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Archives of Pathology & Laboratory... Oct 2008Hepatic angiomyolipoma is a rare, benign, hepatic mesenchymal neoplasm found in both males and females, and most commonly in adult females. Angiomyolipoma occurs most... (Review)
Review
Hepatic angiomyolipoma is a rare, benign, hepatic mesenchymal neoplasm found in both males and females, and most commonly in adult females. Angiomyolipoma occurs most commonly in the kidneys. The liver represents the second most frequent site of involvement. Hepatic angiomyolipomas are composed of varying amounts of smooth muscle cells, adipose tissue, and vessels. The smooth muscle cell component is the most specific to the diagnosis. The smooth muscle cells can have varying morphologies and are positive for homatropine methylbromide-45 but are negative for hepatocyte paraffin 1 and S100 protein. The definitive diagnostic study remains the histologic examination of the surgically resected lesion coupled with immunohistochemical stains. The differential diagnosis includes hepatocellular carcinoma, hepatic adenoma, leiomyoma, hepatoblastoma, melanoma, and gastrointestinal stromal tumor. The immunohistochemical staining pattern differentiates this lesion from other malignant and benign liver lesions. If the diagnosis of hepatic angiomyolipoma has been made, it can be followed conservatively or surgically resected.
Topics: Angiomyolipoma; Antigens, Neoplasm; Female; Humans; Liver Neoplasms; MART-1 Antigen; Male; Melanoma-Specific Antigens; Neoplasm Proteins; S100 Proteins
PubMed: 18834230
DOI: 10.5858/2008-132-1679-HA -
Journal of Internal Medicine Feb 2013Tumour progression requires the activation of a tumour and stromal cell-driven angiogenic programme, and the targeting of this process demonstrates an impact on tumour... (Review)
Review
Tumour progression requires the activation of a tumour and stromal cell-driven angiogenic programme, and the targeting of this process demonstrates an impact on tumour growth and progression. The results of preclinical studies have demonstrated a proinvasive/metastatic effect of antiangiogenic treatments with recent evidence supporting a contribution of the stroma to tumour aggressiveness and the short-term effects of antivascular endothelial growth factor therapy. Furthermore, hypoxia-dependent and -independent factors are considered as driving forces for tumour cell escape by altering both the tumour cells themselves and the stroma. This tumour-stromal cell alliance should be taken into consideration for the development of innovative therapeutic options targeting both tumour components to improve clinical benefits for cancer patients.
Topics: Angiogenesis Inhibitors; Humans; Hypoxia; Neoplasm Metastasis; Neoplasms; Neovascularization, Pathologic; Stromal Cells; Vascular Endothelial Growth Factor A
PubMed: 23198797
DOI: 10.1111/joim.12018 -
International Journal of Molecular... Feb 2021Despite improvements in therapy and management, cancer represents and remains a major cause of mortality and morbidity worldwide. Although genetics serve an important... (Review)
Review
Despite improvements in therapy and management, cancer represents and remains a major cause of mortality and morbidity worldwide. Although genetics serve an important role in tumorigenesis and tumour progression, the tumour microenvironment (TME) in solid tumours is also important and has been indicated to contribute to these processes. Stromal cell‑derived factors (SDFs) represent an important family within the TME. The family includes SDF‑1, SDF‑2, SDF2‑like 1 (SDF2L1), SDF‑3, SDF‑4 and SDF‑5. SDF‑1 has been demonstrated to act as a positive regulator in a number of types of tumour, such as oesophago‑gastric, pancreatic, lung, breast, colorectal and ovarian cancer, while the biology and functions of other members of the SDF family, including SDF‑2, SDF2L1, SDF‑4 and SDF‑5, in cancer are different, complex and controversial, and remain mainly unknown. Full identification and understanding of the SDFs across multiple types of cancer is required to elucidate their function and establish potential key targets in cancer.
Topics: Humans; Intercellular Signaling Peptides and Proteins; Neoplasm Proteins; Neoplasms; Tumor Microenvironment
PubMed: 33416125
DOI: 10.3892/ijmm.2020.4811 -
Cancer Science Oct 2018Exosomes are representative extracellular vesicles (EV) derived from multivesicular endosomes (MVE) and have been described as new particles in the communication of... (Review)
Review
Exosomes are representative extracellular vesicles (EV) derived from multivesicular endosomes (MVE) and have been described as new particles in the communication of neighborhood and/or distant cells by serving as vehicles for transfer between cells of membrane and cytosolic proteins, lipids, and nucleotides including micro (mi) RNAs. Exosomes from immune cells and tumor cells act in part as a regulator in tumor immunology. CD8 T cells that show potent cytotoxic activity against tumor cells reside as an inactive naïve form in the T-cell zone of secondary lymphoid organs. Once receiving tumor-specific antigenic stimulation by dendritic cells (DC), CD8 T cells are activated and differentiated into effector CTL. Subsequently, CTL circulate systemically, infiltrate into tumor lesions through the stromal neovasculature where mesenchymal stromal cells, for example, mesenchymal stem cells (MSC) and cancer-associated fibroblasts (CAF), abundantly exist, destroy mesenchymal tumor stroma in an exosome-mediated way, go into tumor parenchyma, and attack tumor cells by specific interaction. DC-derived and regulatory T (Treg) cell-derived exosomes, respectively, promote and inhibit CTL generation in this setting. In this review, we describe the roles of exosomes from immune cells and tumor cells on the regulation of tumor progression.
