Embryonal Carcinoma Stem Cells
Carcinoma, Embryonal
Teratoma
Tretinoin
Cell Differentiation
Neoplastic Stem Cells
Stem Cells
Carcinoma
Embryonic Stem Cells
Stem Cell Transplantation
Carcinoma, Squamous Cell
Carcinoma, Hepatocellular
Human immunodeficiency virus-associated Hodgkin's disease derives from post-germinal center B cells. (1/294)
Human immunodeficiency virus-associated Hodgkin's disease (HIV-HD) displays several peculiarities when compared with HD of the general population. These include overrepresentation of clinically aggressive histologic types and frequent infection of Reed-Sternberg (RS) cells by Epstein-Barr virus (EBV). Recently, we have reported that the histogenesis of HD of the general population may be assessed by monitoring the expression pattern of BCL-6, a transcription factor expressed in germinal center (GC) B cells, and of CD138/syndecan-1 (syn-1), a proteoglycan associated with post-GC, terminal B-cell differentiation. In this study, we have applied these two markers to the study of HIV-HD histogenesis and correlated their expression status to the virologic features of this disease. We have found that RS cells of all histologic categories of HIV-HD consistently display the BCL-6(-)/syn-1(+) phenotype and thus reflect post-GC B cells. Although BCL-6(-)/syn-1(+) RS cells of HIV-HD express CD40, they are not surrounded by CD40 ligand-positive (CD40L+) reactive T lymphocytes, which, in HD of the general population, are thought to regulate the disease phenotype through CD40/CD40L interactions. Conversely, RS cells of virtually all HIV-HD express the EBV-encoded latent membrane protein 1 (LMP1), which, being functionally homologous to CD40, may contribute, at least in part, to the modulation of the HIV-HD phenotype. (+info)The expression and function of cadherin-mediated cell-to-cell adhesion in human embryonal carcinoma cells. (2/294)
Human embryonal carcinoma (EC) cells typically require high cell densities to maintain their characteristic phenotype; they are generally subject to differentiation when cultured at low cell densities, marked by changes in morphology and expression of the surface antigen, SSEA-1. To test whether cadherin mediated cell-to-cell adhesion may be responsible for maintaining an EC phenotype we ascertained that human EC cells generally express E- and P-cadherins, and are subject to cadherin mediated, Ca2+ dependent aggregation. However, in the NTERA2 human EC cell line, inhibition of cadherin mediated adhesion by culture in low levels of Ca2+ did not result in the changes typically seen under low cell density conditions. Low Ca2+ levels also did not affect the pattern of differentiation in these cells following induction with retinoic acid. Therefore, cadherin-mediated cell adhesion does not appear to play a role in maintaining an EC phenotype. On the other hand, culture at both low cell density and in the absence of Ca2+ did result in changes in the patterns of cadherin expression suggesting a feedback regulatory effect of cell-to-cell adhesion. Further, lithium which inhibits the cytoplasmic kinase GSK3beta and hence influences beta-catenin levels did cause differentiation of NTERA2 cells. However, consideration of the phenotype of the resultant cells suggested that this effect may be because of lithium mimicking activation of a Wnt signalling pathway, rather than an effect on signalling consequent upon cadherin mediated cell to cell adhesion. (+info)Anomalous high p27/KIP1 expression in a subset of aggressive B-cell lymphomas is associated with cyclin D3 overexpression. p27/KIP1-cyclin D3 colocalization in tumor cells. (3/294)
p27 cyclin-dependent kinase inhibitor downregulation is essential for transition to the S phase of the cell cycle. Thus, proliferating cells in reactive lymphoid tissue show no detectable p27 expression. Nevertheless, anomalous high p27 expression has been shown to be present in a group of aggressive B-cell lymphomas with high proliferation index and adverse clinical outcome. This suggests that abnormally accumulated p27 protein has been rendered functionally inactive. We analyzed the causes of this anomalous presence of p27 in a group of aggressive B-cell lymphomas, including 54 cases of diffuse large B-cell lymphomas and 20 Burkitt's lymphomas. We simultaneously studied them for