GLORIA

GEOMAR Library Ocean Research Information Access

Your email was sent successfully. Check your inbox.

An error occurred while sending the email. Please try again.

Proceed reservation?

Export
Filter
  • American Association for Cancer Research (AACR)  (7)
  • 1
    Online Resource
    Online Resource
    American Association for Cancer Research (AACR) ; 2016
    In:  Cancer Research Vol. 76, No. 7_Supplement ( 2016-04-01), p. A52-A52
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 76, No. 7_Supplement ( 2016-04-01), p. A52-A52
    Abstract: This abstract is being presented as a short talk in the scientific program. A full abstract is printed in the Proffered Abstracts section (PR07) of the Conference Proceedings. Citation Format: Mara Gilardi, Simone Bersini, Roger Dale Kamm, Matteo Moretti, Marco Vanoni. Dissection of cancer cells extravasation through human vascularized 3D microfluidic model: The major role of talin-1. [abstract]. In: Proceedings of the AACR Special Conference on Tumor Metastasis; 2015 Nov 30-Dec 3; Austin, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(7 Suppl):Abstract nr A52.
    Type of Medium: Online Resource
    ISSN: 0008-5472 , 1538-7445
    RVK:
    RVK:
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2016
    detail.hit.zdb_id: 2036785-5
    detail.hit.zdb_id: 1432-1
    detail.hit.zdb_id: 410466-3
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
  • 2
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 80, No. 4_Supplement ( 2020-02-15), p. GS4-06-GS4-06
    Abstract: Background. Partial breast irradiation (PBI) is a reasonable alternative for a whole breast irradiation (WBI) in selected early stage breast cancer patients. The 5-year analysis of the APBI IMRT Florence phase 3 trial showed no significant difference in terms of ipsilateral tumor recurrence (IBTR) and survival rates between the two arms. We present the 10-year follow up data. Methods. From March 2005 to June 2013, women aged more than 40 years affected by early BC, with a maximum pathological tumor size of 25 mm, were randomly assigned in a 1:1 ratio to receive either WBI using three-dimensional conformal radiotherapy (3DCRT) or accelerated PBI (APBI) using intensity-modulated radiotherapy (IMRT) technique. Patients in the APBI arm received a total dose of 30 Gy to the tumor bed in five daily fractions. The WBI arm received 50 Gy in 25 fractions, followed by a boost on the tumor bed of 10 Gy in five fractions. The primary end-point, IBTR rate is now assessed at 10 years in the ITT population, as well as secondary endpoints: overall survival (OS), breast cancer specific survival (BCSS), distant metastasis free survival (DMFS), contralateral breast cancer (CBC), and locoregional recurrences (LRR). This trial is registered with ClinicalTrials.gov, number NCT02104895. Results. Of the 520 patients, 260 were enrolled in the APBI-arm and 260 in the WBI-arm; median age was 62.8 years (63.6 in the APBI and 61.6 in the WBI arm, p=0.20). Both treatment-arms achieved a median 10-year follow-up (10.1 in APBI-arm and 10.4 in WBI-arm, p=0.39) and were comparable regarding age, tumor size, grade, tumor type, and adjuvant endocrine treatment. No significant difference in terms of IBTR rates between treatment arms was shown (log rank test p=0.58). In the group who received APBI, the 5-year IBTR was 1.96% (5 events; 95% CI: 0.3;3.7) and the 10-year IBTR was 3.74% (9 events; 95% CI: 1.5;6.3). In the group who received WBI, the 5-year IBTR rate was 1.2% (3 events; 95% CI: 0;2.5) and the 10-year IBTR was 2.5% (6 events; 95% CI: 0.7;4.5). HR for APBI patients compared with WBI patients was 1.33 (p=0.58; 95% CI: 0.49;3.56). There were no significant differences between treatment arms regarding survival outcomes. OS (log rank test p=0.33): APBI 95.4% (95% CI: 93.6;97.2) versus WBI 94.3% (95% CI: 92.3;96.3); HR for APBI patients 0.66 (p=0.33; 95% CI: 0.29;1.53). BCSS (log rank test p=0.55): APBI 98% (95% CI: 96.8;99.2) versus WBI 97.5% (95% CI: 96.2;98.8); HR for APBI patients 0.68 (P=0.55; 95% CI: 0.19;2.42). DMFS (log rank test p=0.45): APBI 97.4% (95% CI: 96.0;98.8) versus WBI 96.1% (95% CI: 94.4;97.8); HR for APBI patients 0.67 (p=0.45; 95% CI: 0.24;1.89). Cumulative incidence estimates of 10-year LRR were 3.9% (95% CI: 2.24;5.56) for APBI versus 3.0% (95% CI: 1.53;4.47) for WBI (log rank test p=0.59). CBC observed after APBI were 5 (1.9%) as compared to 9 (3.5%) after WBI (p=0.42). Conclusion. IBTR rate after 10 years in patients with early breast cancer who were treated with APBI using IMRT technique in 5 fractions is rare and not significantly different from patients treated with WBI. OS, BCSS, DMFS, and LRR control are also comparable. Thus, APBI should be considered a reasonable alternative for a WBI in early breast cancer patients. Citation Format: Icro Meattini, Calogero Saieva, Sara Lucidi, Monica lo Russo, Vieri Scotti, Isacco Desideri, Livia Marrazzo, Gabriele Simontacchi, Monica Mangoni, Carlotta Becherini, Luca Visani, Lisa Paoletti, Erica Moretti, Luca Triggiani, Marco Bernini, Lorenzo Orzalesi, Luis Sanchez, Jacopo Nori, Stefania Pallotta, Simonetta Bianchi, Lorenzo Livi. Accelerated partial breast or whole breast irradiation after breast conservation surgery for patients with early breast cancer: 10-year follow up results of the APBI IMRT Florence randomized phase 3 trial [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr GS4-06.
