scholarly journals Development of Peritoneal Carcinomatosis in Epithelial Ovarian Cancer: A Review

2017 ◽  
Vol 66 (2) ◽  
pp. 67-83 ◽  
Author(s):  
Juliette O. A. M. van Baal ◽  
Cornelis J. F. van Noorden ◽  
Rienk Nieuwland ◽  
Koen K. Van de Vijver ◽  
Auguste Sturk ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Epithelial Ovarian Cancer ◽  
Peritoneal Carcinomatosis ◽  
Current Knowledge ◽  
Future Research ◽  
Depth Of Invasion ◽  
Peritoneal Cells ◽  
Ligand Interactions ◽  
Underlying Mechanisms ◽  
Tumor Adhesion

Epithelial ovarian cancer (EOC) metastasizes intra-abdominally with often numerous, superficial, small-sized lesions. This so-called peritoneal carcinomatosis is difficult to treat, and peritoneal recurrences are frequently observed, leading to a poor prognosis. Underlying mechanisms of interactions between EOC and peritoneal cells are incompletely understood. This review summarizes and discusses the development of peritoneal carcinomatosis from a cell-biological perspective, focusing on characteristics of EOC and peritoneal cells. We aim to provide insight into how peritoneum facilitates tumor adhesion but limits size of lesions and depth of invasion. The development of peritoneal carcinomatosis is a multistep process that requires adaptations of EOC and peritoneal cells. Mechanisms that enable tumor adhesion and growth involve cadherin restructuring on EOC cells, integrin-mediated adhesion, and mesothelial evasion by mechanical forces driven by integrin-ligand interactions. Clinical trials targeting these mechanisms, however, showed only limited effects. Other factors that inhibit tumor growth and deep invasion are virtually unknown. Future studies are needed to elucidate the exact mechanisms that underlie the development and limited growth of peritoneal carcinomatosis. This review on development of peritoneal carcinomatosis of EOC summarizes the current knowledge and its limitations. Clarification of the stepwise process may inspire future research to investigate new treatment approaches of peritoneal carcinomatosis.

scholarly journals CSF1R-related leukoencephalopathy

Neurology ◽  
2018 ◽  
Vol 91 (24) ◽  
pp. 1092-1104 ◽  
Author(s):  
Takuya Konno ◽  
Koji Kasanuki ◽  
Takeshi Ikeuchi ◽  
Dennis W. Dickson ◽  
Zbigniew K. Wszolek
Keyword(s):  
White Matter ◽  
Cultured Cells ◽  
Clinical Symptoms ◽  
Current Knowledge ◽  
Gene Mutations ◽  
Future Research ◽  
Primary Role ◽  
Extrapyramidal Signs ◽  
Underlying Mechanisms

Since the discovery of CSF1R gene mutations in families with hereditary diffuse leukoencephalopathy with spheroids in 2012, more than 70 different mutations have been identified around the world. Through the analyses of mutation carriers, CSF1R-related leukoencephalopathy has been distinctly characterized clinically, radiologically, and pathologically. Typically, patients present with frontotemporal dementia-like phenotype in their 40s–50s, accompanied by motor symptoms, including pyramidal and extrapyramidal signs. Women tend to develop the clinical symptoms at a younger age than men. On brain imaging, in addition to white matter abnormalities, thinning of the corpus callosum, diffusion-restricted lesions in the white matter, and brain calcifications are hallmarks. Primary axonopathy followed by demyelination was suggested by pathology. Haploinsufficiency of colony-stimulating factor-1 receptor (CSF1R) is evident in a patient with a frameshift mutation, facilitating the establishment of Csf1r haploinsufficient mouse model. These mice develop clinical, radiologic, and pathologic phenotypes consistent with those of human patients with CSF1R mutations. In vitro, perturbation of CSF1R signaling is shown in cultured cells expressing mutant CSF1R. However, the underlying mechanisms by which CSF1R mutations selectively lead to white matter degeneration remains to be elucidated. Given that CSF1R mainly expresses in microglia, CSF1R-related leukoencephalopathy is representative of primary microgliopathies, of which microglia have a pivotal and primary role in pathogenesis. In this review, we address the current knowledge of CSF1R-related leukoencephalopathy and discuss the putative pathophysiology, with a focus on microglia, as well as future research directions.

