المؤلفون: Matti Ullah, Shahsoltan Mirshahi, Azadeh Valinattaj Omran, Iman Aldybiat, Sullyvan Crepaux, Jeannette Soria, Geneviève Contant, Marc Pocard, Massoud Mirshahi

المصدر: Cancers, Vol 16, Iss 5, p 928 (2024)

مصطلحات موضوعية: blood viscoelasticity, plasma histones, cancer rheology, clot degradation, cancer thrombosis, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282

الوصف: Background: Blood viscoelasticity and plasma protein levels can play an important role in the diagnosis and prognosis of cancer. However, the role of histones and DNA in modulating blood clot properties remains to be investigated. This study investigates the differences in blood viscoelasticity and plasma protein levels among cancer patients, individuals with other diseases, and healthy individuals. Methods: Blood samples were collected from 101 participants, including 45 cancer patients, 22 healthy individuals, and 34 individuals with other diseases. Rheological properties of clots formed in vitro by reconstituted elements of fibrinogen or plasma were analyzed with an Anton Paar Rheometer, USA. Plasma protein levels of D-dimer, TPA, EPCR, fibrinogen, and histone H3 were measured through ELISA. Blood clots were formed with or without DNA and histones (H3) by adding thrombin and calcium to plasma samples, and were evaluated for viscoelasticity, permeability, and degradation. Results: Cancer patients show higher blood viscoelasticity and plasma D-dimer levels compared to healthy individuals and individuals with other diseases. Our in vitro analysis showed that the addition of histone to the plasma results in a significant decrease in viscoelasticity and mean fiber thickness of the clot formed thereafter. In parallel studies, using plasma from patients, DNA and histones were detected in fibrin clots and were associated with less degradation by t-PA. Moreover, our results show that the presence of DNA and histones not only increases clots’ permeability, but also makes them more prone to degradation. Conclusions: Plasma histones and DNA affect the structure of the clot formed and induce defective fibrinolysis. Moreover, the increased viscoelastic properties of plasma from cancer patients can be used as potential biomarkers in cancer prognosis.

وصف الملف: electronic resource

العلاقة: https://www.mdpi.com/2072-6694/16/5/928Test; https://doaj.org/toc/2072-6694Test

الوصول الحر: https://doaj.org/article/e865ce13c7464b09a10b162f226caf4dTest

المؤلفون: Anne-Cécile Ezanno, Brice Malgras, Pierre-Louis Conan, Adeline Aime, Jade Fawaz, Hugo Picchi, Solène Doat, Marc Pocard

المصدر: PLoS ONE, Vol 18, Iss 11 (2023)

مصطلحات موضوعية: Medicine, Science

وصف الملف: electronic resource

العلاقة: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10688840/?tool=EBITest; https://doaj.org/toc/1932-6203Test

الوصول الحر: https://doaj.org/article/c31f69ff83b64738af23fe06c6aa5465Test

المؤلفون: Maurizio Cardi, Marc Pocard, Rea Lo Dico, Gianmaria Fiorentini, Mario Valle, Roberta Gelmini, Marco Vaira, Enrico Maria Pasqual, Salvatore Asero, Gianluca Baiocchi, Andrea Di Giorgio, Alessandra Spagnoli, Francesco Di Marzo, Bianca Sollazzo, Giuseppe D’Ermo, Daniele Biacchi, Franco Iafrate, Paolo Sammartino

المصدر: Frontiers in Oncology, Vol 12 (2022)

مصطلحات موضوعية: breast cancer, peritoneal metastases, cytoreductive surgery, oligometastatic disease, ascites treatment, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282

