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  • 1
    Online Resource
    Online Resource
    American Association for Cancer Research (AACR) ; 2009
    In:  Cancer Research Vol. 69, No. 24_Supplement ( 2009-12-15), p. 4171-4171
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 69, No. 24_Supplement ( 2009-12-15), p. 4171-4171
    Abstract: The development of aromatase inhibitors has provided novel therapeutic strategies for post-menopausal patients with estrogen receptor positive (ER+) breast tumors. Aromatase inhibitors, such as letrozole, inhibit ER+ breast cancer cell growth by blocking the synthesis of estrogen by the enzyme aromatase in the tumor stroma. However, ER+ breast cancer cases can sometimes fail or cease to benefit from such therapy. Several mechanisms have been proposed for aromatase inhibitor resistance. Here, we investigate the role of the 88 kDa autocrine growth factor PC-Cell Derived Growth Factor, also known as GP88 or progranulin on the acquisition of aromatase inhibitors resistance by ER+ breast cancer cells. GP88 is the largest member of the epithelin-granulin family characterized by a unique cysteine rich motif. GP88 has been shown to play a role in breast tumorigenesis. GP88 expression increased in breast cancer cells in a positive correlation with tumorigenesis whereas inhibition of GP88 expression lead to a 98% reduction in tumor incidence and growth rate in vivo. Pathological studies of paraffin embedded breast cancer biopsies have shown that GP88 is expressed in infiltrating ductal carcinoma (IDC) in correlation with expression of parameters of poor prognosis but was independent from Her-2 expression. Most importantly, increased GP88 expression in ER+ IDC was associated with increased recurrence and decreased overall survival. The present study investigated the effect of GP88 on the proliferation and letrozole responsiveness of ER+ breast cancer cells that express high aromatase activity (MCF-7 CA and MCF-7 AC1 cells). For both cell types, GP88 added exogenously conferred letrozole resistance in a time and dose-dependent fashion. GP88 also stimulated survival and soft agar colony formation of MCF-7-CA and AC1 cells in the presence of letrozole. GP88 overexpressing cells displayed higher basal levels of phosphorylated ERK1/2 and AKT, both known to be activated in GP88 mitogenic signaling pathways. In addition, naturally letrozole resistant breast tumors displayed a 10-fold increase in GP88 expression when compared to letrozole sensitive cells. Treatment of these letrozole resistant cells with GP88 SiRNA lead to a dose dependent inhibition of proliferation and restoration of letrozole sensitivity indicating that GP88 is regulating the ability of the cells to respond to letrozole.These data show the importance of GP88 as a target for the development of diagnostic and therapeutic products for aromatase inhibitor resistant breast cancer. Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 4171.
    Type of Medium: Online Resource
    ISSN: 0008-5472 , 1538-7445
    RVK:
    RVK:
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2009
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  • 2
    In: Alimentary Pharmacology & Therapeutics, Wiley, Vol. 46, No. 3 ( 2017-08), p. 310-321
    Abstract: Linked Content This article is linked to Speight and Mansfield papers. To view this article visit https://doi.org/10.1111/apt.14215 .