p27, cyclin D3, cyclin D2, cyclin D1, and cyclin E expression, because it has been stated that high levels of expression of cyclin D1 or E lead to increased p27 levels in some cell types. A statistically significant association between p27 and cyclin D3 expression was found for the group as a whole. Additionally, when dividing the cases according to the level of expression of cyclin D3 by reactive germinal centers, it was observed that cases with stronger cyclin D3 expression also show higher p27 expression. The relationship between both proteins was also shown at a subcellular level by laser confocal studies, showing that in cases with high expression of both proteins there was a marked colocalization. Additional evidence in favor of p27 sequestration by cyclin D3 was provided by coimmunoprecipitation studies in a Burkitt's cell line (Raji) showing the existence of cyclin D3/p27 complexes and the absence of CDK2/p27 complexes. These results could support the hypothesis that there are cyclin D3/p27 complexes in a subset of aggressive B-cell lymphomas in which p27 lacks the inhibitory activity found when it is bound to cyclin E/CDK2 complexes. This interaction between both proteins could lead to an abnormal nuclear accumulation, detectable by immunohistochemical techniques. (+info)A metalloprotease prepares the way. (4/294)
In the nematode Caenorhabditis elegans gonad shape and size is determined by the migration of a leader cell, which is at the tip of the growing gonad arm. A metalloprotease secreted by the leader cell has recently been found to play an essential role in this process, preparing the way ahead for the cell's migration. (+info)Hodgkin and Reed-Sternberg-like cells in B-cell chronic lymphocytic leukemia represent the outgrowth of single germinal-center B-cell-derived clones: potential precursors of Hodgkin and Reed-Sternberg cells in Hodgkin's disease. (5/294)
In rare cases of B-cell chronic lymphocytic leukemia (B-CLL), large cells morphologically similar to or indistinguishable from Hodgkin/Reed-Sternberg (HRS) cells of Hodgkin's disease (HD) can be found in a background of otherwise typical B-CLL. To test these HRS-like cells for a potential clonal relationship to the B-CLL cells, single cells were micromanipulated from immunostained tissue sections, and rearranged immunoglobulin genes were amplified from HRS-like cells and B-CLL cells and sequenced. The same variable (V) gene rearrangements with shared and distinct somatic mutations were found in HRS-like and B-CLL cells from 1 patient, which indicates derivation of these cells from 2 distinct members of a germinal-center B-cell clone. Separate clonal V gene rearrangements were amplified from HRS-like and B-CLL cells from 2 other patients, showing concomitant presence of 2 distinct expanded B-cell clones. Epstein-Barr virus (EBV) was detected in the HRS-like cells of these 2 latter cases, indicating clonal expansion of an EBV-harboring B cell in the setting of B-CLL. There is evidence that HRS-like cells in B-CLL, like HRS cells in HD, derive from germinal-center B cells. In all cases, somatic mutations have been detected in the rearranged V genes of the HRS-like cells, and in 1 of the EBV-positive HRS-like cell clones, somatic mutations rendered an originally functional V gene rearrangement nonfunctional. We speculate that the HRS-like cells in B-CLL represent potential precursors for HRS cells causing HD. (+info)Synergy of SF1 and RAR in activation of Oct-3/4 promoter. (6/294)
The Oct-3/4 transcription factor is expressed in the earliest stages of embryogenesis, and is thus likely to play an important role in regulation of initial decisions in development. For the first time, we have shown that SF1 and Oct-3/4 are co-expressed in embryonal carcinoma (EC) P19 cells, and their expression is down-regulated with very similar kinetics following retinoic acid (RA) induced differentiation of these cells, suggesting a functional relationship between the two. Previously, we have shown that the Oct-3/4 promoter harbors an RA-responsive element, RAREoct, which functions in EC cells as a binding site for positive regulators of transcription, such as RAR and RXR. In this study we have identified in the Oct-3/4 promoter two novel SF1-binding sites: SF1(a) and SF1(b). The proximal site, SF1(a), is located