Topics: Antigens, Neoplasm; Cytotoxicity, Immunologic; Disease Progression; Exosomes; Humans; Immunity, Cellular; Neoplasm Invasiveness; Neoplasms; Signal Transduction
PubMed: 29999574
DOI: 10.1111/cas.13735 -
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 -
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 -
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 -
Japanese Journal of Clinical Oncology Feb 2024Esophageal cancer is common worldwide, including in Japan, and its major histological subtype is squamous cell carcinoma. However, there are some rare esophageal... (Review)
Review
Esophageal cancer is common worldwide, including in Japan, and its major histological subtype is squamous cell carcinoma. However, there are some rare esophageal cancers, including neuroendocrine neoplasm, gastrointestinal stromal tumor, carcinosarcoma and malignant melanoma. The biological and clinical features of these cancers differ from those of esophageal squamous cell carcinoma. Therefore, different treatment strategies are needed for these cancers but are based on limited evidence. Neuroendocrine neoplasm is mainly divided into neuroendocrine tumor and neuroendocrine carcinoma by differentiation and the Ki-67 proliferation index or mitotic index. Epidemiologically, the majority of esophageal neuroendocrine neoplasms are neuroendocrine carcinoma. The treatment of neuroendocrine carcinoma is similar to that of small cell lung cancer, which has similar morphological and biological features. Gastrointestinal stromal tumor is known to be associated with alterations in the c-KIT and platelet-derived growth factor receptor genes and, if resectable, is treated in accordance with the modified Fletcher classification. Carcinosarcoma is generally resistant to both chemotherapy and radiotherapy and requires multimodal treatments such as surgery plus chemotherapy to achieve cure. Primary malignant melanoma is resistant to cytotoxic chemotherapy, but immune checkpoint inhibitors have recently demonstrated efficacy for malignant melanoma of the esophagus. This review focuses on the current status and future perspectives for rare cancer of the esophagus.
Topics: Humans; Esophageal Neoplasms; Esophageal Squamous Cell Carcinoma; Melanoma; Carcinoma, Neuroendocrine; Gastrointestinal Stromal Tumors; Carcinosarcoma
PubMed: 37861097
DOI: 10.1093/jjco/hyad144 -
Cancer Metastasis Reviews Jun 2013Cancer is a systemic disease encompassing multiple components of both tumor cells themselves and host stromal cells. It is now clear that stromal cells in the tumor... (Review)
Review
Cancer is a systemic disease encompassing multiple components of both tumor cells themselves and host stromal cells. It is now clear that stromal cells in the tumor microenvironment play an important role in cancer development. Molecular events through which reactive stromal cells affect cancer cells can be defined so that biomarkers and therapeutic targets can be identified. Cancer-associated fibroblasts (CAFs) make up the bulk of cancer stroma and affect the tumor microenvironment such that they promote cancer initiation, angiogenesis, invasion, and metastasis. In breast cancer, CAFs not only promote tumor progression but also induce therapeutic resistance. Accordingly, targeting CAFs provides a novel way to control tumors with therapeutic resistance. This review summarizes the current understandings of tumor stroma in breast cancer with a particular emphasis on the role of CAFs and the therapeutic implications of CAFs. In addition, the effects of other stromal components such as endothelial cells, macrophages, and adipocytes in breast cancer are also discussed. Finally, we describe the biologic markers to categorize patients into a specific and confirmed subtype for personalized treatment.
Topics: Breast Neoplasms; Drug Resistance, Neoplasm; Epigenesis, Genetic; Female; Fibroblasts; Humans; Neoplasm Staging; Prognosis; Stromal Cells; Tumor Microenvironment
PubMed: 23114846
DOI: 10.1007/s10555-012-9415-3 -
Cancer Science Oct 2017Tumor metastasis is the main cause of cancer-related death. Understanding the molecular mechanisms underlying tumor metastasis is crucial to control this fatal disease.... (Review)
Review
Tumor metastasis is the main cause of cancer-related death. Understanding the molecular mechanisms underlying tumor metastasis is crucial to control this fatal disease. Several molecular pathways orchestrate the complex biological cell events during a metastatic cascade. It is now well known that bidirectional interaction between tumor cells and their microenvironment, including tumor stroma, is important for tumor progression and metastasis. Tumor stromal cells, which acquire their specific characteristics in the tumor microenvironment, accelerate tumor malignancy. The formation of new blood vessels, termed as tumor angiogenesis, is a requirement for tumor progression. Tumor blood vessels supply nutrients and oxygen and also provide the route for metastasis. Tumor endothelial cells, which line tumor blood vessels, also exhibit several altered phenotypes compared with those of their normal counterparts. Recent studies have emphasized "angiocrine factors" that are released from tumor endothelial cells and promote tumor progression. During intravasation, tumor cells physically contact tumor endothelial cells and interact with them by juxtacrine and paracrine signaling. Recently, we observed that in highly metastatic tumors, tumor endothelial cells interact with tumor cells by secretion of a small leucine-rich repeat proteoglycan known as biglycan. Biglycan from tumor endothelial cells stimulates the tumor cells to metastasize. In the present review, we highlight the role of tumor stromal cells, particularly endothelial cells, in the initial steps of tumor metastasis.
Topics: Animals; Biglycan; Disease Progression; Endothelial Cells; Humans; Neoplasm Metastasis; Neoplasms; Neovascularization, Pathologic; Paracrine Communication; Signal Transduction; Tumor Microenvironment
PubMed: 28763139
DOI: 10.1111/cas.13336