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See detailImpacts of Ionizing Radiation on the Different Compartments of the Tumor Microenvironment
Leroi, Natacha ULg; LALLEMAND, François ULg; COUCKE, Philippe ULg et al

in Frontiers in Pharmacology (2016), 7

During the last decade, the initial cancer cell-centered view of tumors has greatly evolved to an integrated vision of tumor biology taking into account the key contribution of the TME. Obviously, the ... [more ▼]

During the last decade, the initial cancer cell-centered view of tumors has greatly evolved to an integrated vision of tumor biology taking into account the key contribution of the TME. Obviously, the different compartments of TME are closely related and contribute not only to tumor progression, but also to its response to treatments. Importantly, the TME evolves over time during the different steps of cancer development and is also affected by different therapeutic modalities. Although, improvements have been achieved regarding RT delivery to the primary tumor, ionizing radiation also target nontumor cells that influence tumor growth and metastatic dissemination. Different approaches have been proposed to overcome the radioresistance of cancer cells. The TME-mediated radioresistance is now the object of researches, which has been elegantly reviewed recently by Barker et al. (2015) and severalarticles pointed out the importance of treatments that modify the TME and likely radiosensitize tumor (Ansiaux et al., 2005; Crokart et al., 2005b; Frérart et al., 2008). However, the impact of anti-cancer treatments on the TME and consequently on the tumor phenotype, response to treatment and metastases, is often neglected. Here we pointed out the impact of RT on the TME. Recent findings emphasize the interest to optimize RT (i.e., dose per fraction) and timing of surgery (Leroi et al., 2015; Surace et al., 2015) in order to prevent metastatic spreading. The future challenge in RT will be to define the most appropriate combinations between RT, and other therapeutic modalities with the optimal sequence and timing of treatments. In this context, investigation of the TME-related acquired resistance will be essential and will provide important innovative data. [less ▲]

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See detailFeasibility study of repetitive diffusion MRI after Neoadjuvant radiotherapy for following tumor microenvironment.
LALLEMAND, François ULg; Leroi, Natacha ULg; Bahri, Mohamed Ali ULg et al

Conference (2016, March 22)

Purpose/Objective. Neoadjuvant radiotherapy (NeoRT) improves tumor local control and tumor resection in many cancers. The timing between the end of the NeoRT and surgery is mostly driven by the occurrence ... [more ▼]

Purpose/Objective. Neoadjuvant radiotherapy (NeoRT) improves tumor local control and tumor resection in many cancers. The timing between the end of the NeoRT and surgery is mostly driven by the occurrence of side effects or the tumor downsizing. We previously demonstrated in an in vivo model that the timing of surgery and the schedule of NeoRT influenced the tumor dissemination. Here, our aim is to evaluate with functional MRI (fMRI) the impact of the radiation treatment on the tumor microenvironment and subsequently to identify non-invasive markers helping to determine the best timing to perform surgery for avoiding tumor spreading. First, we needed to demonstrate the feasibility of repetitive MRI imaging after NeoRT in mice. Material/methods. We used two models of NeoRT we previously developed in mice: MDA-MB 231 and 4T1 cells implanted in the flank of mice. When tumors reached the planned volume, they are irradiated with 2x5 Gy and then surgically removed at different time points after RT. In the mean time between the end of RT and the surgical procedure, mice were imaged in a 9,4T Agilent® MRI. Diffusion Weighted (DW) -MRI was performed every 2 days between RT and surgery. For each tumors we acquired 8 slices of 1 mm thickness and 0.5 mm gap with an “in plane voxel resolution” of 0.5 mm. For DW-MRI, we performed FSEMS (Fast Spin Echo MultiSlice) sequences, with 9 different B-values (from 40 to 1000) and B0, in the 3 main directions. We also performed IVIM (IntraVoxel Incoherent Motion) analysis, in the aim to obtain information on intravascular diffusion, related to perfusion (F: perfusion factor) and subsequently tumor vessels perfusion. Results. As preliminary results, with the MBA-MB 231 we observed a significant increase of F at day 6 after irradiation than a decrease and stabilization until surgery. No other modifications of the MRI signal, ADC, D or D* were observed. We observed similar results with 4T1 cells, F increased at day 3 than returned to initial signal. The difference in the timing of the peak of F can be related to the difference in tumor growth between MBA-MB 231 and 4T1 (four weeks vs one week). Conclusion. For the first time, we demonstrate the feasibility of repetitive fMRI imaging in mice models after NeoRT. With these models, we show a significant peak of the perfusion factor (F) at day 6 or day 3. This change occurs between the two previous time points of surgery demonstrating a difference in the metastatic spreading. Indeed, after a NeoRT of 2X5Gy we observed more metastases in the lung when MDA-MB 231 tumor bearing mice are operated 4 days after RT compared to 11 days. These preliminary results are very promising for identifying noninvasive markers for determining the best timing for surgery. [less ▲]