within the RAREoct, and the distal site, SF1(b), is located between nucleotide -193 and -209 of the Oct-3/4 promoter. Both sites contribute to activation of Oct-3/4 promoter in EC cells, with SF1(a) playing a more crucial role. SF1, and its isoforms ELP2 and ELP3 bind to both SF1 sites and activate the Oct-3/4 promoter. This activation depends on the presence of SF1 DNA-binding domain. Thus, Oct-3/4 is the first EC-specific gene reported that is regulated by SF1. Interestingly, SF1 and RAR form a novel complex on the RAREoct sequence that synergistically activate the Oct-3/4 promoter. Both RARE and SF1 cis regulatory elements, as well as the SF1 DNA-binding domain, are needed for this synergism. SF1 and Oct-3/4 transcription factors play a role in the same developmental regulatory cascade. (+info)Pleiotrophin can be rate-limiting for pancreatic cancer cell growth. (7/294)
Pancreatic cancer is one of the most aggressive malignant tumors, with an overall survival rate of 2%. The identification of growth factors that contribute to the malignant phenotype can help to identify new targets for therapy. In this study, we analyzed the growth factor pleiotrophin (PTN) that was originally described as a developmentally regulated cytokine during early embryogenesis. More recently, PTN was found to be overexpressed in a variety of neuroectodermal tumors and described as an essential angiogenic growth factor in choriocarcinoma and melanoma, promoting metastatic growth. Recently, we discovered high expression levels of PTN in patients with gastrointestinal malignancies, particularly in those patients with pancreatic cancer. However, it is not known whether PTN is a contributor to the growth of pancreatic cancer or is only a bystander. We used ribozymes to deplete PTN mRNA from Colo357 pancreatic cancer cells and studied the resulting phenotype. The reduction of PTN resulted in a decrease in the proliferation rate, soft agar colony formation, and tumor growth in animals. Supplementation of cells with PTN partially reversed the ribozyme effect. The autocrine function of PTN was confirmed by using PTN-binding antibodies that inhibited the proliferation rate by 50% in Colo357 cells but also in a different pancreatic cancer cell line, Panc89. Our study identifies PTN as a new and essential growth factor for pancreatic cancer. Due to the restricted expression pattern of PTN in adults, PTN is suggested as a target for pancreatic cancer therapy. (+info)Nodal signaling uses activin and transforming growth factor-beta receptor-regulated Smads. (8/294)
Nodal, a member of the transforming growth factor beta (TGF-beta) superfamily, is implicated in many events critical to the early vertebrate embryo, including mesoderm formation, anterior patterning, and left-right axis specification. Here we define the intracellular signaling pathway induced by recombinant nodal protein treatment of P19 embryonal carcinoma cells. Nodal signaling activates pAR3-Lux, a luciferase reporter previously shown to respond specifically to activin and TGF-beta. However, nodal is unable to induce pTlx2-Lux, a reporter specifically responsive to bone morphogenetic proteins. We also demonstrate that nodal induces p(CAGA)(12), a reporter previously shown to be specifically activated by Smad3. Expression of a dominant negative Smad2 significantly reduces the level of luciferase reporter activity induced by nodal treatment. Finally, we show that nodal signaling rapidly leads to the phosphorylation of Smad2. These results provide the first direct biochemical evidence that nodal signaling is mediated by both activin-TGF-beta pathway Smads, Smad2 and Smad3. We also show here that the extracellular cripto protein is required for nodal signaling, making it distinct from activin or TGF-beta signaling. (+info)Embryonal carcinoma stem cells (ECSCs) are a type of cancer stem cell found in embryonal carcinomas, which are a rare form of germ cell tumor that primarily affect the testicles and ovaries. These stem cells are characterized by their ability to differentiate into various cell types, similar to embryonic stem cells. They are believed to play a key role in the development and progression of embryonal carcinomas, as they can self-renew and generate the heterogeneous population of cancer cells that make up the tumor.
