Download or read book The Tumor Microenvironment of High Grade Serous Ovarian Cancer written by M. Sharon Stack and published by MDPI. This book was released on 2019-02-06 with total page 435 pages. Available in PDF, EPUB and Kindle. Book excerpt: This book is a printed edition of the Special Issue "The Tumor Microenvironment of High Grade Serous Ovarian Cancer" that was published in Cancers

Download or read book The Tumor Microenvironment of High Grade Serous Ovarian Cancer written by Kenneth P. Nephew and published by . This book was released on 2019 with total page 1 pages. Available in PDF, EPUB and Kindle. Book excerpt: The Special Issue on high grade serous ovarian cancer (HGSOC) and the contribution of the tumor microenviroment (TME) consists of reviews contributed by leaders in the OC field. As HGSOC metastases have a highly complex TME, there is an urgent need to better understand the TME in general, its distinct components in particular, and the role of the TME in the context of disease recurrence and development of chemoresistance. The Special Issue incorporates the current understanding of the different parts of thd TME components, including the cancer cells themselves, the cells surrounding the cancer cells or stromal cells, and the cells of the immune system, which are attracted to the site of metastases. In addition to these cells of the TME, the role of various cellular factors made by the cells of the TME are also the subject of the reviews. In addition, reviews in this Special Issue cover the complex relationships between the molecular mechanisms of HGSOC progression, including genomic, epigenomic and transcriptomic changes and changes in the immune cell landscape, as these may provide attractive new molecular targets for HGSOC therapy.

Download or read book Characterization of the Tumour Microenvironment in High grade Serous Ovarian Cancer HGSOC Prognostic Value of the Lymphocytic Infiltration Patterns and Immune related Genes written by Juan Gilabert-Estellu00e9s and published by . This book was released on 2017 with total page pages. Available in PDF, EPUB and Kindle. Book excerpt: Background: Lymphocytic infiltration areas (immunoreactive), frequently found in high-grade serous ovarian cancer (HGSOC), are associated with a better prognosis and increased survival. The cross-talk between tumour cells and lymphocytes conditions the capacity of the immune system (IS) to cope with the tumour in the so-called immune-checkpoints. Therefore, assessing IS-related genes and infiltration patters might provide valuable prognostic biomarkers. Methodology: This retrospective study includes 57 samples from patients with HGSOC who underwent cytoreductive surgery at Hospital General (Valencia). Clinical variables, the features of the lymphocytic infiltration (pattern, localization and degree) and the expression of immune-related genes (CD4, CD8, FOXP3, ICOSL, ICOS, PD-L2, TGFu03b21, CD25, IDO1, IL7R, PD-L1, CTL4, CXCR4, PD1, OX40, LGAL and CD137) were evaluated to assess prognosis. Results: The median age was 61.5 years, being the majority of patients in advanced FIGO stages (76.3% III-IV vs. 23.7%, I-II stages). Patients with u226565 years and III-IV stages showed a shorter overall survival (OS, 30.17 vs. 99.90 months, p=0.009; 38.73 months vs. NR, p=0.005, respectively). Regarding immunoreactive areas, patients with an intratumoural pattern of lymphocyte infiltration had better prognosis compared to those that only had a peritumoural pattern (OS: 44.57 months vs. NR, p=0.041). In addition, those with a diffuse infiltration pattern presented a better prognosis compared to those with a focal pattern (OS, 20.20 months vs. NR p=0.003). Regarding gene expression, 11 genes (CTLA4, FOXP3, CD25, CSCR4, IDO1, PD-1, PD-L1, PD-L2, OX40L, ICOS, ICOSL, LGAL9 and CD137 were found over-expressed, but only CD137 displayed a significant prognostic value (OS: 50 months vs NR, p=0.020). Conclusion: HGSOC represents a group of highly immunoreactive tumours. Best prognosis is represented by patients with an intratumoural and diffuse pattern of lymphocytic infiltration and lower CD137 expression, which may be considered as valuable prognostic markers. These interesting findings could open a new window for immunotherapeutic approaches in HGSOC.