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See detailOsteopontin predicts radiotherapy response of glioblastoma patients : new role in DNA damage repair
Henry, Aurélie ULg; Nokin, Marie-Julie; Leroi, Natacha ULg et al

Conference (2016, March 22)

- Introduction: Glioblastoma (GBM) is the most aggressive and common solid human brain tumor. Because of GBM heterogeneity, location and aggressiveness, none of the available treatment is curative. These ... [more ▼]

- Introduction: Glioblastoma (GBM) is the most aggressive and common solid human brain tumor. Because of GBM heterogeneity, location and aggressiveness, none of the available treatment is curative. These treatments include maximal surgical resection, radiotherapy and concomitant or adjuvant chemotherapy with Temozolomide. However, the prognosis of adult patients with GBM remains poor and the survival outcome after treatment does not exceed 15 months. GBM-composing cells have developed many strategies to counteract these current therapies. Among the wide hallmarks acquired to survive, high osteopontin (OPN) expression correlates with lower overall and disease-free/relapse-free survival in all tumors combined, as well in brain cancer. Our recent study (Lamour V and Henry A, IJC 2015) has demonstrated the role of OPN in the tumorigenicity of glioblastoma cells and its importance in the maintenance of the stem characters. In the continuation of this work, our recent studies focused on the potential role of OPN in the resistance of GBM cells to radiotherapy and its potential implication in the initiation of Double Strand Breaks (DSBs) repair mechanisms. - Aims: In the context of this study, different GBM cell lines (U251-MG, U87-MG and U87 Viii) were used to assess the role of OPN in the initiation of the DSBs repair mechanism after an exposure to gamma-irradiation. - Methods and results: We performed the transient transfection of different GBM cell lines (U251-MG, U87-MG and U87-MG overexpressing EGFR VIII) with siRNAs specifically directed against OPN. After irradiation, all these OPN-depleted cells consistently showed a lower induction of γ–H2AX compared to control (irrelevant siRNA) as evidenced by western blot and immunofluorescence techniques. Thereafter, clonogenic assays allowed to prove that the survival of OPN-depleted cells was affected after an exposure to irradiation. To assess the importance of OPN expression in the response to radiotherapy, an heterotopic xenograft model was used. In brief, IPTG-inducible U87 shOPN clones were injected subcutaneously in NOD-SCID mice and were allowed to form a tumor. When average tumor volume reached a predetermined size range, mice were treated (or not) with IPTG by intraperitoneal injection during five days. At the end of the treatment, tumors were selectively exposed to gamma-irradiation by using a small animal irradiator X-RAD 225Cx (Precision X-Ray Inc., North Branford, CT). One week later, mice were sacrificed and tumors were measured. In this pilot study, we observed that mice in which the tumor was depleted in OPN displayed a slight regression in the tumor growth compared to mice that received radiotherapy alone (no IPTG), where the tumor volume remained constant. - Conclusions: Taken together, these preliminary data meet the fact that OPN is important in the response of GBM to radiotherapy. The in vitro results converge to the fact that OPN might be implicated in the initiation of the DSBs repair following irradiation. Currently, we would like to investigate this hypothesis in vivo but also to check the effect of OPN depletion combined to radiotherapy on the survival of mice in an orthotopic xenograft model. [less ▲]