    Type of Medium: Online Resource
    ISSN: 0269-2813 , 1365-2036
    URL: Issue
    Language: English
    Publisher: Wiley
    Publication Date: 2017
    detail.hit.zdb_id: 2003094-0
    SSG: 15,3
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  • 3
    In: Journal of Crohn's and Colitis, Oxford University Press (OUP), Vol. 13, No. Supplement_1 ( 2019-01-25), p. S476-S477
    Type of Medium: Online Resource
    ISSN: 1873-9946 , 1876-4479
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2019
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  • 4
    Online Resource
    Online Resource
    Oxford University Press (OUP) ; 2023
    In:  Journal of Crohn's and Colitis Vol. 17, No. Supplement_1 ( 2023-01-30), p. i166-i167
    In: Journal of Crohn's and Colitis, Oxford University Press (OUP), Vol. 17, No. Supplement_1 ( 2023-01-30), p. i166-i167
    Abstract: While the effect of anti-TNFs on postoperative outcomes in patients with Crohn’s disease (CD) has been widely studied, the impact of vedolizumab and ustekinumab on the risk of postoperative complications remains poorly known. Methods All consecutive patients who underwent intestinal resection for CD between July 2014 and April 2022 within 22 French centers were included in a retrospective cohort. The risk of early post-operative complications (≤30days) in patients exposed to biologics was compared to patients not exposed by logistic regression and propensity score-matched analysis adjusted for age, previous intestinal resection, corticosteroids or immunosuppressants exposure, disease activity, presence of abscess, urgent surgery and initial stoma (preoperative contra-indication to anastomosis). Results Among the 1201 patients included, respectively 491 (41%), 76 (6.3%) and 57 (4.7%) were exposed to anti-TNFs, ustekinumab, or vedolizumab within six months before surgery. A total of 317 (26.4%) patients had at least one complication of which 123 (38%) were considered as severe (DINDO III/IV). New surgery was necessary in 69 (5.7%) patients and secondary stoma in 23 (1.9%). Three deaths were observed (0.25%). The rates of overall complications in patients not exposed to biologics, exposed to anti-TNFs, ustekinumab or vedolizumab were respectively 26.1%, 25.1%, 34.7% and 29.8%. The risks of intra-abdominal infectious complications in these four groups were respectively 13.5%, 11.1%, 13.3% and 8.8%. In multivariate analysis, age [OR, 1.02 (1.01-1.04); p=0.004], disease activity [OR, 8.36 (1.79 – 149); p=0.037] , the presence of an abscess [OR, 2.01 (1.25-3.20); p=0.004] and initial stoma [OR, 1.70 (1.10 –2.61); p=0.016] were significantly associated with intra-abdominal infectious complications. Conversely, preoperative enteral nutrition [OR, 0.12 (0.01 -0.59); p=0.040] was associated with a reduction in this risk. Exposure to anti-TNFs [OR, 0.80 (0.51-1.24); p=0.31] , ustekinumab [OR, 1.17 (0.39-3.51); p=0.78] and vedolizumab [OR, 1.28 (0.32-5.17); p=0.72] within the 3 months before surgery were not associated with the risk of intra-abdominal infectious complications. Similar results were observed in patients exposed to these treatments in the month before surgery. Conclusion In this large cohort, a quarter of patients operated on for CD presented an early postoperative complication and 10% a severe complication. Preoperative exposure to anti-TNFs, vedolizumab or ustekinumab was not associated with an increased risk of early postoperative complications. Preoperative enteral nutrition was associated with a reduced risk of intra-abdominal infectious complication.
    Type of Medium: Online Resource
    ISSN: 1873-9946 , 1876-4479
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2023
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  • 5
    In: Journal of Crohn's and Colitis, Oxford University Press (OUP), Vol. 14, No. Supplement_1 ( 2020-01-15), p. S337-S338
    Abstract: The multiplication of therapeutic options with close efficacy and safety, leads to consider acceptability of treatment regimen as a key point for therapeutic decision in inflammatory bowel disease (IBD). We aimed to compare acceptability of IBD treatment regimen and to identify its associated factors. Methods From a nationwide prospective study conducted in 24 public or private centres, IBD patients were consecutively included for 6 weeks. A dedicated questionnaire was developed, tested and validated for the study. It was administered to each included patient and his/her related physician. Acceptability was graded with an acceptability numerical scale (ANS) from 0 (absolutely not acceptable) to 10 (totally acceptable). Results Overall, 1850 patients were included (65.9% with Crohn’s disease (CD), mean age = 41.0 ± 14.7, 22.2% experiencing IBD flare at inclusion). The medications at inclusion were none in 9.0%, oral (PO) monotherapy in 17.3%, subcutaneous (SC) injections in 29.2% and intra-venous (IV) infusions in 44.5% of the patients. The ANS were 8.68 ± 2.52 for PO, 7.67 ± 2.94 for SC and 6.79 ± 3.31 for IV (p & lt; 0.001 for each comparison). The patients reported PO, SC and IV as their first choice in 65.8%, 21.4% and 12.8%, respectively. The reasons for reduced acceptability were the need to