Download or read book Ovarian Cancers written by National Academies of Sciences, Engineering, and Medicine and published by National Academies Press. This book was released on 2016-04-25 with total page 397 pages. Available in PDF, EPUB and Kindle. Book excerpt: In an era of promising advances in cancer research, there are considerable and even alarming gaps in the fundamental knowledge and understanding of ovarian cancer. Researchers now know that ovarian cancer is not a single disease-several distinct subtypes exist with different origins, risk factors, genetic mutations, biological behaviors, and prognoses. However, persistent questions have impeded progress toward improving the prevention, early detection, treatment, and management of ovarian cancers. Failure to significantly improve morbidity and mortality during the past several decades is likely due to several factors, including the lack of research being performed by specific disease subtype, lack of definitive knowledge of the cell of origin and disease progression, and incomplete understanding of genetic and non-genetic risk factors. Ovarian Cancers examines the state of the science in ovarian cancer research, identifies key gaps in the evidence base and the challenges to addressing those gaps, considers opportunities for advancing ovarian cancer research, and examines avenues for translation and dissemination of new findings and communication of new information to patients and others. This study makes recommendations for public- and private-sector efforts that could facilitate progress in reducing the incidence of morbidity and mortality from ovarian cancers.

Download or read book Deciphering the Immunosuppressive Landscape of High grade Serous Ovarian Cancer written by Julian Smazynski and published by . This book was released on 2022 with total page pages. Available in PDF, EPUB and Kindle. Book excerpt: High-grade serous ovarian cancer (HGSC) remains the most common and lethal subtype of ovarian cancer with a 5-year survival rate of ~30%, highlighting an urgent need for new treatments. Cancer immunotherapy has emerged as an efficacious strategy aimed at harnessing the exquisite capabilities of our immune system to destroy malignant cells. However, the development of more effective immunotherapies is hampered by our limited understanding of the phenotype of bona fide tumor-reactive T cells versus irrelevant bystanders. Further, T cells that exhibit tumor specificity appear to encompass a tissue resident memory (TRM) phenotype but combat a harsh immunosuppressive tumor microenvironment, often leading to an exhausted phenotypic state and evasion of immune-mediated destruction. These insights have led to rapid clinical implementation of so-called "checkpoint blockade" therapies that re-invigorate T cell-mediated tumor destruction by blocking surface inhibitory receptors or ligands. Thus, by identifying the phenotype of prognostically favourable TRM T cells and the immunosuppressive networks they face, my thesis work tackles a critical challenge in designing the next generation of therapeutic interventions for this disease. To address this challenge, I hypothesized that (1) the TRM phenotype could be modulated for improving adoptive T cell therapy; (2) TRM TIL characterized by the co-expression of CD103, PD-1, and CD39 in HGSC provide improved prognostic benefit indicative of enriched tumor reactivity; (3) the TIGIT/CD155 signalling axis plays a crucial role in shaping the immunosuppressive landscape impeding TRM T cells in HGSC. Firstly, I developed methods for modulating the TRM phenotype on expanded human and murine T cells for adoptive cell therapy and assessed the therapeutic impact of these phenotypes. Secondly, we applied high-dimensional flow cytometry, single-cell sequencing, and multiplexed immunofluorescence to primary human HGSC specimens to explore the single-cell phenotypic profiles and prognostic significance of tumor-infiltrating T cells co-expressing three putative markers of tumor reactivity: CD39, CD103, and PD-1. These 'triple-positive' T cells exhibited a highly activated/exhausted phenotype and superior prognostic value relative to all other T-cell subsets, suggesting these markers enrich for tumor-reactive clones. Furthermore, these triple-positive cells exhibited heightened expression of the inhibitory checkpoint TIGIT, which plays a prominent role in tumor-mediated immune suppression. Finally, to explore the therapeutic implications of this finding, we investigated the relationship between the TIGIT signaling axis on TIL and prognosis in HGSC. Once again utilizing high-dimensional flow cytometry, multi-color histological imaging, and gene expression profiling we found T cells from HGSC frequently express TIGIT ex vivo and post-clinical expansion. Further, CD155, the dominant ligand for TIGIT, was largely expressed on malignant epithelium in HGSC and showed a negative association with immune infiltration. Thus, TRM T cells represents a compelling immunotherapeutic immune subset in HGSC and one that could be bolstered by immune checkpoint inhibition of the TIGIT/CD155 axis.