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See detail[18F]FPRGD2 PET/CT imaging of integrin αvβ3 levels in patients with locally advanced rectal carcinoma
WITHOFS, Nadia ULg; Martinive, Philippe ULg; VANDERICK, Jean ULg et al

in European journal of nuclear medicine and molecular imaging (2016)

PURPOSE: Our primary objective was to determine if [18F]FPRGD2 PET/CT performed at baseline and/or after chemoradiotherapy (CRT) could predict tumour regression grade (TRG) in locally advanced rectal ... [more ▼]

PURPOSE: Our primary objective was to determine if [18F]FPRGD2 PET/CT performed at baseline and/or after chemoradiotherapy (CRT) could predict tumour regression grade (TRG) in locally advanced rectal cancer (LARC). Secondary objectives were to compare baseline [18F]FPRGD2 and [18F]FDG uptake, to evaluate the correlation between posttreatment [18F]FPRGD2 uptake and tumour microvessel density (MVD) and to determine if [18F]FPRGD2 and FDG PET/CT could predict disease-free survival. METHODS: Baseline [18F]FPRGD2 and FDG PET/CT were performed in 32 consecutive patients (23 men, 9 women; mean age 63 +/- 8 years) with LARC before starting any therapy. A posttreatment [18F]FPRGD2 PET/CT scan was performed in 24 patients after the end of CRT (median interval 7 weeks, range 3 - 15 weeks) and before surgery (median interval 4 days, range 1 - 15 days). RESULTS: All LARC showed uptake of both [18F]FPRGD2 (SUVmax 5.4 +/- 1.5, range 2.7 - 9) and FDG (SUVmax 16.5 +/- 8, range 7.1 - 36.5). There was a moderate positive correlation between [18F]FPRGD2 and FDG SUVmax (Pearson's r = 0.49, p = 0.0026). There was a moderate negative correlation between baseline [18F]FPRGD2 SUVmax and the TRG (Spearman's r = -0.37, p = 0.037), and a [18F]FPRGD2 SUVmax of >5.6 identified all patients with a complete response (TRG 0; AUC 0.84, 95 % CI 0.68 - 1, p = 0.029). In the 24 patients who underwent a posttreatment [18F]FPRGD2 PET/CT scan the response index, calculated as [(SUVmax1 - SUVmax2)/SUVmax1] x 100 %, was not associated with TRG. Post-treatment [18F]FPRGD2 uptake was not correlated with tumour MVD. Neither [18F]FPRGD2 nor FDG uptake predicted disease-free survival. CONCLUSION: Baseline [18F]FPRGD2 uptake was correlated with the pathological response in patients with LARC treated with CRT. However, the specificity was too low to consider its clinical routine use. [less ▲]

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See detailOsteopontin as a new target in glioblastoma progression and resistance to radiotherapy
Henry, Aurélie ULg; Bellahcene, Akeila ULg; Castronovo, Vincenzo ULg et al

Conference (2015, September 10)

Glioblastoma (GBM) is the most aggressive and common solid human brain tumor. Because of GBM heterogeneity, location and aggressiveness, none of the available treatment is curative. These treatments ... [more ▼]

