CTC and CEC counts at baseline and changes during treatment were correlated with TTP.Results: Sixty-seven patients were included. There was no correlation between CTC, CEC levels and VEGF-A polymorphisms. At baseline, using the threshold of 5 CTC/7.5 ml which was previously defined with standard CT: (i) CTC positivity (54% of patients) was associated with elevated LDH (p=0.04), elevated CA15.3 (p & lt;0.001) and high tumor burden ( & gt;3 metastatic sites) (p=0.03); (ii) CTC was a significant prognostic marker for TTP at a threshold of 3 CTC/7.5 ml (p & lt;0.05) and not at 5 CTC/7.5 ml (p=0.09). Baseline CEC levels (median:17, range [1-769]) were associated with age ≥45y (p=0.01), with elevated LDH (p & lt;0.01) and not with TTP at any threshold. In our series, changes of CTC count during treatment was not a surrogate for TTP, with any of the model tested (threshold-based or relative decrease in %). However, changes of CEC count during treatment was significantly associated with TTP, at the threshold of 20 (p & lt;0.001).Conclusion: Our study is the first to monitor both CTC and CEC levels in the era of HAATT comprising an antiangiogenic agent combined with standard CT. We observed that previously reported CTC thresholds may be modified by antiangiogenic therapy, whereas changes in CEC levels are a promising early surrogate marker for TTP under HAATT. Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 6087.
    Type of Medium: Online Resource
    ISSN: 0008-5472 , 1538-7445
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    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2009
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    detail.hit.zdb_id: 410466-3
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  • 3
    Online Resource
    Online Resource
    American Association for Cancer Research (AACR) ; 2011
    In:  Cancer Research Vol. 71, No. 24_Supplement ( 2011-12-15), p. P4-07-18-P4-07-18
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 71, No. 24_Supplement ( 2011-12-15), p. P4-07-18-P4-07-18
    Abstract: Purpose: Circulating tumors cells (CTC) have been recently proposed as a new dynamic blood marker whose positivity at baseline is a prognostic factor and whose changes under treatment are correlated with progression-free survival (PFS) in metastatic breast cancer patients. However, serum markers levels are also used for the same purpose, and no clear comparison as been reported to date. Patients and methods: The IC 2006–04 enrolled prospectively 267 metastatic breast cancer patients treated by first line chemotherapy and confirmed that CTC levels are an independent prognostic factor for PFS and Overall survival (OS). A pre-planned endpoint was to compare prospectively the positivity rates and the value of CTC (CellSearch®), of serum tumor markers (CEA, CA 15–3, CYFRA 21.1), and of serum non-tumor markers (LDH, ALP) at baseline and under treatment for PFS prediction, independently from the other known prognostic factors, using univariate analyses and concordance indexes. Results: Table 1 shows the incidence of each of the 6 blood markers. Assessing all the 6 markers retrieved 90% of patients with at least one elevated marker at baseline. Interestingly, a combination of two markers (CA 15–3 and CYFRA 21.1, often used in lung cancer) retrieved 86% of patients with at least one marker elevated at baseline. All 6 markers were correlated with poor performance status, high number of metastatic sites and with each other. Each marker was associated, when elevated at baseline, with a significantly shorter PFS in univariate anlaysis. Serum marker changes during treatment, assessed either between baseline and week 3 or between baseline and week 6–9, were significantly associated with PFS, as reported for CTC. Concordance indexes comparison showed no clear superiority of any of the serum marker or CTC for PFS prediction. Conclusion: In the largest prospective CTC study in metastatic breast breast cancer, we previously reported that CTC count, but not serum markers, is an independent prognostic factor for PFS and overall survival. However, for the purpose of PFS prediction by measuring blood marker changes during treatment, currently available blood-derived markers (CTC and serum markers) had globally similar performances. Besides CEA and CA 15–3, CYFRA 21.1 is commonly elevated in metastatic breast cancer and has a strong prognostic value. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P4-07-18.