Download or read book Advances in Epithelial Ovarian Cancer Model Systems Microenvironmental Influences Therapy and Origins written by Viive Maarika Howell and published by Frontiers Media SA. This book was released on 2016-02-03 with total page 178 pages. Available in PDF, EPUB and Kindle. Book excerpt: This eBook provides a compendium of the current state-of-the-art in research tools for, and understanding of, the critical research areas in epithelial ovarian cancer (EOC) with a strong emphasis on (HG-SOC). Research areas covered include therapy response and development, microenvironmental influences and the etiology and progression of EOC. Ten articles detail established and novel in vivo and in vitro model systems. These include primary and immortalized cell culture in 2D and 3D as well as genetically engineered, transgenic, spontaneous, syngeneic, classical xenograft and patient derived xenograft mouse models. The generation of genetically engineered mouse models of HG-SOC has been a major dilemma as models with the oncogenic aberrations common in the human malignancy do not accurately recapitulate HG-SOC. Conversely, commonly used HG-SOC cell lines have been found to not harbor the expected genetic changes. These issues as well as the rapid acceptance of patient derived xenograft models are reviewed. Five articles discuss different aspects of the tumor microenvironment including its role in therapy resistance, disease progression and metastasis. Mutation of BRCA1/2 continues to be the best defined risk factor for HG-SOC. Three articles discuss BRCA-loss in the context of disease development, targeted therapies and changes in preventative measures proposed for mutation carriers in light of the recent advances in knowledge regarding the origins of this malignancy. An image of HG-SOC with reduced BRCA1 expression is featured on the cover (image by VM Howell). A major clinical issue for patients with HG-SOC is the development of therapy resistance. Five articles focus on therapy resistance and different ways to overcome resistance. Overall, this eBook is an outstanding resource to aid researchers design their programs of research and determine the most appropriate and up-to-date EOC model systems to address their research questions.

Download or read book The Intercellular Signaling Network in the Tumor Microenvironment of Ovarian High grade Serous Carcinoma written by Leah Sommerfeld and published by . This book was released on 2023 with total page 0 pages. Available in PDF, EPUB and Kindle. Book excerpt:

Download or read book Overcoming Ovarian Cancer Chemoresistance written by Goli Samimi and published by Academic Press. This book was released on 2020-11-06 with total page 190 pages. Available in PDF, EPUB and Kindle. Book excerpt: Overcoming Ovarian Cancer Chemoresistance presents non-overlapping review chapters that discuss the state of the field in overcoming chemoresistance of ovarian cancer and treatment options before and following recurrence, considering the genetic makeup of the ovarian cancer patient and her tumor. With the uptake of both germline and somatic gene testing, clinicians can obtain a more comprehensive understanding of ovarian tumors and this book provides information to link the genetic makeup of a tumor (or patient) with the best available treatment. The book discusses topics such as strategies to fight chemo-resistance in ovarian cancer, circulating DNA as a monitor of response, BRCA mutations, ovarian cancer stem cells, immunotherapy and vaccines. Additionally, it brings a list of promising agents at clinical and pre-clinical stage that will impact the treatment in the near future. This book is a valuable source for cancer researchers, oncologists and several members of biomedical field who need to understand how to battle chemoresistance in ovarian cancer. Provides a comprehensive view of both biological and genetic determinants of resistance, as well as technical approaches to monitor response Discusses genetic reversions as a unique alteration and a new field of study Includes a chapter on upcoming and promising agents that are in the pre-clinical and early clinical space, to set the stage for future directions in the field