    Type of Medium: Online Resource
    ISSN: 0008-5472 , 1538-7445
    RVK:
    RVK:
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2020
    detail.hit.zdb_id: 2036785-5
    detail.hit.zdb_id: 1432-1
    detail.hit.zdb_id: 410466-3
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
  • 3
    Online Resource
    Online Resource
    American Association for Cancer Research (AACR) ; 2016
    In:  Cancer Research Vol. 76, No. 7_Supplement ( 2016-04-01), p. PR07-PR07
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 76, No. 7_Supplement ( 2016-04-01), p. PR07-PR07
    Abstract: Cancer cells spread from a primary tumor to secondary loci is responsible for more than 90% of cancer related mortality. Hematogenous metastasis is a complex process [1]. It includes a chain of events that can be summarized as follows: migration from primary tumor site and intravasation of the primary tumor cancer cells into the blood flow, dissemination through the circulation, extravasation in different organs, survival in the new microenvironment and colonization with generation of a new tumor. Recently our group presented a microfluidic 3D model reproducing the effects of the CXCL5-CXCR2 interaction between bone cells and metastatic breast cancer cells observed in vivo [2]. We further developed a human 3D microfluidic model that enables the study of human metastatic breast cancer cell extravasation within a perfusable human microvascularized bone-mimicking microenvironment [3] . Understanding the cellular and molecular events implicated in extravasation could facilitate the design of new therapeutic strategies targeting cancer cells only in order to couple these new developed therapies with already existing treatments and finally fight cancer. Talin-1 is a cytoplasmic adaptor essential for integrin-mediated adhesion to the ECM. Talin-1 links the actin cytoskeleton to integrin at the plasma membrane, regulates the focal adhesion pathway in normal cells and it is up-regulated in triple negative breast cancer cells such as MDA-MB231 and it is mutated in sarcomas. Based on the above described models, we developed a human vascularized 3D microfluidic device where human perfusable capillary like structures were embedded in fibrin matrix, characterized by mature endothelium markers (VE-cadherin, ZO-1) and physiological permeability (1.5±0.76)*10-6cm/s. Since these models can provide quantitative data on cancer cell extravasation, we focused on the role of Talin-1 in extravasation through blood vessels and in early invasion in two cell lines whose Talin-1 expression was silenced by SiRNA: triple negative metastatic breast cancer cells (MDA-MB231) and the metastatic fibro-sarcoma cell line (HT1080). Talin-1 silencing was confirmed by western blotting with specific antibodies. Adhesion to the endothelial wall, extravasation and ensuing migration out from the wall within the extracellular matrix was monitored by means of confocal high resolution real time imaging analyses. We demonstrated that silencing of Talin-1 expression dramatically and in a statistically significant way reduced both the adhesion efficiency and extravasation in both MDA-MB 231 and HT1080. Cell migration was also strongly and statistically reduced by the SiRNA treatment in both analyzed cell lines. In summary, we are the first to dissect the role of Talin-1 in each step of extravasation, demonstrating that targeting this protein could be an effective strategy to block metastasis. These data identify Talin-1 as a promising target for the development of new anti-metastatic therapies based on Talin-1 inhibition. References: [1] Cell 147:275-92 (2011) [2] Biomaterials 35:2454-2461 (2013) [3] Proc Natl Acad Sci U S A 112:214-9 (2015) Citation Format: Mara Gilardi, Simone Bersini, Roger Dale Kamm, Matteo Moretti, Marco Vanoni. Dissection of cancer cells extravasation through human vascularized 3D microfluidic model: The major role of talin-1. [abstract]. In: Proceedings of the AACR Special Conference on Tumor Metastasis; 2015 Nov 30-Dec 3; Austin, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(7 Suppl):Abstract nr PR07.