Embryonal carcinoma stem cells have been studied extensively as a model system for understanding the biology of cancer stem cells and developing new therapies for germ cell tumors. They are known to express specific markers, such as Oct-4, Nanog, and Sox2, which are also expressed in embryonic stem cells and are involved in maintaining their pluripotency.
It is important to note that while embryonal carcinoma stem cells share some similarities with embryonic stem cells, they are distinct from them and have undergone malignant transformation, making them a target for cancer therapy.
Embryonal carcinoma is a rare and aggressive type of cancer that arises from primitive germ cells. It typically occurs in the gonads (ovaries or testicles), but can also occur in other areas of the body such as the mediastinum, retroperitoneum, or sacrococcygeal region.
Embryonal carcinoma is called "embryonal" because the cancerous cells resemble those found in an embryo during early stages of development. These cells are capable of differentiating into various cell types, which can lead to a mix of cell types within the tumor.
Embryonal carcinoma is a highly malignant tumor that tends to grow and spread quickly. It can metastasize to other parts of the body, including the lungs, liver, brain, and bones. Treatment typically involves surgical removal of the tumor, followed by chemotherapy and/or radiation therapy to kill any remaining cancer cells.
Prognosis for embryonal carcinoma depends on several factors, including the stage of the disease at diagnosis, the location of the tumor, and the patient's overall health. In general, this type of cancer has a poor prognosis, with a high risk of recurrence even after treatment.
A teratoma is a type of germ cell tumor, which is a broad category of tumors that originate from the reproductive cells. A teratoma contains developed tissues from all three embryonic germ layers: ectoderm, mesoderm, and endoderm. This means that a teratoma can contain various types of tissue such as hair, teeth, bone, and even more complex organs like eyes, thyroid, or neural tissue.
Teratomas are usually benign (non-cancerous), but they can sometimes be malignant (cancerous) and can spread to other parts of the body. They can occur anywhere in the body, but they're most commonly found in the ovaries and testicles. When found in these areas, they are typically removed surgically.
Teratomas can also occur in other locations such as the sacrum, coccyx (tailbone), mediastinum (the area between the lungs), and pineal gland (a small gland in the brain). These types of teratomas can be more complex to treat due to their location and potential to cause damage to nearby structures.
Tretinoin is a form of vitamin A that is used in the treatment of acne vulgaris, fine wrinkles, and dark spots caused by aging or sun damage. It works by increasing the turnover of skin cells, helping to unclog pores and promote the growth of new skin cells. Tretinoin is available as a cream, gel, or liquid, and is usually applied to the affected area once a day in the evening. Common side effects include redness, dryness, and peeling of the skin. It is important to avoid sunlight and use sunscreen while using tretinoin, as it can make the skin more sensitive to the sun.
Cell differentiation is the process by which a less specialized cell, or stem cell, becomes a more specialized cell type with specific functions and structures. This process involves changes in gene expression, which are regulated by various intracellular signaling pathways and transcription factors. Differentiation results in the development of distinct cell types that make up tissues and organs in multicellular organisms. It is a crucial aspect of embryonic development, tissue repair, and maintenance of homeostasis in the body.
Neoplastic stem cells, also known as cancer stem cells (CSCs), are a subpopulation of cells within a tumor that are capable of self-renewal and generating the heterogeneous lineages of cells that comprise the tumor. These cells are believed to be responsible for the initiation, maintenance, and progression of cancer, as well as its recurrence and resistance to therapy.
CSCs share some similarities with normal stem cells, such as their ability to divide asymmetrically and give rise to differentiated progeny. However, they also have distinct characteristics that distinguish them from their normal counterparts, including aberrant gene expression, altered signaling pathways, and increased resistance to apoptosis (programmed cell death).
The existence of CSCs has important implications for cancer diagnosis, treatment, and prevention. Targeting these cells specifically may be necessary to achieve durable remissions and prevent relapse, as they are thought to survive conventional therapies that target the bulk of the tumor. Further research is needed to better understand the biology of CSCs and develop effective strategies for their elimination.