Download or read book Ovarian Cancers written by Eric Pujade-Lauraine and published by Springer. This book was released on 2016-10-17 with total page 288 pages. Available in PDF, EPUB and Kindle. Book excerpt: This book provides an overview of the latest developments in the concepts and management of ovarian cancer. The new data presented throughout opens the way to radically different therapeutic approaches. Surgery remains the core of ovarian cancer treatment, but its ultimate goal and the standard surgical procedure have evolved, giving rise to the question of how to label expert centers for debulking surgery. Neo-adjuvant chemotherapy is becoming more popular and is also a new field for testing novel drug combinations. Over recent years, ovarian cancer management has embraced molecular biology. It is now more correct to talk about cancers of the ovary rather than ovarian cancer, since it is not a unique disease but several entities with different molecular drivers. The significant advances in drugs targeting the microenvironment or the tumor cell DNA repair mechanisms are presented in detail together with exciting future perspectives. All these advances would not have been possible without collaborative groups such as the GINECO group in France and their integration in wider clinical research networks at the European (ENGOT) and international (GCIG) level.

Download or read book Improving the Understanding of Platinum Sensitivity and the Tumour Microenvironment in High Grade Serous Ovarian Cancer written by Malcolm John Farquharson and published by . This book was released on 2018 with total page 0 pages. Available in PDF, EPUB and Kindle. Book excerpt:

Download or read book Assessment of Cytokine MRNA Expression Profiles in Tumor Microenvironment and Peripheral Blood Mononuclear Cells of Patients with High grade Serous Carcinoma of the Ovary written by Ulrika Ottander and published by . This book was released on 2017 with total page pages. Available in PDF, EPUB and Kindle. Book excerpt: Objective: Tumor establishment, metastatic spreading and poor survival in ovarian cancer is strongly associated with progressive derangement of the patientu2019s immune system. Accumulating evidence suggests that immune impairment is influenced by the production and presence of cytokines in the tumor microenvironment.Methods: Cytokine mRNA profiles in tumor tissue and peripheral blood mononuclear cells (PBMC) were analyzed in patients with high grade serous carcinoma (HGSC) of the ovary and compared to patients with benign ovarian conditions and controls with normal ovaries. Cytokine assessment was done by real-time quantitative RT-PCR and specific primers and probes for 12 cytokines-IFN-u03b3, IL-1u03b2, IL-2, IL-4, IL-6, IL-8, IL-10, IL-15, TNF-u03b1, TNF-u03b2/LTA, TGF-u03b21, and GM-CSF chosen to distinguish between cytotoxic Th1, humoral Th2, regulatory Th3/Tr1 and inflammatory responses.Results: The cytokine mRNA response in the HGSC patients was significantly up regulated compared to patients with benign ovarian conditions and normal ovary controls confirming the immunogenicity of HGSC and implying immune recognition and reaction locally in the tumor microenvironment and systemically in the peripheral blood. There was an up-regulation of inflammatory and inhibitory cytokine mRNA promoting tumor progression, T-regulatory cell priming and T-regulatory cell-mediated immune suppression. In contrast, there was an inability to mount the crucially important IFN gamma response needed for upregulation of the cytotoxic anti-tumor response in the local microenvironment. In addition, systemic IL-4- mediated Th2 response prevailed in the peripheral blood deviating the systemic defense towards humoral immunity.Conclusions: Taken together, these results suggest local and systemic cytokine cooperation promoting tumor survival, progression and immune escape. Our study confirms and extends previous investigations and contributes to the evaluation of potential cytokine candidates for diagnostic cytokine mRNA profiles and for future therapeutic interventions based on cytokine inhibition.

Download or read book WHO Classification of Tumours of Female Reproductive Organs written by Robert J. Kurman and published by World Health Organization. This book was released on 2014 with total page 307 pages. Available in PDF, EPUB and Kindle. Book excerpt: WHO Classification of Tumours of Female Reproductive Organs is the sixth volume in the 4th Edition of the WHO series on histological and genetic typing of human tumours. This authoritative, concise reference book provides an international standard for oncologists and pathologists and will serve as an indispensable guide for use in the design of studies monitoring response to therapy and clinical outcome. Diagnostic criteria, pathological features, and associated genetic alterations are described in a strictly disease-oriented manner. Sections on all recognized neoplasms and their variants include new ICD-O codes, epidemiology, clinical features, macroscopy, pathology, genetics, and prognosis and predictive factors. The book, prepared by 91 authors from 19 countries, contains more than 400 colour images and tables, and more than 2100 references