    Type of Medium: Online Resource
    ISSN: 0008-5472 , 1538-7445
    RVK:
    RVK:
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2016
    detail.hit.zdb_id: 2036785-5
    detail.hit.zdb_id: 1432-1
    detail.hit.zdb_id: 410466-3
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
  • 4
    In: Clinical Cancer Research, American Association for Cancer Research (AACR), Vol. 26, No. 9 ( 2020-05-01), p. 2131-2139
    Abstract: Thymidine kinase 1 (TK1) is downstream to the CDK4/6 pathway, and TK activity (TKa) measured in blood is a dynamic marker of outcome in patients with advanced breast cancer (ABC). This study explores TK1 as a biomarker of palbociclib response, both in vitro and in patients with ABC. Experimental Design: Modulation of TK1 levels and activity by palbociclib were studied in seven estrogen receptor–positive breast cancer cell lines: sensitive (PDS) and with palbociclib acquired resistance (PDR). TKa was assayed in plasma obtained at baseline (T0), after one cycle (T1), and at disease progression on palbociclib (T2) in patients enrolled in the “To Reverse ENDocrine Resistance” (TREnd) trial (n = 46). Results: Among E2F-dependent genes, TK1 was significantly downregulated after short-term palbociclib. Early TKa reduction by palbociclib occurred in PDS but not in PDR cells. In patients, median TKa (mTKa) at T0 was 75 DiviTum units per liter (Du/L), with baseline TKa not proving prognostic. At T1, mTKa decreased to 35 Du/L, with a minority of patients (n = 8) showing an increase—correlating with a worse outcome than those with decreased/stable TKa (n = 33; mPFS 3.0 vs 9.0 months; P = 0.002). At T2, mTKa was 251 Du/L; patients with TKa above the median had worse outcomes on post-study treatment compared with those with lower TKa (2.9 vs 8.7 months; P = 0.05). Conclusions: TK is a dynamic marker of resistance to palbociclib which may lead to early identification of patients in whom treatment escalation may be feasible. In addition, TKa may stratify prognosis in patients with acquired resistance to palbociclib.
    Type of Medium: Online Resource
    ISSN: 1078-0432 , 1557-3265
    RVK:
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2020
    detail.hit.zdb_id: 1225457-5
    detail.hit.zdb_id: 2036787-9
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
  • 5
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 69, No. 6 ( 2009-03-15), p. 2287-2295
    Abstract: Limited information is available concerning the expression and role of microRNAs in prostate cancer. In this study, we investigated the involvement of miR-205 in prostate carcinogenesis. Significantly lower miR-205 expression levels were found in cancer than in normal prostate cell lines as well as in tumor compared with matched normal prostate tissues, with a particularly pronounced reduction in carcinomas from patients with local-regionally disseminated disease. Restoring the expression of miR-205 in prostate cancer cells resulted in cell rearrangements consistent with a mesenchymal-to-epithelial transition, such as up-regulation of E-cadherin and reduction of cell locomotion and invasion, and in the down-regulation of several oncogenes known to be involved in disease progression (i.e., interleukin 6, caveolin-1, EZH2). Our evidence suggests that these events are driven by the concurrent repression of specific predicted miR-205 targets, namely N-chimaerin, ErbB3, E2F1, E2F5, ZEB2, and protein kinase Cε. Strikingly, the latter seemed to play a direct role in regulating epithelial-to-mesenchymal transition. In fact, its down-regulation led to a cell phenotype largely reminiscent of that of cells ectopically expressing miR-205. Overall, we showed for the first time that miR-205 exerts a tumor-suppressive effect in human prostate by counteracting epithelial-to-mesenchymal transition and reducing cell migration/invasion, at least in part through the down-regulation of protein kinase Cε. [Cancer Res 2009;69(6):2287–95]
    Type of Medium: Online Resource
    ISSN: 0008-5472 , 1538-7445
    RVK:
    RVK:
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2009
    detail.hit.zdb_id: 2036785-5
    detail.hit.zdb_id: 1432-1
    detail.hit.zdb_id: 410466-3
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
  • 6
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 64, No. 2 ( 2004-01-15), p. 606-611
    Abstract: The acquisition of the capacity to invade surrounding tissues confers a more malignant phenotype to tumor cells and is necessary for the establishment of metastases. The understanding of the molecular mechanisms underlying cell invasion in human solid tumors such as colorectal cancers could provide not only more sensitive prognostic analyses but also novel molecular targets for cancer therapy. We report in this article that K+ ion channels belonging to the HERG family are important determinants for the acquisition of an invasive phenotype in colorectal cancers. The herg1 gene and HERG1 protein are expressed in many colon cancer cell lines, and the activity of HERG channels modulates colon cancer cell invasiveness. Moreover, the amount of HERG1 protein expressed on the plasma membrane is directly related to the invasive phenotype of colon cancer cells. Finally, both the herg1 gene and HERG1 protein were expressed in a high percentage of primary human colorectal cancers, with the highest incidence occurring in metastatic cancers, whereas no expression could be detected either in normal colonic mucosa or in adenomas.