According to the National Institutes of Health (NIH), stem cells are "initial cells" or "precursor cells" that have the ability to differentiate into many different cell types in the body. They can also divide without limit to replenish other cells for as long as the person or animal is still alive.
There are two main types of stem cells: embryonic stem cells, which come from human embryos, and adult stem cells, which are found in various tissues throughout the body. Embryonic stem cells have the ability to differentiate into all cell types in the body, while adult stem cells have more limited differentiation potential.
Stem cells play an essential role in the development and repair of various tissues and organs in the body. They are currently being studied for their potential use in the treatment of a wide range of diseases and conditions, including cancer, diabetes, heart disease, and neurological disorders. However, more research is needed to fully understand the properties and capabilities of these cells before they can be used safely and effectively in clinical settings.
Carcinoma is a type of cancer that develops from epithelial cells, which are the cells that line the inner and outer surfaces of the body. These cells cover organs, glands, and other structures within the body. Carcinomas can occur in various parts of the body, including the skin, lungs, breasts, prostate, colon, and pancreas. They are often characterized by the uncontrolled growth and division of abnormal cells that can invade surrounding tissues and spread to other parts of the body through a process called metastasis. Carcinomas can be further classified based on their appearance under a microscope, such as adenocarcinoma, squamous cell carcinoma, and basal cell carcinoma.
Embryonic stem cells are a type of pluripotent stem cell that are derived from the inner cell mass of a blastocyst, which is a very early-stage embryo. These cells have the ability to differentiate into any cell type in the body, making them a promising area of research for regenerative medicine and the study of human development and disease. Embryonic stem cells are typically obtained from surplus embryos created during in vitro fertilization (IVF) procedures, with the consent of the donors. The use of embryonic stem cells is a controversial issue due to ethical concerns surrounding the destruction of human embryos.
Hematopoietic stem cells (HSCs) are immature, self-renewing cells that give rise to all the mature blood and immune cells in the body. They are capable of both producing more hematopoietic stem cells (self-renewal) and differentiating into early progenitor cells that eventually develop into red blood cells, white blood cells, and platelets. HSCs are found in the bone marrow, umbilical cord blood, and peripheral blood. They have the ability to repair damaged tissues and offer significant therapeutic potential for treating various diseases, including hematological disorders, genetic diseases, and cancer.
Stem cell transplantation is a medical procedure where stem cells, which are immature and unspecialized cells with the ability to differentiate into various specialized cell types, are introduced into a patient. The main purpose of this procedure is to restore the function of damaged or destroyed tissues or organs, particularly in conditions that affect the blood and immune systems, such as leukemia, lymphoma, aplastic anemia, and inherited metabolic disorders.
There are two primary types of stem cell transplantation: autologous and allogeneic. In autologous transplantation, the patient's own stem cells are collected, stored, and then reinfused back into their body after high-dose chemotherapy or radiation therapy to destroy the diseased cells. In allogeneic transplantation, stem cells are obtained from a donor (related or unrelated) whose human leukocyte antigen (HLA) type closely matches that of the recipient.
The process involves several steps: first, the patient undergoes conditioning therapy to suppress their immune system and make space for the new stem cells. Then, the harvested stem cells are infused into the patient's bloodstream, where they migrate to the bone marrow and begin to differentiate and produce new blood cells. This procedure requires close monitoring and supportive care to manage potential complications such as infections, graft-versus-host disease, and organ damage.
Pluripotent stem cells are a type of undifferentiated stem cell that have the ability to differentiate into any cell type of the three germ layers (endoderm, mesoderm, and ectoderm) of a developing embryo. These cells can give rise to all the cell types that make up the human body, with the exception of those that form the extra-embryonic tissues such as the placenta.
Pluripotent stem cells are characterized by their ability to self-renew, which means they can divide and produce more pluripotent stem cells, and differentiate, which means they can give rise to specialized cell types with specific functions. Pluripotent stem cells can be derived from embryos at the blastocyst stage of development or generated in the lab through a process called induced pluripotency, where adult cells are reprogrammed to have the properties of embryonic stem cells.