Glioblastoma (GBM) is the most aggressive and common solid human brain tumor. Because of GBM heterogeneity, location and aggressiveness, none of the available treatment is curative. These treatments include maximal surgical resection, radiotherapy and concomitant or adjuvant chemotherapy with Temozolomide (TMZ). However, the prognosis of adult patients with GBM remains poor and the survival outcome after treatment does not exceed 15 months. Glioblastoma-composing cells have developed many strategies to counteract these current therapies. Among the wide hallmarks acquired to survive, osteopontin (OPN) ranks correlates with lower overall and disease-free/relapse-free survival in all tumors combined, as well in brain cancer. OPN expression is largely considered as a molecular cancer marker associated with poor prognosis for patients with cancer. Our preliminary works (Lamour V and Henry A, IJC 2015) have demonstrated the role of OPN in the tumorigenicity of glioblastoma cells and its importance in the maintenance of the stem charachters. Within the continuance of this work, our recent studies focused on the potential role of OPN in the resistance of glioblastoma cells to radiotherapy and its implication in the initiation of Double Strand Breaks (DSBs) repair mechanism. In this context, U251-MG and U87-MG cells were used to assess the role of OPN in the initiation of the DSBs repair mechanism after an exposure to gamma-irradiation (γ–IR). The transient transfection of both cell lines with siRNA directed against OPN shown a lower induction of γ–H2AX compared to control (irrelevant siRNA). The survival of U251-OPN depleted cells was also affected after an exposure to γ–IR (based on clonogenic assays). However, the sole depletion of OPN in U87 cells affected their survival (independently of the γ–IR). To prove that the secreted form of OPN is necessary to survive after γ–IR, conditionned medium of U87-shSCR clones (rich in OPN) was used to treat U87shOPN clones before an exposure to γ–IR. By immunofluorescence, we observed that the γ–H2AX staining was higher in U87 shOPN clones than when treated with their own conditionned medium (poor in OPN). Currently, we are investigating the in vivo implication of OPN in the initiation of DSBs repair mechanism after an exposure of mice to γ–IR (whole brain exposure). For this purpose, IPTG-inducible U87 shRNA clones (SCR and OPN) have been generated and validated for an orthotopic xenograft model in NOD-SCID mice. The survival after a radiotherapy of 10 Gy (2Gy per day for 5 days) will be assessed in OPN-positive and –negative tumor-bearing mice. Taken together, these datas suggest that OPN could represent an important pronostic factor for patient response to radiotherapy in the context of GBM. [less ▲]

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See detailFunctional MRI for predicting metastatic spreading at the time of surgery after neoadjuvant radiotherapy
LALLEMAND, François ULg; Leroi, Natacha ULg; Bahri, Mohamed Ali ULg et al

Poster (2015, April)

Neoadjuvant radiotherapy (NeoRT) improves tumor local control and tumor resection in many cancers. The timing between the end of the NeoRT and surgery is driven by the occurrence of side effects or the ... [more ▼]

Neoadjuvant radiotherapy (NeoRT) improves tumor local control and tumor resection in many cancers. The timing between the end of the NeoRT and surgery is driven by the occurrence of side effects or the tumor downsizing. Some studies demonstrated that the timing of surgery and the RT schedule could influence tumor dissemination and subsequently patient overall survival. Our aim is to evaluate with functional MRI the impact of the radiation treatment on the tumor microenvironment and subsequently to determine the best timing to perform surgery for avoiding tumor spreading. [less ▲]

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See detailIdentification of predictive markers based on functional imaging of metastatic spreading at the time of surgery after neoadjuvant radiotherapy
LALLEMAND, François ULg; Leroi, Natacha ULg; Bahri, Mohamed Ali ULg et al

Poster (2015, January 27)

Neoadjuvant radiotherapy (NeoRT) improves tumor local control and tumor resection in many cancers. The timing between the end of the NeoRT and surgery are driven by the occurrence of side effects or the ... [more ▼]