الوصف: BackgroundEven though breast cancer is the most frequent extra-abdominal tumor causing peritoneal metastases, clear clinical guidelines are lacking. Our aim is to establish whether cytoreductive surgery (CRS) could be considered in selected patients with peritoneal metastases from breast cancer (PMBC) to manage abdominal spread and allow patients to resume or complete other medical treatments.MethodsWe considered patients with PMBC treated in 10 referral centers from January 2002 to May 2019. Clinical data included primary cancer characteristics (age, histology, and TNM) and data on metastatic disease (interval between primary BC and PM, molecular subtype, other metastases, and peritoneal spread). Overall survival (OS) was estimated using the Kaplan–Meier method. Univariate and multivariable data for OS were analyzed using the Cox proportional hazards model.ResultsOf the 49 women with PMBC, 20 were treated with curative aim (CRS with or without HIPEC) and 29 were treated with non-curative procedures. The 10-year OS rate was 27%. Patients treated with curative intent had a better OS than patients treated with non-curative procedures (89.2% vs. 6% at 36 months, p < 0.001). Risk factors significantly influencing survival were age at primary BC, interval between BC and PM diagnosis, extra-peritoneal metastases, and molecular subtype.ConclusionsThe improved outcome in selected cases after a multidisciplinary approach including surgery should lead researchers to regard PMBC patients with greater attention despite their scarce epidemiological impact. Our collective efforts give new information, suggest room for improvement, and point to further research for a hitherto poorly studied aspect of metastatic BC.

وصف الملف: electronic resource

العلاقة: https://www.frontiersin.org/articles/10.3389/fonc.2022.822550/fullTest; https://doaj.org/toc/2234-943XTest

الوصول الحر: https://doaj.org/article/aef7c4d897844c76b4f22591f7cd1817Test

المؤلفون: Vahan Kepenekian, Julien Péron, Diane Goéré, Olivia Sgarbura, Jean-Baptiste Delhorme, Clarisse Eveno, Nazim Benzerdjeb, Isabelle Bonnefoy, Laurent Villeneuve, Pascal Rousset, Karine Abboud, Marc Pocard, Olivier Glehen, On Behalf RENAPE (French Network for Rare Peritoneal Malignancies)

المصدر: International Journal of Hyperthermia, Vol 38, Iss 1, Pp 805-814 (2021)

مصطلحات موضوعية: multicystic mesothelioma, cytoreductive surgery, crs, hyperthermic intraperitoneal chemotherapy, hipec, fertility, Medical technology, R855-855.5

الوصف: Background Multicystic peritoneal mesothelioma (MCPM) is a rare, slowly growing, condition prone to recur after surgery. The role of hyperthermic intraperitoneal chemotherapy (HIPEC) added to complete cytoreductive surgery (CRS) remains controversial and difficult to assess. As patients are mostly reproductive age women, surgical approach, and fertility considerations are important aspects of the management. This observational retrospective review aimed to accurate treatment strategy reflections. Methods The RENAPE database (French expert centers network) was analyzed over a 1999–2019 period. MCPM patients treated with CRS were included. A special focus on HIPEC, mini-invasive approach, and fertility considerations was performed. Results Overall 60 patients (50 women) were included with a median PCI of 10 (4–14) allowing 97% of complete surgery, followed by HIPEC in 82% of patients. A quarter of patients had a laparoscopic approach. Twelve patients (20%) recurred with a 3-year recurrence free survival of 84.2% (95% confidence interval 74.7–95.0). The hazard of recurrence was numerically reduced among patients receiving HIPEC, however, not statistically significant (hazard ratio 0.41, 0.12–1.42, p = 0.200). A severe post-operative adverse event occurred in 22% of patients with five patients submitted to a subsequent reoperation. Among four patients with a childbearing desire, three were successful (two had a laparoscopic-CRS-HIPEC and one a conventional CRS without HIPEC). Conclusion MCPM patients treatment should aim at a complete CRS. The intraoperative treatment options as laparoscopic approach, fertility function sparing and HIPEC should be discussed in expert centers to propose the most appropriate strategy.

وصف الملف: electronic resource

العلاقة: https://doaj.org/toc/0265-6736Test; https://doaj.org/toc/1464-5157Test

الوصول الحر: https://doaj.org/article/16c3835bece54622aad1ee8e54ab036aTest

المؤلفون: Iman Al dybiat, Shahsoltan Mirshahi, Meriem Belalou, Djedjiga Abdelhamid, Shahid Shah, Matti Ullah, Jeannette Soria, Marc Pocard, Massoud Mirshahi

المصدر: Neoplasia: An International Journal for Oncology Research, Vol 22, Iss 12, Pp 809-819 (2020)