scholarly journals Fischer 344 Rat: A Preclinical Model for Epithelial Ovarian Cancer Folate-Targeted Therapy

2015 ◽  
Vol 25 (7) ◽  
pp. 1194-1200 ◽  
Author(s):  
Henri Azaïs ◽  
Gurvan Queniat ◽  
Caroline Bonner ◽  
Olivier Kerdraon ◽  
Meryem Tardivel ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Epithelial Ovarian Cancer ◽  
Peritoneal Carcinomatosis ◽  
Cancer Cell ◽  
Targeted Therapies ◽  
Ovarian Cancer Cell ◽  
Preclinical Model ◽  
Fischer 344 ◽  
Fischer 344 Rat

ObjectiveOvarian cancer prognosis remains dire after primary therapy. Recurrence rates are disappointingly high as 60% of women with advanced epithelial ovarian cancer considered in remission will develop recurrent disease within 5 years. Special attention to undetected peritoneal metastasis and residual tumorous cells during surgery is necessary as they are the main predictive factors of recurrences. Folate receptor α (FRα) shows promising prospects in targeting ovarian cancerous cells. Our aim was to determine if the Fischer model described by Rose et al could be used to evaluate folate-targeted therapies in preclinical studies.MethodsNuTu-19 epithelial ovarian cancer cell line was used to induce peritoneal carcinomatosis in female Fischer 344 rats. FRα expression by NuTu-19 cells was assessed in vitro by immunofluorescence using “Cytospin®” protocol. In vitro folate-targeted compound uptake by NuTu-19 cells was evaluated by incubation of FRα-positive ovarian cancer cell lines (NuTu-19/SKOV-3/OVCAR-3/IGROV-1) with or without (control) a folate-targeted photosensitizer. Intracellular incorporation was assessed by confocal microscopy. Determination of in vivo FRα tissue expression by several organs of the peritoneal cavity was studied by immunohistochemistry.ResultsNuTu-19 cells express FRα which allows intracellular incorporation of folate-targeted compound by endocytosis. FRα is expressed in tumor tissue, ovary, and liver. Peritoneum, colon, small intestine, and kidney do not express the receptor.ConclusionsFemale Fischer 344 rat is an inexpensive reproducible and efficient preclinical model to study ovarian peritoneal carcinomatosis folate-targeted therapies.

scholarly journals The Role of Intra-Tumoral Heterogeneity and Its Clinical Relevance in Epithelial Ovarian Cancer Recurrence and Metastasis

Cancers ◽  
2019 ◽  
Vol 11 (8) ◽  
pp. 1083 ◽  
Author(s):  
Roberts ◽  
Cardenas ◽  
Tedja
Keyword(s):  
Ovarian Cancer ◽  
Epithelial Ovarian Cancer ◽  
Tumor Heterogeneity ◽  
Clonal Evolution ◽  
Gynecologic Cancer ◽  
Cancer Recurrence ◽  
Cell Types ◽  
Future Research ◽  
Major Barrier ◽  
The Impact

Epithelial ovarian cancer is the deadliest gynecologic cancer, due in large part to recurrent tumors. Recurrences tend to have metastasized, mainly in the peritoneal cavity and developed resistance to the first line chemotherapy. Key to the progression and ultimate lethality of ovarian cancer is the existence of extensive intra-tumoral heterogeneity (ITH). In this review, we describe the genetic and epigenetic changes that have been reported to give rise to different cell populations in ovarian cancer. We also describe at length the contributions made to heterogeneity by both linear and parallel models of clonal evolution and the existence of cancer stem cells. We dissect the key biological signals from the tumor microenvironment, both directly from other cell types in the vicinity and soluble or circulating factors. Finally, we discuss the impact of tumor heterogeneity on the choice of therapeutic approaches in the clinic. Variability in ovarian tumors remains a major barrier to effective therapy, but by leveraging future research into tumor heterogeneity, we may be able to overcome this barrier and provide more effective, personalized therapy to patients.