come to the hospital (63.0%) for IV infusion, none for SC injections and the fear to forget to take pills (30.5%), the number of daily dose (28.4%) and daily medication as a reminder of disease every day (24.8%) for PO therapy. In multivariable analyses, the following factors were associated with a better acceptability of IV infusion (current IBD flare: p = 0.003 and current IV therapy for IBD: p & lt; 0.001), SC injections (Private practice: p = 0.006 and current SC injections for IBD: p & lt; 0.001) and PO medication (male gender: p = 0.018, higher studies level: p & lt; 0,001 and current oral medication: p = 0.002). The mean ANS for all IBD treatment regimen were compared in the 1850 patients (Figure 1). No difference was observed between CD and UC. In biologics-naïve patients (n = 315), the treatment regimens were ranked in the following order: PO once daily (8.8 ± 2.2), SC/12 weeks (week) (7.9 ± 3.0), SC/8 week and PO twice daily (7.2 ± 3.2 et 6.9 ± 3.4; ns), SC/4 week (6.2 ± 3.4), SC/2 week et IV/8 week (5.1 ± 3.4 and 5.0 ± 3.5; ns)(p & lt; 0.001 except if ns was mentioned). For the patients, the acceptable loss of efficacy to receive a more convenient medication was 5.2% (non-inferiority trial limit). Conclusion While PO administration was preferred by most of IBD patients, the acceptability of treatment regimen is highly impacted by the interval between two doses and the previous medications. Our data could be helpful to guide therapeutic decision in daily practice in IBD.
    Type of Medium: Online Resource
    ISSN: 1873-9946 , 1876-4479
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2020
    detail.hit.zdb_id: 2389631-0
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  • 6
    In: Journal of Crohn's and Colitis, Oxford University Press (OUP), Vol. 13, No. Supplement_1 ( 2019-01-25), p. S316-S316
    Type of Medium: Online Resource
    ISSN: 1873-9946 , 1876-4479
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2019
    detail.hit.zdb_id: 2389631-0
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  • 7
    In: Digestive and Liver Disease, Elsevier BV, ( 2024-1)
    Type of Medium: Online Resource
    ISSN: 1590-8658
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2024
    detail.hit.zdb_id: 2061359-3
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  • 8
    In: Journal of Crohn's and Colitis, Oxford University Press (OUP), Vol. 17, No. Supplement_1 ( 2023-01-30), p. i572-i572
    Abstract: Breast cancer is the most common malignancy observed in patients with inflammatory bowel diseases (IBD) unrelated to the disease or its treatment (Poullenot F et al. JCC 2022). The main aim of our study was to assess the risk of incident cancer according to the IBD treatment given in patients with prior breast cancer. Methods Consecutive IBD patients with prior breast cancer diagnosis were included in a multicenter retrospective cohort from 25 tertiary centres. Inclusion date corresponded to the diagnosis of index cancer. Follow up was calculated from the first administration of immunomodulator after cancer diagnosis (or cancer diagnosis date in absence of treatment) to the occurrence of incident cancer, corresponding to recurrence of breast cancer or de novo cancer, or to the last follow-up visit. Patients were categorized according to the use or not of immunomodulator after cancer diagnosis: thiopurines, methotrexate, anti-TNF, vedolizumab, ustekinumab. Crude incidence rates were compared between patients receiving at least one immunomodulator and those without immunomodulator before and after matching on age, lymph node, and metastasis extension and tumor’s grade, using a propensity-score analysis with a 1:1 ratio. Results Among the 151 identified patients, 80 patients with full available data were analyzed: 76 (95%) women; mean age at index cancer diagnosis: 51.5 years [standard deviation (SD): 11.5 years]; 44 (55%) with Crohn’s disease, 35 (44 %) ulcerative colitis and 1 (1 %) indeterminate colitis; median IBD duration at inclusion was 13 years [interquartile range (IQR) 6-21] . After a median follow up of 84 months [IQR 49-154], 16 (20%) incident cancers were observed: 12 (15%) recurrences and 4 (5%) cancer de novo. Three (4%) patients died from cancer related cause during the follow up. 39 (49%) patients received no immunomodulator and, 11 (14%) were treated with thiopurines, 6 (7.5%) with methotrexate, 18 (22.5%) with anti-TNF, 5 (6%) with vedolizumab and one (1%) with ustekinumab. Those treatments were initiated with a median interval of 24 months [IQR 7-48] after cancer diagnosis. Crude incidence rate per 1000 person-years were 47.97 for patients not exposed to any immunomodulator and 12.61 for the others (p=0.0248). After matching, adjusted crude incidence rates per 1000 person-years were 50 and 27.27, respectively (p=0.3798). Rates of survival without incident cancer were not different between the two groups after matching on age, lymph node, metastasis extension, and tumor’s grade (p=0.17) (Figure 1). Conclusion In the present multicenter retrospective cohort, incident cancer risk among patient with IBD and prior breast cancer was not increased in patients subsequently exposed to immunomodulators.