مصطلحات موضوعية: Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282

الوصف: Aim: Evaluation of fibrin role on cancer cells implantation in injured tissues and studying the molecular mechanism of cancer cell interaction with the peritoneal damage. Material and methods: Mouse colon cancer (CT26) and human mesothelial cells (HMCs) were used. CT26 cells were implanted on injured peritoneal zones. Icodextrin was used as a lubricant. For in vitro studies, fibrin clots from human plasma were used. The cell-fibrin interaction was observed by optical, electronic, and confocal microscopies. Aprotinin was used as a plasmin inhibitor. Hemostasis impact quantified by (1) the fibrin degradation product D-Dimer and PAR expression in HMCs; (2) the expression of plasminogen activator (PA) and its inhibitor (PAI-1) in cancer cells by qPCR and in supernatants through ELISA after in vitro HMC incubation with 2U of thrombin for 24 h. Results: (i) Cancer cell lines were adhered and implanted into the wound area in vivo in both the incision and peeling zones of the peritoneum and on the fibrin network in vitro. (ii) Icodextrin significantly inhibited cancer nodule formation in the scar and the incision or peritoneal damaged zones after surgery. (iii) In in vitro studies, cancer cell interaction with the fibrin clot generated a lysed area, causing an increase in plasmin-dependent fibrinolysis measured by D-dimer levels in the supernatants that was inhibited by aprotinin. (iv) Aprotinin inhibited cell-fibrin interaction and invasion. (v) Thrombin upregulates PAI-1 and downregulates PA expression in HMC. Conclusion: Injured tissues favor cancer cell implantation through generated fibrin. Fibrin-cancer cells adhesion can be inhibited by icodextrin.

وصف الملف: electronic resource

العلاقة: http://www.sciencedirect.com/science/article/pii/S1476558620301524Test; https://doaj.org/toc/1476-5586Test

الوصول الحر: https://doaj.org/article/acf4e9e91eea40609d2b55ff17a5eea6Test

المؤلفون: Iman Al Dybiat, Alibi Baitukha, Cynthia Pimpie, Rachid Kaci, Marc Pocard, Farzaneh Arefi Khonsari, Massoud Mirshahi

المصدر: BMC Cancer, Vol 20, Iss 1, Pp 1-11 (2020)

مصطلحات موضوعية: Cancer, Drug delivery, Film implantation, Multi-nanolayer technology, Radio frequency plasma, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282

الوصف: Abstract Background It may be impossible to perform cancer surgery with free margins in the presence of an unresectable structure. Local drug treatment after surgery has been proposed to increase the rate of tumor control. Methods Multi-nanolayers (10-330 nm) were generated by a low-pressure (375mTorr) inductively coupled plasma (13.56 MHz) reactor for anticancer drug delivery by the deposition of polycaprolactone-polyethylene glycol multistack barrier on the collagen membrane (100 μm thickness). Carboplatin (300 μg/cm2) was used for the in vitro and in vivo investigations. Energy-dispersive X-ray spectroscopy (15 keV), scanning electron microscopy and inductively coupled plasma mass spectrometry were used to detect the presence of carboplatin in the nanolayer, the tumor sample and the culture medium. Preclinical studies were performed on ovarian (OVCAR-3NIH) and colon (CT26) cancer cell lines as xenografts (45 days) and allografts (23 days) in Swiss-nude (n = 6) and immunocompetent BALB/cByJ mice (n = 24), respectively. Results The loading of carboplatin or other drugs between the nanofilm on the collagen membrane did not modify the mesh complex architecture or the drug properties. Drugs were detectable on the membrane for more than 2 weeks in the in vitro analysis and more than 10 days in the in vivo analysis. Cytotoxic mesh decreased cell adherence (down 5.42-fold) and induced cancer cell destruction (up to 7.87-fold). Implantation of the mesh on the mouse tumor nodule modified the cell architecture and decreased the tumor size (50.26%) compared to the control by inducing cell apoptosis. Conclusion Plasma technology allows a mesh to be built with multi-nanolayer anticancer drug delivery on collagen membranes.