    Type of Medium: Online Resource
    ISSN: 0008-5472 , 1538-7445
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    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2011
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  • 4
    In: British Journal of Ophthalmology, BMJ, Vol. 92, No. 4 ( 2008-04-01), p. 579-580
    Type of Medium: Online Resource
    ISSN: 0007-1161
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    Language: English
    Publisher: BMJ
    Publication Date: 2008
    detail.hit.zdb_id: 1482974-5
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  • 5
    Online Resource
    Online Resource
    American Society of Clinical Oncology (ASCO) ; 2010
    In:  Journal of Clinical Oncology Vol. 28, No. 15_suppl ( 2010-05-20), p. 8018-8018
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 28, No. 15_suppl ( 2010-05-20), p. 8018-8018
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
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    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2010
    detail.hit.zdb_id: 2005181-5
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  • 6
    Online Resource
    Online Resource
    American Society for Microbiology ; 1989
    In:  Infection and Immunity Vol. 57, No. 8 ( 1989-08), p. 2542-2546
    In: Infection and Immunity, American Society for Microbiology, Vol. 57, No. 8 ( 1989-08), p. 2542-2546
    Abstract: A cohort of 111 children from Bangui, Central African Republic, was surveyed for enteric Campylobacter infections from birth to the age of 2 years; stools were examined biweekly in these children until 6 months of age and at least four times per year thereafter until 2 years of age and after each diarrheal episode. Blood samples were obtained at birth and at 3, 6, 9, 12, 18, and 24 months of age. Antibodies against glycine-extracted membrane antigens, purified flagella, and cholera toxin (CT) were assayed by an enzyme-linked immunosorbent assay. The results showed that titers of antibody against the three tested antigens increased in children between 6 and 12 months of age and that nearly all children were immunized by the age of 2 years. A significant fall in anti-flagellum (P less than 0.001) and anti-glycine extract antibodies (P less than 0.001) occurred between birth and age 3 months, and children who had Campylobacter infections during the first 6 months of life had significantly (P less than 0.02) less anti-flagellum antibodies at birth than did those who did not have Campylobacter infections during that time. Three-month-interval stratification showed that CT antibody titers at birth were significantly lower in children who developed Campylobacter infection than in controls (P = 0.05). Comparison of the immune response to a single Campylobacter episode showed that 46.6% of children with asymptomatic carriage did not respond to CT while only 5% of children with diarrhea-producing infection did not respond to CT (P less than 0.01), compared with 30% (P = 0.065) and 56% (P less than 0.01), respectively, of the age-matched controls. Antibodies to flagella seem to protect against enteric colonization by Campylobacter jejuni and Campylobacter coli.
    Type of Medium: Online Resource
    ISSN: 0019-9567 , 1098-5522
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    Language: English
    Publisher: American Society for Microbiology
    Publication Date: 1989
    detail.hit.zdb_id: 1483247-1
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  • 7
    In: Blood, American Society of Hematology, Vol. 110, No. 11 ( 2007-11-16), p. 2360-2360
    Abstract: We previously reported an increase of tumor growth inhibition following chemotherapy combined with concomitantly administration of imatinib mesylate [Decaudin D, et al. Int J Cancer2005;113:849–856; Decaudin D, et al. Anti-Cancer drugs2006;17:685–696; Decaudin D, et al. Impact of STI571 on the pharmacokinetics of etoposide and / or ifosfamide in mice. Cancer Res (AACR Annual Meeting) 2006;abstr:5154]. Inversely, combination of imatinib and rituximab was reported in very few cases of patients and remains controversial. In order to explore this particular combination of targeted therapies, we therefore investigated the in vivo impact of rituximab plus imatinib on a B-cell lymphoproliferation. Combination of the tyrosine kinase inhibitor imatinib mesylate (STI571) and the anti-CD20 monoclonal antibody rituximab was evaluated on an EBV-associated B-cell lymphoproliferative disorder xenografted into SCID or Rag2/gc −/− (B-, T-, and NK-) mice. Using SCID mice, we found that STI571 diminished the efficacy of rituximab to inhibit tumor growth in vivo (Figure 1A). Using alymphoid Rag2/gc −/− mice, we showed that the effect of STI571 was not dependent on the presence of NK cells (Figure 1B). In contrast, serum complement administered after STI571 treatment reversed this inhibitory effect. Finally, using non immunodeficient mice, we observed an in vivo decrease of CD4-positive T-cells and mature B-cell lymphocytes after imatinib administration. We found that STI571 decreased the in vivo efficacy of rituximab via serum protein components that could influence complement-dependent cytotoxicity. In contrast, this effect was not dependent on the presence of NK cells. Figure Figure