Pluripotent stem cells hold great promise for regenerative medicine and tissue engineering because they can be used to generate large numbers of specific cell types that can potentially replace or repair damaged or diseased tissues in the body. However, their use is still a subject of ethical debate due to concerns about the source of embryonic stem cells and the potential risks associated with their use in clinical applications.
A cell line that is derived from tumor cells and has been adapted to grow in culture. These cell lines are often used in research to study the characteristics of cancer cells, including their growth patterns, genetic changes, and responses to various treatments. They can be established from many different types of tumors, such as carcinomas, sarcomas, and leukemias. Once established, these cell lines can be grown and maintained indefinitely in the laboratory, allowing researchers to conduct experiments and studies that would not be feasible using primary tumor cells. It is important to note that tumor cell lines may not always accurately represent the behavior of the original tumor, as they can undergo genetic changes during their time in culture.
Adult stem cells, also known as somatic stem cells, are undifferentiated cells found in specialized tissues or organs throughout the body of a developed organism. Unlike embryonic stem cells, which are derived from blastocysts and have the ability to differentiate into any cell type in the body (pluripotency), adult stem cells are typically more limited in their differentiation potential, meaning they can only give rise to specific types of cells within the tissue or organ where they reside.
Adult stem cells serve to maintain and repair tissues by replenishing dying or damaged cells. They can divide and self-renew over time, producing one daughter cell that remains a stem cell and another that differentiates into a mature, functional cell type. The most well-known adult stem cells are hematopoietic stem cells, which give rise to all types of blood cells, and mesenchymal stem cells, which can differentiate into various connective tissue cells such as bone, cartilage, fat, and muscle.
The potential therapeutic use of adult stem cells has been explored in various medical fields, including regenerative medicine and cancer therapy. However, their limited differentiation capacity and the challenges associated with isolating and expanding them in culture have hindered their widespread application. Recent advances in stem cell research, such as the development of techniques to reprogram adult cells into induced pluripotent stem cells (iPSCs), have opened new avenues for studying and harnessing the therapeutic potential of these cells.
Squamous cell carcinoma is a type of skin cancer that begins in the squamous cells, which are flat, thin cells that form the outer layer of the skin (epidermis). It commonly occurs on sun-exposed areas such as the face, ears, lips, and backs of the hands. Squamous cell carcinoma can also develop in other areas of the body including the mouth, lungs, and cervix.
This type of cancer usually develops slowly and may appear as a rough or scaly patch of skin, a red, firm nodule, or a sore or ulcer that doesn't heal. While squamous cell carcinoma is not as aggressive as some other types of cancer, it can metastasize (spread) to other parts of the body if left untreated, making early detection and treatment important.
Risk factors for developing squamous cell carcinoma include prolonged exposure to ultraviolet (UV) radiation from the sun or tanning beds, fair skin, a history of sunburns, a weakened immune system, and older age. Prevention measures include protecting your skin from the sun by wearing protective clothing, using a broad-spectrum sunscreen with an SPF of at least 30, avoiding tanning beds, and getting regular skin examinations.
Hepatocellular carcinoma (HCC) is the most common type of primary liver cancer in adults. It originates from the hepatocytes, which are the main functional cells of the liver. This type of cancer is often associated with chronic liver diseases such as cirrhosis caused by hepatitis B or C virus infection, alcohol abuse, non-alcoholic fatty liver disease (NAFLD), and aflatoxin exposure.
The symptoms of HCC can vary but may include unexplained weight loss, lack of appetite, abdominal pain or swelling, jaundice, and fatigue. The diagnosis of HCC typically involves imaging tests such as ultrasound, CT scan, or MRI, as well as blood tests to measure alpha-fetoprotein (AFP) levels. Treatment options for Hepatocellular carcinoma depend on the stage and extent of the cancer, as well as the patient's overall health and liver function. Treatment options may include surgery, radiation therapy, chemotherapy, targeted therapy, or liver transplantation.