وصف الملف: electronic resource

العلاقة: http://link.springer.com/article/10.1186/s12885-020-06989-wTest; https://doaj.org/toc/1471-2407Test

الوصول الحر: https://doaj.org/article/4a97dc7d6fa4428bbc0b0c2aa6217780Test

المؤلفون: Matthias Barral, Imane El-Sanharawi, Anthony Dohan, Maxime Sebuhyan, Alexis Guedon, Audrey Delarue, Alexandre Boutigny, Nassim Mohamedi, Benjamin Magnan, Salim Kemel, Chahinez Ketfi, Nathalie Kubis, Annouk Bisdorff-Bresson, Marc Pocard, Philippe Bonnin

المصدر: Frontiers in Physiology, Vol 12 (2021)

مصطلحات موضوعية: wall shear stress, blood flow velocity, superior mesenteric artery, peritoneal carcinomatosis, pseudomyxoma peritonei, carotid artery, Physiology, QP1-981

الوصف: In the presence of tumor angiogenesis, blood flow must increase, leading to an elevation of blood flow velocities (BFVels) and wall shear stress (WSS) in upstream native arteries. An adaptive arterial remodeling is stimulated, whose purpose lies in the enlargement of the arterial inner diameter, aiming for normalization of BFVels and WSS. Remodeling engages delayed processes that are efficient only several weeks/months after initiation, independent from those governing expansion of the neovascular network. Therefore, during tumor expansion, there is a time interval during which elevation of BFVels and WSS could reflect disease progression. Conversely, during the period of stability, BFVels and WSS drop back to normal values due to the achievement of remodeling processes. Ovarian peritoneal carcinomatosis (OPC), pseudomyxoma peritonei (PMP), and superficial arteriovenous malformations (AVMs) are diseases characterized by the development of abnormal vascular networks developed on native ones. In OPC and PMP, preoperative blood flow in the superior mesenteric artery (SMA) correlated with the per-operative peritoneal carcinomatosis index (OPC: n = 21, R = 0.79, p < 0.0001, PMP: n = 66, R = 0.63, p < 0.0001). Moreover, 1 year after surgery, WSS in the SMA helped in distinguishing patients with PMP from those without disease progression [ROC-curve analysis, AUC = 0.978 (0.902–0.999), p < 0.0001, sensitivity: 100.0%, specificity: 93.5%, cutoff: 12.1 dynes/cm2]. Similarly, WSS in the ipsilateral afferent arteries close to the lesion distinguished stable from progressive AVM [ROC-curve analysis, AUC: 0.988, (0.919–1.000), p < 0.0001, sensitivity: 93.5%, specificity: 95.7%; cutoff: 26.5 dynes/cm2]. Blood flow volume is indicative of the tumor burden in OPC and PMP, and WSS represents an early sensitive and specific vascular marker of disease progression in PMP and AVM.

وصف الملف: electronic resource

العلاقة: https://www.frontiersin.org/articles/10.3389/fphys.2021.693052/fullTest; https://doaj.org/toc/1664-042XTest

الوصول الحر: https://doaj.org/article/034e923c80d8439c85b3c5cc416abbe8Test

المؤلفون: Hayet Bouzid, Feryel Soualmia, Katerina Oikonomopoulou, Antoninus Soosaipillai, Francine Walker, Khaoula Louati, Rea Lo Dico, Marc Pocard, Chahrazade El Amri, Natalia A. Ignatenko, Dalila Darmoul

المصدر: Biomolecules, Vol 12, Iss 7, p 1003 (2022)

مصطلحات موضوعية: kallikrein-related peptidase 6, protease-activated receptors, colorectal cancer, metastasis, signaling, extracellular matrix, Microbiology, QR1-502

الوصف: Kallikrein-related peptidases (KLKs) are implicated in many cancer-related processes. KLK6, one of the 15 KLK family members, is a promising biomarker for diagnosis of many cancers and has been associated with poor prognosis of colorectal cancer (CRC) patients. Herein, we evaluated the expression and cellular functions of KLK6 in colon cancer-derived cell lines and in clinical samples from CRC patients. We showed that, although many KLKs transcripts are upregulated in colon cancer-derived cell lines, KLK6, KLK10, and KLK11 are the most highly secreted proteins. KLK6 induced calcium flux in HT29 cells by activation and internalization of protease-activated receptor 2 (PAR2). Furthermore, KLK6 induced extracellular signal–regulated kinases 1 and 2 (ERK1/2) phosphorylation. KLK6 suppression in HCT-116 colon cancer cells decreased the colony formation, increased cell adhesion to extracellular matrix proteins, and reduced spheroid formation and compaction. Immunohistochemistry (IHC) analysis demonstrated ectopic expression of KLK6 in human colon adenocarcinomas but not in normal epithelia. Importantly, high levels of KLK6 protein were detected in the ascites of CRC patients with peritoneal metastasis, but not in benign ascites. These data indicate that KLK6 overexpression is associated with aggressive CRC, and may be applied to differentiate between benign and malignant ascites.