Neoadjuvant radiotherapy (NeoRT) improves tumor local control and tumor resection in many cancers. The timing between the end of the NeoRT and surgery are driven by the occurrence of side effects or the tumor downsizing. Some studies demonstrated that the timing of surgery and the RT schedule could influence tumor dissemination. Our aim is to evaluate with functional MRI the impact of the radiation treatment on the tumor microenvironment and subsequently to determine the best timing to perform surgery. We used a model of NeoRT, 4T1 cells were implanted in the flank of BalbC mice. Seven days after, tumors were irradiated with 2x5Gy than we surgically removed this lesion 11 days after RT. Diffusion Weighted (DW) and Dynamic Contrast Enhancement (DCE) -MRI was performed every 2 days during 11 days between RT and surgery. We developed a homemade “portacath” specifically dedicated for mice and for repetitive I.V. contrast agent injection. For DW-MRI, we performed sequences with 10 different B-value to achieve IntraVoxel Incoherent Motion analysis. For DCE-MRI, we used FSEMS sequence for keeping the same slices as with DW-MRI. For both images, we performed analysis on the entire tumor volume. We obtained very promising preliminary results showing good uniformity in the ADC (Attenuation Diffusion Coefficient). We succeeded to follow mice with imaging during the 11 days without major troubles. We observed less variability of the ADC signal during the 11 days in the irradiated tumors compared to the control. The signal to noise ratio was relatively poor for the diffusion sequence and need to be improved. For the first time, we demonstrate the feasibility of repetitive MRI functional imaging in a mice model of NeoRT. These results open perspectives for studying modifications of the tumor microenvironment induced by neoadjuvant RT. The techniques need to be improved and correlated to the tumor dissemination in function of the RT schedule and timing of surgery. [less ▲]

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See detailAdult mouse sub-ventricular zones stimulate glioblastoma stem cells specific invasion through CXCL12/CXCR4 signaling
Goffart, Nicolas ULg; Kroonen, Jérome; Di Valentin, Emmanuel ULg et al

in Journal of Neuro-Oncology (2015), 17(1), 81-94

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See detailThe timing of surgery after neoadjuvant radiotherapy influences tumor dissemination in a preclinical model
Leroi, Natacha ULg; Sounni, Nor Eddine ULg; Van Overmeire, Eva et al

in Oncotarget (2015)

Neoadjuvant radiotherapy (neoRT) used in cancer treatments aims at improving local tumor control and patient overall survival. The neoRT schedule and the timing of the surgical treatment (ST) are ... [more ▼]

Neoadjuvant radiotherapy (neoRT) used in cancer treatments aims at improving local tumor control and patient overall survival. The neoRT schedule and the timing of the surgical treatment (ST) are empirically based and influenced by the clinician’s experience. The current study examines how the sequencing of neoRT and ST affects metastatic dissemination. In a breast carcinoma model, tumors were exposed to different neoRT schedules (2x5Gy or 5x2Gy) followed by surgery at day 4 or 11 post- RT. The impact on the tumor microenvironment and lung metastases was evaluated through immunohistochemical and flow cytometry analyses. After 2x5Gy, early ST (at day 4 post-RT) led to increased size and number of lung metastases as compared to ST performed at day 11. Inversely, after 5x2Gy neoRT, early ST protected the mice against lung metastases. This intriguing relationship between tumor aggressiveness and ST timing could not be explained by differences in classical parameters studied such as hypoxia, vessel density and matrix remodeling. The study of tumor-related inflammation and immunity reveals an increased circulating NK cell percentage following neoRT as compared to non irradiated mice. Then, radiation treatment and surgery were applied to tumor-bearing NOD/SCID mice. In the absence of NK cells, neoRT appears to increase lung metastatic dissemination as compared to non irradiated tumor-bearing mice. Altogether our data demonstrate that the neoRT schedule and the ST timing affect metastasis formation in a pre-clinical model and points out the potential role of NK cells. These findings highlight the importance to cautiously tailor the optimal window for ST following RT. [less ▲]

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See detailCOMMENT JE TRAITE ... Point de vue critique sur l'approche actuelle du cancer du pancreas localisé
VAN DAELE, Daniel ULg; Martinive, Philippe ULg; Loly, C. et al

in Revue medicale de Liege (2015), 70(11), 540-5

Surgical resection followed by chemotherapy is the actual standard of care for localized, deemed resectable, pancreatic ductal adenocarcinoma. Despite a better selection of surgical candidates and the ... [more ▼]