scholarly journals Epithelial Ovarian Cancer and the Immune System: Biology, Interactions, Challenges and Potential Advances for Immunotherapy

2020 ◽  
Vol 9 (9) ◽  
pp. 2967
Author(s):  
Anne M. Macpherson ◽  
Simon C. Barry ◽  
Carmela Ricciardelli ◽  
Martin K. Oehler
Keyword(s):  
Ovarian Cancer ◽  
Immune System ◽  
Epithelial Ovarian Cancer ◽  
Current Knowledge ◽  
Tumour Microenvironment ◽  
Tumour Immunology ◽  
The Us ◽  
Cancer Types ◽  
Cancer Immunotherapeutic ◽  
Cancer Immunotherapies

Recent advances in the understanding of immune function and the interactions with tumour cells have led to the development of various cancer immunotherapies and strategies for specific cancer types. However, despite some stunning successes with some malignancies such as melanomas and lung cancer, most patients receive little or no benefit from immunotherapy, which has been attributed to the tumour microenvironment and immune evasion. Although the US Food and Drug Administration have approved immunotherapies for some cancers, to date, only the anti-angiogenic antibody bevacizumab is approved for the treatment of epithelial ovarian cancer. Immunotherapeutic strategies for ovarian cancer are still under development and being tested in numerous clinical trials. A detailed understanding of the interactions between cancer and the immune system is vital for optimisation of immunotherapies either alone or when combined with chemotherapy and other therapies. This article, in two main parts, provides an overview of: (1) components of the normal immune system and current knowledge regarding tumour immunology, biology and their interactions; (2) strategies, and targets, together with challenges and potential innovative approaches for cancer immunotherapy, with attention given to epithelial ovarian cancer.

Malignant Bowel Obstruction in Relapsed Ovarian Cancer With Peritoneal Carcinomatosis: An Occlusive State

2017 ◽  
Vol 27 (7) ◽  
pp. 1367-1372 ◽  
Author(s):  
Pedro Martinez Castro ◽  
Lara Vargas ◽  
Antonio Mancheño ◽  
Salvador Martín Utrilla ◽  
Francisco Pascual ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Epithelial Ovarian Cancer ◽  
Peritoneal Carcinomatosis ◽  
Bowel Obstruction ◽  
First Episode ◽  
Time Interval ◽  
Short Time Interval ◽  
Low Grade ◽  
Malignant Bowel Obstruction ◽  
Short Time

ObjectiveThe aim of this study was to describe the clinical and oncological outcomes of women with malignant bowel obstruction (MBO) for relapsed ovarian cancer and peritoneal carcinomatosis.MethodsA retrospective cohort study was performed in all consecutive patients admitted at Instituto Valenciano de Oncología, Valencia, Spain, between July 2013 and July 2016 with MBO for relapsed ovarian cancer and peritoneal carcinomatosis. All patients underwent the same protocol of conservative management. Surgical treatment was indicated only in selected cases.ResultsThere were a total of 22 patients presenting 59 episodes of MBO; 17 (77.2%) of those patients presented more than 1 episode of MBO. All patients had serous epithelial ovarian cancer; 18 (81.8%) were high grade, and 4 (18.2%) low-grade tumors. The median (range) number of episodes per patient was 3 (range, 1–7) with a mean length of hospitalization of 13 (SD, 13.6) days. The median time interval between episodes of MBO (54 episodes in 17 patients) was 17 days (range, 1–727 days). Twenty of 22 patients died with a median overall survival time from the first episode of MBO of 95 days (95% confidence interval, 49–124 days).ConclusionsPatients with MBO due to relapsed epithelial ovarian cancer in the peritoneal carcinomatosis setting have a short life expectancy, presenting a median of 3 episodes of MBO until death, with a short time interval between episodes. These findings show that bowel obstruction can represent a constant status over time until death.

Sign in / Sign up

Export Citation Format

Share Document