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The Journal of Obstetrics and... Nov 2020This review aims to analyze the pathological aspects, diagnosis and treatment of rare mesenchymal uterine tumors. (Review)
Review
OBJECTIVE
This review aims to analyze the pathological aspects, diagnosis and treatment of rare mesenchymal uterine tumors.
METHODS
On August 2019, a systematic review of the literature was done on Pubmed, MEDLINE, Scopus, and Google Scholar search engines. The systematic review was carried out in agreement with the Preferred Reporting Items for Systematic Reviews and Meta-Analyzes statement (PRISMA). The following words and key phrases have been searched: "endometrial stromal sarcoma", "low-grade endometrial stromal sarcoma", "high-grade endometrial stromal sarcoma", "uterine sarcoma", "mesenchymal uterine tumors" and "uterine stromal sarcoma". Across these platforms and research studies, five main aspects were analyzed: the biological characteristics of the neoplasms, the number of cases, the different therapeutic approaches used, the follow-up and the oncological outcomes.
RESULTS
Of the 94 studies initially identified, 55 were chosen selecting articles focusing on endometrial stromal sarcoma. Of these fifty-five studies, 46 were retrospective in design, 7 were reviews and 2 randomized phases III trials.
CONCLUSION
Endometrial stromal sarcomas are rare mesenchymal uterine neoplasms and surgery represents the standard treatment. For uterus-limited disease, the remove en bloc with an intact resection of the tumor (without the use of morcellation) is strongly recommended. For advanced-stage disease, the standard surgical treatment is adequate cytoreduction with metastatectomy. Pelvic and para-aortic lymphadenectomy is not recommended in patients with Low-grade Endometrial Stromal Sarcoma (ESS), while is not clear whether cytoreduction of advanced tumors improves patient survival in High-grade ESS. Administration of adjuvant radiotherapy or chemotherapy is not routinely used and its role is still debated.
Topics: Endometrial Neoplasms; Female; Humans; Retrospective Studies; Sarcoma, Endometrial Stromal; Uterine Neoplasms
PubMed: 32830415
DOI: 10.1111/jog.14436 -
Cancer Treatment and Research... 2022Squamous cell cancer of the head and neck (HNSCC) is the sixth most common cancer and is associated with significant morbidity and mortality. The tumor microenvironment... (Review)
Review
Squamous cell cancer of the head and neck (HNSCC) is the sixth most common cancer and is associated with significant morbidity and mortality. The tumor microenvironment for HNSCC is a complex interplay of immune cells, stromal cells, and cytokines amongst others. Immunotherapy acts as an effective antineoplastic agent by influencing this complex environment and includes immune checkpoint inhibitors (ICI). ICI have been approved in the frontline setting for recurrent and metastatic (R/M) HNSCC as well as platinum-refractory (second line) R/M HNSCC. However, recent clinical studies highlight that the response to immunotherapy varies, and different ICI, as well as different combination strategies play a crucial role in augmenting the efficacy of immunotherapy. An in-depth analysis and focused study of the immune contexture in patients with HNSCC receiving ICI remains critical. Many novel immunotherapies including CAR-T cell therapy, oncolytic virus therapy, and vaccines are underway. Ongoing trials are testing ICI in the neoadjuvant and adjuvant settings. Furthermore, identifying better biomarkers to target population that benefits from immunotherapy is of paramount importance. Pioneering the optimal combination regimen utilizing new novel immunotherapy has recently become a paradigm shift in the HNSCC treatment landscape. Herein, we summarize the clinical development with all ongoing clinical trials of immunotherapy in HNSCC.