Surgical resection followed by chemotherapy is the actual standard of care for localized, deemed resectable, pancreatic ductal adenocarcinoma. Despite a better selection of surgical candidates and the actual performance of expert teams, the proportion of patients with a prolonged survival has not been ameliorated during the last three decades. The morphological determinants of resectability are the subject of limitations. In the future, only a better understanding of the biological process, an earlier diagnosis of purely localized disease and more efficient systemic therapies may lead to a better prognosis. Meanwhile, taking into account the prognostic factors associated with a lower chance of cure is currently a matter of debate. The optimal therapeutic sequence, being a surgery-first or a neoadjuvant approach is controversial. The theoretical advantages of preoperative chemotherapy eventually associated with chemo-radiation are demonstrated in other tumours and applicable to pancreatic cancer without any excess of operative mortality, early progression rates and, on the contrary with positive survival data. The completion rates of multi-modal therapy are in favour of the preoperative approach, which also gives the opportunity to select the best candidates for surgical resection. [less ▲]

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See detailEvolution dans la prise en charge de l'adenocarcinome du pancreas localise estime resecable.
VAN DAELE, Daniel ULg; Puleo, F.; Dumont, R. et al

in Revue medicale suisse (2015), 11(483), 1543-8

Pancreatic ductal adenocarcinoma is characterized by a high rate of early metastatic relapse. Surgical resection is still recognized as the cornerstone upfront therapy. However, reported 5 years survival ... [more ▼]

Pancreatic ductal adenocarcinoma is characterized by a high rate of early metastatic relapse. Surgical resection is still recognized as the cornerstone upfront therapy. However, reported 5 years survival rates are inferior to 20-25% even when surgery is followed by chemotherapy. Margins involvement on the surgical specimen (50 to 85%) and lymph node involvement (around 70%) both strongly impact survival. Median survivals are close to those of locally advanced diseases treated by chemotherapy or chemoradiotherapy, 15 to 16 months. This review focuses on adverse prognostic factors, post-operative outcomes and their impact on multimodality therapy completion rates and survivals in patients undergoing upfront surgery. Current data and emerging results from neoadjuvant series could lead to a change in the therapeutic strategy. [less ▲]

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See detailUtilisation de l'imagerie fonctionnelle en radiothérapie
LALLEMAND, François ULg; LAKOSI, Ferenc ULg; HUSTINX, Roland ULg et al

in Revue Médicale de Liège (2014), 69(Supp 1), 20-28

Les progrès technologiques réalisés par l’image- rie médicale l’ont placée au centre de la prise en charge des patients oncologiques, tant au niveau du diagnostic, du pro - nostic et du suivi que dans la ... [more ▼]

Les progrès technologiques réalisés par l’image- rie médicale l’ont placée au centre de la prise en charge des patients oncologiques, tant au niveau du diagnostic, du pro - nostic et du suivi que dans la prise en charge thérapeutique. En effet, l’imagerie représente, à l’heure actuelle, la pierre angulaire des traitements de radiothérapie. Les objectifs du radiothérapeute sont d’irradier le plus précisément possible la tumeur à dose curative, tout en évitant les organes sains. Pour y arriver, le radiothérapeute utilise de façon routinière l’imagerie anatomique (Scanner et IRM). Depuis quelques années, le développement des différentes imageries métabo - liques et fonctionnelles, comme l’imagerie par émission de positons (PET-CT) et la résonnance magnétique fonctionnelle, ouvrent de nouvelles possibilités thérapeutiques grâce aux informations qu’elles apportent sur la biologie des tumeurs. Cet article décrit, de manière non exhaustive, les différentes imageries anatomiques et métaboliques à la disposition du radiothérapeute. [less ▲]