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
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    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2007
    detail.hit.zdb_id: 1468538-3
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  • 8
    Online Resource
    Online Resource
    American Society of Hematology ; 1977
    In:  Blood Vol. 50, No. 2 ( 1977-08-01), p. 249-258
    In: Blood, American Society of Hematology, Vol. 50, No. 2 ( 1977-08-01), p. 249-258
    Abstract: A high level of fetal hemoglobin was found in an 8-yr-old boy without any hematologic disorders except for a moderate anemia. The absence of hemoglobin abnormalities in the parents led us to suspect a latent malignant disease that, on follow-up, was confirmed to be myelomonocytic leukemia. Hemoglobin biosynthetic studies provided evidence of unbalanced synthesis of globin subunits by reticulocytes, while the production of non-alpha chains was equal to that of alpha chains in bone marrow cells. The expression of red cell antigen i was increased, while those of I, A, and A1 antigens were found to decrease progressively. Two populations of erythrocytes, A-positive and A- negative, were distinguished and could be separated by differential agglutination. Unbalanced globin chain synthesis, increased fetal hemoglobin, and antigenic changes of the membrane were shown to be restricted to the A-negative population. The biologic data were not entirely consistent with a genuine reversion to fetal erythropoiesis. The question remains of a polychromosomal lesion of either quiescent F cells or adult stem cells.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
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    Language: English
    Publisher: American Society of Hematology
    Publication Date: 1977
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  • 9
    Online Resource
    Online Resource
    Oxford University Press (OUP) ; 2008
    In:  Clinical and Experimental Immunology Vol. 82, No. 2 ( 2008-06-28), p. 194-199
    In: Clinical and Experimental Immunology, Oxford University Press (OUP), Vol. 82, No. 2 ( 2008-06-28), p. 194-199
    Abstract: Alterations of imniunological parameters were analysed in patients with advanced malignancies during a phase I trial with rIL-2. Five-day infusions of rIL-2 at doses from 1 × 106 to 24 × 106 biological response modifiers program (BRMP) U/m2 per day were given to 29 patients, with a minimum of three patients per dose. The dose of 24 × 106 U/m2 per day was the maximal tolerated dose (MTD). Immunological parameters were analysed at days 0, 8 and 11 of the rIL-2 courses. Following a leucopenia during rlL-2 infusion, a lymphocytosis was found in all patients except one. The lymphocylosis peaked at day 8 and was detected at doses of rIL-2 as low as 1 × 106 U/m2 per day, reaching a plateau at a dose of 16 × 106 U/m2 per day. Although all lymphocyte subsets were increased in patients receiving rIL-2. some patients had predominant T cells (CD3+, NKH1(CD56)-), others had predominant natural killer (NK) cells (CD3-. NKH1(CD56)+), and yet others showed a mixed profile. A strong induction of cells cytotoxic for K.562 targets was found in all patients at days 8 and 11. Eighteen patients received, 1 month later, a second treatment in which infusion of rIL-2 was preceded by a course of 5 days infusion of 2 × 106 U/m2 per day recombinant interferon-gamma (rIFN-γ)- The infusion of rIFN-γ prior to rIL-2 had no effect on the rIL-2-induced alterations of immunological parameters. Taken together, our results suggest that immune stimulation by rIL-2 occurs even at low doses and is maximal at a dose below the MTD; and that pretreatment with low-dose rlFN-γ does not modify the immune stimulation by rIL-2.
    Type of Medium: Online Resource
    ISSN: 1365-2249 , 0009-9104
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    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2008
    detail.hit.zdb_id: 2020024-9
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  • 10
    Online Resource
    Online Resource
    Elsevier BV ; 1988
    In:  Annales de l'Institut Pasteur / Virologie Vol. 139 ( 1988-1), p. 239-241
    In: Annales de l'Institut Pasteur / Virologie, Elsevier BV, Vol. 139 ( 1988-1), p. 239-241
    Type of Medium: Online Resource
    ISSN: 0769-2617
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    Language: English
    Publisher: Elsevier BV
    Publication Date: 1988
    detail.hit.zdb_id: 2202736-1
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