Cancer Stem Cells: Properties, Concepts and Models

Cancer Stem Cells: Properties, Concepts and Models Tumours are made up of a heterogeneous population of cells which are distinct in terms of their differentiation competencies, proliferative capabilities as well as functional properties. [A] The mechanisms responsible for such heterogeneity are the subject of research, and two models have been put forth in order to explain the phenomenon – Cancer stem cells (CSCs) and clonal evolution. [A] Cancer stem cells are a subset of the total population of cells in a tumour that have the ability to undergo self-renewal, as well as to differentiate into the different types of cells that comprise the tumour. [A] These CSCs are said to be responsible for tumorigenesis as well as for driving tumour growth. [U] Evidence supporting the existence of cancer stem cells Differences in clonogenicity among cancer cells were first documented in cases of leukaemia and multiple myeloma. It was found that 0.01 – 1% of the cells were capable of extensive proliferation, and able to establish colonies when grown in vitro (Park, C. H., Bergsagel, D. E. McCulloch, E. A. Mouse myeloma tumor stem cells: a primary cell culture assay. J. Natl Cancer Inst. 46, 411–422 (1971). Two possible explanations existed for this – either leukemic cells had a low overall capacity for proliferation, or only a definite subset of these cells were clonogenic. In 1994, John Dick and his group of researchers carried out a landmark study where CSCs were isolated from a mouse model that had been transplanted with human AML cells. [Z15] This was the first conclusive evidence for the existence of a subset of the leukaemia cells that were highly clonogenic, in comparison to the remaining cancer cells. It was later observed that a similar condition exists in the case of solid tumours, where only a small subset of the total cell population is tumorigenic. [G] Origins of cancer stem cells Several contradictory theories exist regarding the cellular origins of cancer stem cells. Some state that these cells are derived from normal stem cells that have acquired oncogenic mutations [G], others refute this with the claim that cancer stem cells can arise from a committed progenitor cell that has acquired the properties of a stem-cell during its cancerous transformation [Z1], while yet others suggest that these cells could arise as a result of a fusion event between a stem cell and a tumour cell. [N] The idea that cancers could arise from normal stem cells is highly plausible because not only do they continuously undergo divisions, but they are also long lived, allowing them to accumulate multiple mutations, as is required for a cancerous transformation. [B] Apart from the accumulation of mutations, the interaction of a cell with its local microenvironment also influences the tumorigenic process. Mouse leukaemia models have been able to provide evidence that given suitable niche conditions, a progenitor cell is capable of de-differentiating to form a CSC. [V] However, since most progenitor and mature cells have a relatively short life-span, it seems unlikely that will be able to acquire the oncogenic mutations required to render them tumorigenic. [I] Despite these explanations, the exact origin of most tumours and cancer stem cells remains unknown, and can only be speculated based on experimental findings. [A] Additionally, irrespective of the origin, the identification and isolation of CSCs in a tumour indicates that there exists a functional hierarchy exists within the tumour tissue. [L] Properties of cancer stem cells These cells can undergo symmetric as well as asymmetric divisions, which results in the expansion of the cancer stem cell population itself, as well as an increase in the number of differentiated cells that constitute the bulk of the tumour. [Z1] THE CANCER STEM CELL MODEL As previously mentioned, two models have been put forth to explain the heterogeneity of a tumour cell population. The first model is the CSC model, also known as the hierarchical model, which states that within a tumour, there exist different classes of cells and that the CSCs represent a biologically distinct subpopulation of cells that are capable of propagating the tumour. [C] It suggests that the characteristics of the cells within the tumour are intrinsically determined and therefore only certain cells possess the ability to undergo extensive proliferation to initiate tumour formation, these cells are called the CSCs; while the remaining cells are incapable of tumorigenisis. According