Topics: Humans; Squamous Cell Carcinoma of Head and Neck; Neoplasm Recurrence, Local; Immunotherapy; Head and Neck Neoplasms; Carcinoma, Squamous Cell; Tumor Microenvironment
PubMed: 36279709
DOI: 10.1016/j.ctarc.2022.100649 -
Cells Dec 2021Communication between cancer cells and the surrounding stromal cells of the tumor microenvironment (TME) plays a key role in promoting metastasis, which is the major... (Review)
Review
Communication between cancer cells and the surrounding stromal cells of the tumor microenvironment (TME) plays a key role in promoting metastasis, which is the major cause of cancer death. Small membrane-bound particles called extracellular vesicles (EVs) are released from both cancer and stromal cells and have a key role in mediating this communication through transport of cargo such as various RNA species (mRNA, miRNA, lncRNA), proteins, and lipids. Tumor-secreted EVs have been observed to induce a pro-tumorigenic phenotype in non-malignant cells of the stroma, including fibroblasts, endothelial cells, and local immune cells. These cancer-associated cells then drive metastasis by mechanisms such as increasing the invasiveness of cancer cells, facilitating angiogenesis, and promoting the formation of the pre-metastatic niche. This review will cover the role of EV-mediated signaling in the TME during metastasis and highlight the therapeutic potential of targeting these pathways to develop biomarkers and novel treatment strategies.
Topics: Cell Communication; Endothelial Cells; Extracellular Vesicles; Fibroblasts; Humans; Neoplasm Metastasis; Neoplasms; Stromal Cells; Tumor Microenvironment
PubMed: 34943937
DOI: 10.3390/cells10123429 -
Journal of Mammary Gland Biology and... Jun 2021Years of investigation have shed light on a theory in which breast tumor epithelial cells are under the effect of the stromal microenvironment. This review aims to... (Review)
Review
Years of investigation have shed light on a theory in which breast tumor epithelial cells are under the effect of the stromal microenvironment. This review aims to discuss recent findings concerning the phenotypic and functional characteristics of cancer associated fibroblasts (CAFs) and their involvement in tumor evolution, as well as their potential implications for anti-cancer therapy. In this manuscript, we reviewed that CAFs play a fundamental role in initiation, growth, invasion, and metastasis of breast cancer, and also serve as biomarkers in the clinical diagnosis, therapy, and prognosis of this disease.
Topics: Breast; Breast Neoplasms; Cancer-Associated Fibroblasts; Carcinogenesis; Disease-Free Survival; Female; Humans; Neoplasm Invasiveness; Neoplasm Recurrence, Local; Prognosis; Tumor Microenvironment
PubMed: 33398516
DOI: 10.1007/s10911-020-09475-y -
International Journal of Molecular... Feb 2021The tumor-microenvironment (TME) is an amalgamation of various factors derived from malignant cells and infiltrating host cells, including cells of the immune system.... (Review)
Review
The tumor-microenvironment (TME) is an amalgamation of various factors derived from malignant cells and infiltrating host cells, including cells of the immune system. One of the important factors of the TME is microRNAs (miRs) that regulate target gene expression at a post transcriptional level. MiRs have been found to be dysregulated in tumor as well as in stromal cells and they emerged as important regulators of tumorigenesis. In fact, miRs regulate almost all hallmarks of cancer, thus making them attractive tools and targets for novel anti-tumoral treatment strategies. Tumor to stroma cell cross-propagation of miRs to regulate protumoral functions has been a salient feature of the TME. MiRs can either act as tumor suppressors or oncogenes (oncomiRs) and both miR mimics as well as miR inhibitors (antimiRs) have been used in preclinical trials to alter cancer and stromal cell phenotypes. Owing to their cascading ability to regulate upstream target genes and their chemical nature, which allows specific pharmacological targeting, miRs are attractive targets for anti-tumor therapy. In this review, we cover a recent update on our understanding of dysregulated miRs in the TME and provide an overview of how these miRs are involved in current cancer-therapeutic approaches from bench to bedside.