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See detailFDG PET/CT for rectal carcinoma radiotherapy treatment planning : Comparison of functional volume delineation algorithms and clinical challenges.
WITHOFS, Nadia ULg; BERNARD, Claire ULg; VAN DER REST, Catherine ULg et al

in Journal of Applied Clinical Medical Physics (2014), 15(5), 216-228

PET/CT imaging could improve delineation of rectal carcinoma gross tumor volume (GTV) and reduce interobserver variability. The objective of this work was to compare various functional volume delineation ... [more ▼]

PET/CT imaging could improve delineation of rectal carcinoma gross tumor volume (GTV) and reduce interobserver variability. The objective of this work was to compare various functional volume delineation algorythms. [less ▲]

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See detailAdult mouse subventricular zones stimulate glioblastoma stem cells specific invasion through CXCL12/CXCR4 signaling.
Goffart, Nicolas; KROONEN, Jérôme ULg; Di Valentin, Emmanuel ULg et al

in Neuro-oncology (2014)

BACKGROUND: Patients with glioblastoma multiforme (GBM) have an overall median survival of 15 months. This catastrophic survival rate is the consequence of systematic relapses that could arise from ... [more ▼]

BACKGROUND: Patients with glioblastoma multiforme (GBM) have an overall median survival of 15 months. This catastrophic survival rate is the consequence of systematic relapses that could arise from remaining glioblastoma stem cells (GSCs) left behind after surgery. We previously demonstrated that GSCs are able to escape the tumor mass and specifically colonize the adult subventricular zones (SVZs) after transplantation. This specific localization, away from the initial injection site, therefore represents a high-quality model of a clinical obstacle to therapy and relapses because GSCs notably retain the ability to form secondary tumors. METHOD: In this work, we questioned the role of the CXCL12/CXCR4 signaling in the GSC-specific invasion of the SVZs. RESULTS: We demonstrated that both receptor and ligand are respectively expressed by different GBM cell populations and by the SVZ itself. In vitro migration bio-assays highlighted that human U87MG GSCs isolated from the SVZs (U87MG-SVZ) display stronger migratory abilities in response to recombinant CXCL12 and/or SVZ-conditioned medium (SVZ-CM) compared with cancer cells isolated from the tumor mass (U87MG-TM). Moreover, in vitro inhibition of the CXCR4 signaling significantly decreased the U87MG-SVZ cell migration in response to the SVZ-CM. Very interestingly, treating U87MG-xenografted mice with daily doses of AMD3100, a specific CXCR4 antagonist, prevented the specific invasion of the SVZ. Another in vivo experiment, using CXCR4-invalidated GBM cells, displayed similar results. CONCLUSION: Taken together, these data demonstrate the significant role of the CXCL12/CXCR4 signaling in this original model of brain cancer invasion. [less ▲]

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See detailLA RADIOTHÉRAPIE DANS LE CANCER DU RECTUM CHEZ LA PERSONNE ÂGÉE: Quel bénéfice pour le traitement ?
MARTINIVE, Philippe ULg; ALLEPAERTS, Sophie ULg; VAN DAELE, Daniel ULg et al

in Revue Médicale de Liège (2014), 69(Supp 1), 47-52

Dans les années à venir, nous serons de plus en plus amenés à prendre en charge des patients âgés en oncologie. Dans ce contexte, quelles sont les évidences scientifiques à notre disposition qui nous ... [more ▼]