وصف الملف: electronic resource

العلاقة: https://www.mdpi.com/2218-273X/12/7/1003Test; https://doaj.org/toc/2218-273XTest

الوصول الحر: https://doaj.org/article/022da2a0d5b54c6ab2da745c01190ed5Test

المؤلفون: Matti Ullah, Dallel Azazzen, Rachid Kaci, Nadia Benabbou, Eric Pujade Lauraine, Marc Pocard, Massoud Mirshahi

المصدر: Neoplasia: An International Journal for Oncology Research, Vol 21, Iss 3, Pp 331-342 (2019)

مصطلحات موضوعية: Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282

الوصف: The present study focuses on the influence of the tumor microenvironment on the expression of HLA-G in ovarian cancer and its impact on immune cells. We used carcinomatosis fluids (n = 16) collected from patients diagnosed with epithelial ovarian cancer, detected by an increase in CA125 levels. Our results indicate that HLA-G is expressed by 1) ascitic cell clusters, 2) stromal cells (hospicells) extracted from cancer cell clusters, and 3) cancer cell lines and tumor cells. The origin of HLA-G was linked to inflammatory cytokines present in the cancer microenvironment. In parallel, the ascitic fluid of patients with ovarian cancer contains soluble HLA-G (sHLA-G). The mesothelial cell layer and submesothelial tissues, as well as the immune cell infiltrate, do not secrete HLA-G. In contrast, sHLA-G is absorbed by peritoneal tissues along with mesothelial layers as well as immune cell infiltrates. We demonstrated that interleukin-1β along with TGF-β can be a major HLA-G–inducing factor that upregulates HLA-G expression through the NF-κB pathway. The level of HLA-G in ascites correlated positively with the expression of T regulatory (T-regs) cells, while it negatively correlated with the expression of natural killer and memory cells in tumor-infiltrating immune cells. In conclusion, the production of HLA-G is associated with the presence of inflammatory cytokines and is strongly correlated with microenvironment tolerant cells such as T-regs and diminution of NK and memory T cells.

وصف الملف: electronic resource

العلاقة: http://www.sciencedirect.com/science/article/pii/S1476558618306043Test; https://doaj.org/toc/1476-5586Test

الوصول الحر: https://doaj.org/article/17670eb378f14ebb9c2d9df1df944c26Test

المؤلفون: Gaëtan Mary, Brice Malgras, Jose Efrain Perez, Irène Nagle, Nathalie Luciani, Cynthia Pimpie, Atef Asnacios, Marc Pocard, Myriam Reffay, Claire Wilhelm

المصدر: Cancers, Vol 14, Iss 2, p 366 (2022)

مصطلحات موضوعية: cancer spheroids, forces and cancer, magnetic nanoparticles, magnetic force, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282

الوصف: A growing tumor is submitted to ever-evolving mechanical stress. Endoscopic procedures add additional constraints. However, the impact of mechanical forces on cancer progression is still debated. Herein, a set of magnetic methods is proposed to form tumor spheroids and to subject them to remote deformation, mimicking stent-imposed compression. Upon application of a permanent magnet, the magnetic tumor spheroids (formed from colon cancer cells or from glioblastoma cells) are compressed by 50% of their initial diameters. Such significant deformation triggers an increase in the spheroid proliferation for both cell lines, correlated with an increase in the number of proliferating cells toward its center and associated with an overexpression of the matrix metalloproteinase−9 (MMP−9). In vivo peritoneal injection of the spheroids made from colon cancer cells confirmed the increased aggressiveness of the compressed spheroids, with almost a doubling of the peritoneal cancer index (PCI), as compared with non-stimulated spheroids. Moreover, liver metastasis of labeled cells was observed only in animals grafted with stimulated spheroids. Altogether, these results demonstrate that a large compression of tumor spheroids enhances cancer proliferation and metastatic process and could have implications in clinical procedures where tumor compression plays a role.

وصف الملف: electronic resource

العلاقة: https://www.mdpi.com/2072-6694/14/2/366Test; https://doaj.org/toc/2072-6694Test

الوصول الحر: https://doaj.org/article/69c7d05123a64e2f94dbfb13e21bb9fcTest