Topics: Animals; Antagomirs; Clinical Trials as Topic; Drug Delivery Systems; Drug Resistance, Neoplasm; Gene Expression Regulation, Neoplastic; Humans; Immunotherapy; MicroRNAs; Molecular Targeted Therapy; Neoplasms; Oligonucleotides; Tumor Microenvironment
PubMed: 33672261
DOI: 10.3390/ijms22042210 -
Nature Reviews. Cancer Aug 2019YAP and TAZ are transcriptional activators pervasively induced in several human solid tumours and their functions in cancer cells are the focus of intense investigation.... (Review)
Review
YAP and TAZ are transcriptional activators pervasively induced in several human solid tumours and their functions in cancer cells are the focus of intense investigation. These studies established that YAP and TAZ are essential to trigger numerous cell-autonomous responses, such as sustained proliferation, cell plasticity, therapy resistance and metastasis. Yet tumours are complex entities, wherein cancer cells are just one of the components of a composite "tumour tissue". The other component, the tumour stroma, is composed of an extracellular matrix with aberrant mechanical properties and other cell types, including cancer-associated fibroblasts and immune cells. The stroma entertains multiple and bidirectional interactions with tumour cells, establishing dependencies essential to unleash tumorigenesis. The molecular players of such interplay remain partially understood. Here, we review the emerging role of YAP and TAZ in choreographing tumour-stromal interactions. YAP and TAZ act within tumour cells to orchestrate responses in stromal cells. Vice versa, YAP and TAZ in stromal cells trigger effects that positively feed back on the growth of tumour cells. Recognizing YAP and TAZ as a hub of the network of signals exchanged within the tumour microenvironment provides a fresh perspective on the molecular principles of tumour self-organization, promising to unveil numerous new vulnerabilities.
Topics: Adaptor Proteins, Signal Transducing; Animals; Carcinogenesis; Cell Adhesion; Cell Proliferation; Extracellular Matrix; Humans; Mice; Neoplasm Metastasis; Neoplasms; Phenotype; Signal Transduction; Stromal Cells; Trans-Activators; Transcription Factors; Transcriptional Coactivator with PDZ-Binding Motif Proteins; Tumor Microenvironment; YAP-Signaling Proteins
PubMed: 31270418
DOI: 10.1038/s41568-019-0168-y -
Frontiers in Immunology 2020The intricate interplay between malignant cells and host cellular and non-cellular components play crucial role in different stages of tumor development, progression,... (Review)
Review
The intricate interplay between malignant cells and host cellular and non-cellular components play crucial role in different stages of tumor development, progression, and metastases. Tumor and stromal cells communicate to each other through receptors such as integrins and secretion of signaling molecules like growth factors, cytokines, chemokines and inflammatory mediators. Chemokines mediated signaling pathways have emerged as major mechanisms underlying multifaceted roles played by host cells during tumor progression. In response to tumor stimuli, host cells-derived chemokines further activates signaling cascades that support the ability of tumor cells to invade surrounding basement membrane and extra-cellular matrix. The host-derived chemokines act on endothelial cells to increase their permeability and facilitate tumor cells intravasation and extravasation. The tumor cells-host neutrophils interaction within the vasculature initiates chemokines driven recruitment of inflammatory cells that protects circulatory tumor cells from immune attack. Chemokines secreted by tumor cells and stromal immune and non-immune cells within the tumor microenvironment enter the circulation and are responsible for formation of a "pre-metastatic niche" like a "soil" in distant organs whereby circulating tumor cells "seed' and colonize, leading to formation of metastatic foci. Given the importance of host derived chemokines in cancer progression and metastases several drugs like Mogamulizumab, Plerixafor, Repertaxin among others are part of ongoing clinical trial which target chemokines and their receptors against cancer pathogenesis. In this review, we focus on recent advances in understanding the complexity of chemokines network in tumor microenvironment, with an emphasis on chemokines secreted from host cells. We especially summarize the role of host-derived chemokines in different stages of metastases, including invasion, dissemination, migration into the vasculature, and seeding into the pre-metastatic niche. We finally provide a brief description of prospective drugs that target chemokines in different clinical trials against cancer.