Dans les années à venir, nous serons de plus en plus amenés à prendre en charge des patients âgés en oncologie. Dans ce contexte, quelles sont les évidences scientifiques à notre disposition qui nous permettent de prendre en charge de façon correcte cette population oncologique âgée ? Les patients âgés présentent souvent de multiples co-morbidités pouvant interférer avec le traitement oncologique rendant d’autant plus complexe leur prise en charge. Le pic d’inci - dence du cancer du rectum se situe autour des 80 ans, loin au-dessus de l’âge moyen des patients inclus dans les études cliniques. La survie globale des patients traités pour un cancer du rectum s’est améliorée au cours de la dernière décennie, essentiellement pour des patients de moins de 75 ans. Le trai - tement du cancer du rectum nécessite une approche multidis - ciplinaire. L’évaluation gériatrique en fait partie intégrante. Elle permet de définir au mieux la stratégie thérapeutique en fonction de l’état général du patient, de son contexte neuro- psychologique, fonctionnel et social. La radiothérapie joue un rôle majeur dans le traitement du rectum. Quelle est sa place chez les personnes âgées ? Bénéficient-elles également de la radiothérapie, comme la population jeune sélectionnée dans les études contrôlées ? Quel est l’impact de ce traitement sur la qualité de vie ? Voilà des questions essentielles auxquelles nous allons tenter d’apporter une réponse [less ▲]

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See detailLA RADIOTHÉRAPIE DANS LE CANCER DU RECTUM : quand, comment et pourquoi ?
MARTINIVE, Philippe ULg; VAN DAELE, Daniel ULg; LENNERTS, Evelyne ULg et al

in Revue Médicale de Liège (2014), 69(Supp 1), 37-46

Depuis plusieurs décades, la radiothérapie préopéra - toire ou postopératoire joue un rôle important dans le contrôle local de l’adénocarcinome du rectum. Cette dernière décennie, avec la systématisation ... [more ▼]

Depuis plusieurs décades, la radiothérapie préopéra - toire ou postopératoire joue un rôle important dans le contrôle local de l’adénocarcinome du rectum. Cette dernière décennie, avec la systématisation de la chirurgie d’exérèse en totalité du mésorectum (TME), le profil de récidive locale du cancer du rectum a été fortement modifié. Dans un tel contexte, la place de la radiothérapie doit être réévaluée en tenant compte de ces modifications. Dans cet article, nous proposons de faire la revue des différentes grandes études concernant les techniques et les indications d’un traitement de radiothérapie pré- ou post opératoire dans le contexte d’une chirurgie rectale TME. [less ▲]

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See detailLA RADIOBIOLOGIE POUR LES NÉOPHYTES
COUCKE, Philippe ULg; MARTINIVE, Philippe ULg

in Revue Médicale de Liège (2014), 69(Supp 1), 16-19

La radiothérapie moderne ne se base pas unique - ment sur l’exploitation des améliorations en informatique, imagerie et robotique. La meilleure distribution de la dose au niveau de la cible, avec ... [more ▼]

La radiothérapie moderne ne se base pas unique - ment sur l’exploitation des améliorations en informatique, imagerie et robotique. La meilleure distribution de la dose au niveau de la cible, avec l’épargne des tissus sains avoisinants, rend possible une nouvelle exploitation de concept de radio - biologie. L’exemple type est la redécouverte des traitements hypo-fractionnés. [less ▲]

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See detailOrthanc - Lightweight, Scriptable DICOM Server for Medical Image Management in Radiotherapy
JODOGNE, Sébastien ULg; SOBCZAK, Sonia ULg; DEVILLERS, Magali ULg et al

in Radiotherapy & Oncology (2013), 106(2), 488

High-quality radiotherapy (RT) treatment planning requires the combination of information arising from multiple medical imaging modalities. For this reason, RT implies the setup and the management of ... [more ▼]

High-quality radiotherapy (RT) treatment planning requires the combination of information arising from multiple medical imaging modalities. For this reason, RT implies the setup and the management of complex flows of images between the various modalities and software of the hospital. Even though biomedical images are most commonly stored and transferred using the DICOM standard, it remains hard to automatize and optimize these clinical flows that are very specific to each hospital. This stems from the fact that programming the DICOM network protocol requires both a high level of familiarity with the DICOM standard as well as substantial experience in computer programming. This motivates the introduction of the Orthanc software in the medical practice to improve the RT imaging workflow. [less ▲]

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