    Type of Medium: Online Resource
    ISSN: 0008-5472 , 1538-7445
    RVK:
    RVK:
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2004
    detail.hit.zdb_id: 2036785-5
    detail.hit.zdb_id: 1432-1
    detail.hit.zdb_id: 410466-3
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
  • 7
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 77, No. 13_Supplement ( 2017-07-01), p. 5814-5814
    Abstract: In extravasation cancer cells and vascular niche are involved in a tight cross-talk which has been defined as the rate-regulating event for metastases establishment [1]. Recent, animal studies support the hypothesis that metastatic deficiency lies in focal adhesion complex alterations, however, it still needs to be elucidated which are the specific regulators of each event composing extravasation. Focal adhesion proteins Talin-1 (TLN-1) and Focal Adhesion Kinase (FAK) are up-regulated in breast cancer. Both targets due to their structural and functional role, dramatically influence cancer mechanotransduction leading to endothelial junction disruption, critical in extravasation process [2] . Here, we generated ad hoc engineered models for each extravasation step allowing single cell behavior analyses through high resolution real time imaging in a reliable and quantitative way in a physiological environment. Through this novel approach we analyzed the effect of TLN-1 and FAK and their genetic and chemical inhibition in breast cancer extravasation. The 3D-microfluidic vasculature displayed maturation markers and physiological permeability (1.5±0.76*10-6cm/s) and allowed cancer cell injection through the hollow vessels. Western blot confirmed TLN-1 and FAK knock down (KD) in MDA-MB231. Both targets significantly affected morphology and proliferation (p & lt;0.001). We demonstrated the involvement of both targets in adhesion to the endothelium (p & lt;0.001). Trans endothelial migration (TEM) was decreased in TLN-1 KD (p & lt;0.05) and in FAK KD (P & lt;0.01). Both TLN-1 and FAK KD cells were trapped into the vessels and were not able to extend pseudopodia. Cancer migration tracking in 3D matrix was statistically lower in both KD (p & lt;0.001). The calculated ratios of adhesion/TEM and invasion/TEM were lower in TLN-1 compared to FAK KD, demonstrating that TLN-1 plays a major role in adhesion to endothelium and early invasion while FAK was identified as the main driver in TEM. Additive (TLN-1 and FAK) KD did not show significant difference respect to the target that mostly affected adhesion and invasion demonstrating TLN-1 role in these events. Additive KD was statistically lower compared to TLN-1 KD (P & lt;0.05), supporting FAK crucial role in TEM. Inhibition of TLN-1 and FAK phosphorylation revealed that actin polymerization and pseudopodia formation (required for extravasation) were dependent by their structural role and were independent by their phosphorylation. However, the inhibition of FAK activity showed FAK phosphorylation as the key driver of TEM mechanism (p & lt;0.01). Concluding, our results supported by in vivo data (p & lt;0.05) showed that TLN-1 and FAK inhibition may represent novel strategies challenging mechanisms leading to metastatic establishment. 1. Cell,2011.147(2):p.275-92; 2. Proc Natl Acad Sci USA,2015.112(1):p.214-9 Citation Format: Mara Gilardi, Simone Bersini, Rosa Maria Moresco, Marco Vanoni, Roger D. Kamm, Matteo Moretti. Engineered microfluidic 3D human microvasculature identifies Talin-1-dependent adhesion and FAK activation as the key promoter of cancer cell trans-endothelial migration [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 5814. doi:10.1158/1538-7445.AM2017-5814
    Type of Medium: Online Resource
    ISSN: 0008-5472 , 1538-7445
    RVK:
    RVK:
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2017
    detail.hit.zdb_id: 2036785-5
    detail.hit.zdb_id: 1432-1
    detail.hit.zdb_id: 410466-3
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
Close ⊗
This website uses cookies and the analysis tool Matomo. More information can be found here...