    Type of Medium: Online Resource
    ISSN: 1873-9946 , 1876-4479
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2023
    detail.hit.zdb_id: 2389631-0
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  • 9
    In: Journal of Crohn's and Colitis, Oxford University Press (OUP), Vol. 16, No. Supplement_1 ( 2022-01-21), p. i222-i223
    Abstract: In the context of the Sars-Cov2 pandemic, the management of patients with chronic diseases and/or receiving immunosuppressive drugs was of concern due to lack of data to dictate their management. The objectives of our study were to evaluate the characteristics and prognosis of COVID-19 among IBD patients and to study the factors associated with severe COVID-19. Methods We carried out a multicentre bispective study in 30 French GETAID centres. Participating centres were asked to report all consecutive COVID19 cases occurring in their IBD-cohort between March,1st and December,31st 2020. The cases had to be confirmed by a PCR test, or by a chest CT scan demonstrating COVID19 lesions. In addition to the baseline examination, patients were scheduled for a follow up visit within 3–6 months following their infection. Demographics, disease characteristics, treatments, and the clinical course of IBD were prospectively recorded. Severe COVID-19 was defined as admission to the hospital & gt;1 day and/or use of oxygen therapy and/or death. Predictive factors for developing severe COVID-19 were explored using univariate and multivariate logistic regression. Results A total of 719 IBD patients with COVID 19 were included; 54.2% were women, median age was 42 years, 64.4% had Crohn’s disease (CD), and median disease duration was 10.8 years. 13.3% of the patients were active smokers;12.7% had a BMI & gt;30. With respect to the treatment, 72(10%) patients were not on any IBD medication, 75(10.4%) were only receiving 5-ASA, 164(22.8%) received conventional immunosuppressants, and 509(70.8%) biologics.21.6% of the patients developed either diarrhoea in remitters, or an exacerbation of diarrhoea in active patients. IBD treatments were maintained unchanged, suspended or discontinued in 73.4%, 25.5%, and 1.1% of the patients. Over the follow-up period, 13.2% of the patients had a flare. A total of 68 patients developed severe COVID 19, 67(9.3%) were hospitalized for a median duration of 6 days, and 4(0.6%) patients died. In multivariate analysis, age & gt; 50 years (OR: 2.0,CI:1.06–3.72; p=0.031), obesity (OR: 2.01,CI:1.05–4.09; p=0.037), and comorbidities (OR: 3.28,CI:1.76–6.09; p=0.0002) were factors associated with the occurrence of severe COVID 19; while immunomodulatory treatment (biologic and/or immunosuppressant) was a protective factor for developing severe COVID 19 (OR: 0.38,CI: 0.22–0.69; p=0.0012). Conclusion Rate of severe COVID 19 in this cohort of IBD patients was corresponding to the general population with similar risk factors for severity, i.e., age, obesity and comorbidities. Prescription of immunomodulators was protective against severe COVID 19, raising the hypothesis of their potential immunological effect on the immune storm phase of Sars-Cov2.
    Type of Medium: Online Resource
    ISSN: 1873-9946 , 1876-4479
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2022
    detail.hit.zdb_id: 2389631-0
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  • 10
    In: Journal of Crohn's and Colitis, Oxford University Press (OUP), Vol. 12, No. supplement_1 ( 2018-01-16), p. S408-S408
    Type of Medium: Online Resource
    ISSN: 1873-9946 , 1876-4479
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2018
    detail.hit.zdb_id: 2389631-0
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