to the CSC model, although most cancers arise from a group of cells that are genetically monoclonal in nature, the high level of tumour heterogeneity is a result of the interaction between cells that are in different states of differentiation after have initiated from a common precursor. [Z12] Evidence supporting this hypothesis emerges from the observation that though tumours may initially respond well to chemotherapy, there is often a case of relapse; which could occur due to the CSCs that persist post-treatment and are then able to re-initiate tumour formation. [Z13] There are, however, limitations to the CSC model; the first being that all studies that support it have only addressed the potential of the cells to proliferate and give rise to tumours, but not the actual fate. [D] Since the conditions applied to test the tumorigenic potential of these cells may vary considerably from the conditions experienced by the cells in vivo, we do not know which of these cells actually contribute to the establishment and growth of the primary tumour. It is also noteworthy that it has been found that if the population of cancer cells acquires an immense number of mutations and aberrations, then almost all of them begin to show stem-like properties. [C] In such a case, the CSC model becomes irrelevant. On the other hand, the stochastic model states that cells in a tumour are biologically equivalent, and that each cell has the ability to act as a CSC, given the right circumstances. A combination of intrinsic and extrinsic influences is said to determine the proliferative capacity and the ultimate fate of a cell. [C] Behaviour of a cell is therefore not pre-determined by intrinsic characters alone and tumour initiating cells cannot be enriched. It is however likely for both these paradigms to be observed in vivo, in different cancers. Some cancers may follow the CSC model, while others may not. Based on transplantation studies in mice, it has been found that only in a fraction of cases, does AML follow the CSC model while in others there is no evidence for the existence of a highly tumorigenic sub-population of cells that continue to display CSC activity upon serial propagation. [F] Therefore, although CSCs may be responsible for driving the growth of a majority of tumours and cancers, there are studies which indicate that certain malignancies may be sustained primarily by the bulk of the tumour cells. [F] IDENTIFICATION AND ISOLATION OF CANCER STEM CELLS Cancer stem cell assays Purification and enrichment techniques CSC markers CSCs in various cancers HETEROGENEITY IN CANCER STEM CELL POPULATIONS Based on the study of the CSC model, the question arises as to whether similar hierarchical subpopulations of tumorigenic and non-tumorigenic are observed in patients suffering from the same type of cancer; and whether these tumorigenic CSCs can be isolated based on conserved cell- surface markers. However it has been found that there are often phenotypic differences in CSCs even within the same cancer sub-type. [E] For example, though it has been found that the CD44+/CD24- population of breast cancer cells are generally tumorigenic, this is not universally the case and in certain cases, it has been found that cells of diverse phenotypes are able to act as CSCs. (Al-Hajj, M., Wicha, M.S., Benito-Hernandez, A., Morrison, S.J., and Clarke, M.F. (2003). Proc. Natl. Acad. Sci. USA 100, 3983–3988.) Similarly, in gliomas CD133 expression is not always associated with CSCs, and in certain instances CD133- cells have also been found to be tumorigenic. (Beier, D. et al. CD133+ and CD133– glioblastoma derived cancer stem cells show differential growth characteristics and molecular profiles. Cancer Res. 67, 4010–4015 (2007). Apart from the phenotype, the frequency of CSCs in a solid tumour or population of cancer cells is also variable. In melanomas, CSCs constitute anything between 1.6 to 20% of the total cells, while in the case of colorectal carcinomas, they represent between 1.8 to 24.5% of the cells. [A] Additionally, in general, the percentage of CSCs in solid tumours has been found to be significantly higher than the percentage of leukemic stem cells. [Z15] This heterogeneity has implications on the prognosis of the disease as well as the outcomes of various therapeutic interventions. It is envisioned that with the identification of more refined markers and improved methods for determination of CSC frequency, we may eventually be able to correlate the percentage of CSCs with the tumour grade and the outcome. [A]