Download or read book Exploring the Tumor and Premetastatic Microenvironment of the Ovary written by Curtis McCloskey and published by . This book was released on 2019 with total page pages. Available in PDF, EPUB and Kindle. Book excerpt: Ovarian cancers are the most lethal gynecological malignancies, responsible for more than 150,000 deaths around the globe annually. Among ovarian cancers, high-grade serous ovarian cancer has a 5-year survival rate of only 40%. This poor survival is due to a widespread lack of understanding of this disease, from suboptimal prevention and screening methods to failures in treatment. Moving towards novel prevention and treatment methods requires better models of ovarian cancer that phenotypically and genetically recapitulate the features of ovarian cancers that are seen clinically. This thesis highlights the characterization of a novel syngeneic model of high-grade serous ovarian cancer that exhibits the growth, expression profile, histology, and a tumor-initiating cell population that closely resembles human disease. We expand on our initial characterization of the STOSE model in a proof-of-principle study using deep learning of second-harmonic generation and two-photon-excited-fluorescence images to classify normal compared to cancerous tissues. The use of deep learning for image classification based on extracellular matrix and cellular structure could have robust application to complementing common histological examination of tissues and in treatment planning. Building on the changes in structure found in normal compared to cancerous ovarian tissue and recent research that showed age-associated fibrosis develops in murine ovaries, we assessed the non-hereditary ovarian cancer risk factors of age and ovulation number for their effects in altering ovarian tissue structure. This thesis concludes with the first evidence of ovarian fibrosis in non-pathological post-menopausal human ovaries. We show that ovarian fibrosis correlates with the development of a pre-metastatic (tumor-permissive) niche, revealing a novel avenue of research into ovarian cancer risk. Interestingly, age-associated fibrosis could be prevented or reversed by metformin use, revealing a possible mechanism for the previously identified ovarian cancer risk reduction seen with metformin use and further supporting the use of metformin for ovarian cancer prevention.

Download or read book Tumor Microenvironment and Therapeutic Resistance in Gynecologic Malignancies written by Xia Bai Rong and published by Frontiers Media SA. This book was released on 2023-02-02 with total page 132 pages. Available in PDF, EPUB and Kindle. Book excerpt:

Download or read book Differential Expression at the Proteomic Level of Stem cell Markers and Other Gene Markers in High grade Serous Vs Other Subtypes of Ovarian Cancer written by Lipilekha Mukherjee and published by . This book was released on 2017 with total page 93 pages. Available in PDF, EPUB and Kindle. Book excerpt: Ovarian carcinoma is the most lethal neoplasm and the fifth leading cause of death in women due to gynecological malignancies. It is estimated that there are 225,000 new cases diagnosed and 140,000 deaths occurring annually worldwide. Among the different subtypes, widely heterogeneous high-grade serous ovarian cancer (HGSOC) poses a great challenge to modern chemotherapy due to its high recurrence rate and resistance to standard treatments. Both of those causes are linked to the presence of a small subpopulation of cancer stem cells (CSCs) in the tumor microenvironment. Recent studies suggest that survival timeline and disease recurrence are linked to the variable expression of both cancer CSC and other gene biomarkers in cancer cells. Therefore, using Western blot and immunohistochemistry analyses, we assessed the expression of a host of CSC and other gene products at the whole-cell level in total protein extracts and sub-cellular levels in PFA-fixed cells from three HGSOC and five non-HGSOC cell lines. We found that no CSCmarkers were expressed in monolayer two-dimensional cultures that could differentiate HGSOCs from non-HGSOCs. In fact, no CSC-biomarker proteins were detected in any of the subtypes of the cancer-cell lines in our studies. Upon assessing other gene biomarkers at the proteomic level, we observed prominent differential expression patterns among the HGSOC and non-HGSOC subtypes and even within a subtype but no definite pattern to distinguish HGSOCs from non- HGSOCs. In conclusion, determining a differential protein expression profile in subtypes of ovarian cancer requires much further attention in order to provide earlier detection methods and personalized treatment options for patients.