Topics: Animals; Cancer-Associated Fibroblasts; Cell Communication; Chemokines; Disease Management; Epithelial-Mesenchymal Transition; Extracellular Matrix; Humans; Immunity, Innate; Molecular Targeted Therapy; Neoplasm Invasiveness; Neoplasm Metastasis; Neoplasm Staging; Neoplasms; Stromal Cells; Tumor Microenvironment
PubMed: 33414786
DOI: 10.3389/fimmu.2020.598532 -
NMR in Biomedicine Oct 2019Because of the spatial and temporal heterogeneities of cancers, technologies to investigate cancer cells and the consequences of their interactions with abnormal... (Review)
Review
Because of the spatial and temporal heterogeneities of cancers, technologies to investigate cancer cells and the consequences of their interactions with abnormal physiological environments, such as hypoxia and acidic extracellular pH, with stromal cells, and with the extracellular matrix, under controlled conditions, are valuable to gain insights into the functioning of cancers. These insights can lead to an understanding of why cancers invade and metastasize, and identify effective treatment strategies. Here we have provided an overview of the applications of MRI/MRS/MRSI to investigate intact perfused cancer cells, their metabolism and invasion, and their interactions with stromal cells and the extracellular matrix.
Topics: Cell Communication; Humans; Magnetic Resonance Imaging; Magnetic Resonance Spectroscopy; Neoplasm Invasiveness; Neoplasms; Perfusion; Stromal Cells
PubMed: 30693605
DOI: 10.1002/nbm.4053 -
Clinical & Translational Oncology :... Feb 2023Metastasis is the leading cause of mortality related to cancer. In the course of metastasis, cancer cells detach from the primary tumor, enter the circulation,... (Review)
Review
Metastasis is the leading cause of mortality related to cancer. In the course of metastasis, cancer cells detach from the primary tumor, enter the circulation, extravasate at secondary sites, and colonize there. All of these steps are rate limiting and decrease the efficiency of metastasis. Prior to their arrival, tumor cells can modify the secondary sites. These favorable microenvironments increase the probability of successful dissemination and are referred to as pre-metastatic niches. Cancer cells use different mechanisms to induce and maintain these niches, among which immune cells play prominent roles. The immune system, including innate and adaptive, enhances recruitment, extravasation, and colonization of tumor cells at distant sites. In addition to immune cells, stromal cells can also contribute to forming pre-metastatic niches. This review summarizes the pro-metastatic responses conducted by immune cells and the assistance of stromal cells and endothelial cells in the induction of pre-metastatic niches.
Topics: Humans; Endothelial Cells; Neoplasms; Carcinogenesis; Stromal Cells; Neoplasm Metastasis; Tumor Microenvironment
PubMed: 36136272
DOI: 10.1007/s12094-022-02950-4 -
Annals of Diagnostic Pathology Aug 2022Endometrial stromal sarcoma (ESS) is the second most common uterine mesenchymal neoplasm. ESS can arise from extrauterine locations without any uterine involvement and... (Meta-Analysis)
Meta-Analysis Review
Endometrial stromal sarcoma (ESS) is the second most common uterine mesenchymal neoplasm. ESS can arise from extrauterine locations without any uterine involvement and is called extrauterine ESS (EESS). The epidemiological features of EESS are not well-known. Moreover, the factors affecting its outcome have not been systemically studied. The treatment of EESS closely follows that of uterine ESS, comprised of different combinations of surgical management, hormone therapy, chemotherapy, and radiation therapy. However, the effectiveness of different treatment protocols for EESS has not been studied. Here, we have performed a systematic review of all reported cases of EESS in the English literature. We further performed a meta-analysis of the outcome data and investigated how the patients' age, tumor site, tumor size, and management affect the overall and progression-free survival of the patients. We found that tumor site and mode of treatment significantly affected the overall survival and progression-free survival of the patients. Tumor size significantly affected overall survival but not progression-free survival, while the age at diagnosis did not affect patient outcome. As far as we know, ours is the first systematic study of this rare malignancy with an emphasis on outcome analysis.
Topics: Endometrial Neoplasms; Female; Humans; Sarcoma, Endometrial Stromal
PubMed: 35569210
DOI: 10.1016/j.anndiagpath.2022.151966