Download or read book Holland Frei Cancer Medicine written by Robert C. Bast, Jr. and published by John Wiley & Sons. This book was released on 2017-03-10 with total page 2004 pages. Available in PDF, EPUB and Kindle. Book excerpt: Holland-Frei Cancer Medicine, Ninth Edition, offers a balanced view of the most current knowledge of cancer science and clinical oncology practice. This all-new edition is the consummate reference source for medical oncologists, radiation oncologists, internists, surgical oncologists, and others who treat cancer patients. A translational perspective throughout, integrating cancer biology with cancer management providing an in depth understanding of the disease An emphasis on multidisciplinary, research-driven patient care to improve outcomes and optimal use of all appropriate therapies Cutting-edge coverage of personalized cancer care, including molecular diagnostics and therapeutics Concise, readable, clinically relevant text with algorithms, guidelines and insight into the use of both conventional and novel drugs Includes free access to the Wiley Digital Edition providing search across the book, the full reference list with web links, illustrations and photographs, and post-publication updates

Download or read book Cancer Associated Fibroblasts Provide a Cancer Stem Cell Niche that Leads to Disease Relapse in Ovarian Cancer written by Yiming Fang (Biochemist) and published by . This book was released on 2023 with total page 0 pages. Available in PDF, EPUB and Kindle. Book excerpt: Epithelial ovarian cancer is the most lethal gynecologic malignancy with a 5-year survival rate of only 48%. While most ovarian cancer patients respond to chemotherapy initially, frequent relapse (~80%) and development of chemoresistance result in poor patient outcomes. Cancer stem cells (CSCs) consist of a small subpopulation in the tumor that are capable of surviving from chemotherapy and causing tumor relapse. Using patient specimens and in vitro models, we determined that CSCs are enriched by cancer associated fibroblasts (CAFs) after chemotherapy. Cancer associated fibroblasts (CAFs) are a major constituent of the ovarian cancer tumor microenvironment and are highly enriched in the residual tumors following chemotherapy. Therefore, we studied the mechanism by which CAFs promote ovarian cancer chemoresistance and disease relapse. CAFs isolated from ovarian cancer patient tumors were used in heterotypic 2D or 3D coculture systems with high-grade serous ovarian cancer cell lines or with patient-derived ovarian cancer cells to study their effect on CSCs and chemoresistance. Matched pre-and post-chemotherapy patient tumors were used to confirm our findings. CAFs significantly increased adjacent cancer cell resistance to carboplatin by enriching CSCs. Pre-coculture with CAFs increased in vivo tumor initiation capacity of the ovarian cancer cells by 10-fold in limiting dilution assay analysis (ELDA) in mice. The CSC-CAF crosstalk responsible for CSC induction was found to be mediated by Wnt5a signaling. CRISPR knockdown of Wnt5a in CAFs or treatment with a specific Wnt5a inhibitor abrogated the induction of CSCs by CAFs. Only cancer cells with ROR2, a Wnt coreceptor, respond to Wnt5a signaling triggered by CAFs and developed into CSCs. Responders were found to signal through a non-canonical Wnt pathway involving the coreceptor ROR2, protein kinase C (PKC), and cAMP Responsive Element Binding Protein 1 (CREB1). Inhibition of each of them prevented CSC induction and functional rescue experiments were performed to confirm the sequence of the Wnt5a-ROR2-PKC-CREB1 axis. Treatment of mouse xenografts, established by co-injection of CAFs and ovarian cancer cells, with the Wnt5a inhibitor sensitized them to carboplatin, and eliminated the CSCs in the residual tumors. Our results indicate that CAF-derived Wnt5a is instrumental in ovarian cancer CSC growth and maintenance. Targeting Wnt5a in tumor effectively prevents tumor relapse after cytotoxic chemotherapy by destroying suitable CSC-enriching microenvironment. In the long term, our studies will broaden the understanding of the mechanism of CSC maintenance by the tumor microenvironment and contribute towards the development of novel therapeutic approaches to prevent ovarian cancer chemoresistance and relapse.