Wildes Importance of Being Earnest and Weschlers Boggs Essay

Wilde's "Importance of Being Earnest" and Weschler's "Boggs" At first glance, Oscar Wilde’s The Importance of Being Earnest and Lawrence Weschler’s Boggs: A Comedy of Values treat the issue of art’s function in converse ways. Wilde, the quintessential Aesthete, asserts that art should exist for the sake of beauty alone. Boggs, on the other hand, contends that art should serve a practical function: it should wake individuals from their sleepwalking by highlighting essential, overlooked aspects of society. Fascinatingly, neither Wilde nor Boggs firmly adheres to his ostensible artistic purpose. Wilde’s Importance of Being Earnest, although it showcases certain Aesthetic elements, incisively critiques Victorian society. The play is not a functionless work of pure beauty. Conversely, Boggs’ project clearly serves an instructional function while it simultaneously revels in its own beauty. Moreover, Boggs himself is often uncertain of what his art represents and does. When placed side-by-side, The Importanc e of Being Earnest and Boggs queer the division between Aestheticism and Functionalism, suggesting that both schools are unattainable ideals. In doing so, the two texts elucidate a holistic conception of art that fuses aesthetic value to social critique. Aesthetic beauty coalesces with function. Historically, Wilde was a staunch—even notorious—advocate of Aestheticism: a doctrine popular throughout Europe in the late nineteenth century which held that â€Å"art exists for the sake of its beauty alone, and that it need serve no political, didactic, or other purpose† (Britannica). Indeed, David Cooper in his Companion to Aesthetics argues that the doctrine â€Å"asserts not merely that a work of art should be judged only on ... ... [pleasure, beauty]† (GP 799) were most valued in the fourteenth century, and as we have seen, they still are today. Art must be beautiful and purposefully inspire thought. Works Cited "Aestheticism." Encyclopà ¦dia Britannica. 2005. Encyclopà ¦dia Britannica Online. 30 Nov. 2005 . Chaucer, Geoffrey. The Riverside Chaucer. Ed. Larry D. Benson. 3rd ed. Boston: Houghton, 1987. Cooper, David, ed. A Companion to Aesthetics. Oxford: Blackwell, 1995. Foster, Richard. â€Å"Wilde as Parodist: A Second Look at The Importance of Being Earnest.† College English 18.1 (1956): 18-23. â€Å"Functionalism.† American Heritage Dictionary of the English Language, 4th ed. 2000. Weschler, Lawrence. Boggs: A Comedy of Values. Chicago: Chicago UP, 1987. Wilde, Oscar. The Importance of Being Earnest and Other Plays. Ed. Richard Allen Cave. New York: Penguin, 2000.

What is an Art?

In her article â€Å"A Shark in the Mind of One Contemplating Wilderness†, Terry Tempest Williams effectively defines what an â€Å"art† is and what is not. It goes beyond its traditional definition as a product of human creativity in which materials are outlined and selected to convey visually interesting forms. Williams reveals the ongoing battle within the biodiversity – human versus nature – and equates human life to the characters in the wild to create a vivid description of Art. Like a shark suspended in formaldehyde and being viewed as a unique work of art, Williams sees the same scenario for human beings when nature is totally devastated. Who’s to blame? The increased level of extinction that is likely to lead to the disappearance of about two-thirds of all kinds of living organisms by the end of the next century is driven by only one species: human (Raven 4). Human is inseparable from nature. His survival depends inextricably on other life forms. Life is the common force that connects man to animals. Williams recognizes this connection through an encounter with a shark in a tank, â€Å"I press my hands on the glass, waiting for the shark to pass by again, and when it does I feel my own heart beating against the mind of this creature that kills. However, this bond is unfastened little by little by man’s activities that are detrimental to the nature. Civilization overwhelms man that he neglects the reality that his existence rests on the subsistence of the natural world. Rather than protecting his source of life, he becomes the author of its destruction. Logging and mining, whether legal or illegal, are two of the most common damaging human activities. For pharmaceutical companies, â€Å"Wilderness is a cabinet of pharmaceuticals waiting to be discovered. † Taking her own experience where an open space once used by children to lie on their backs was now converted to a food court, Williams realized how fast people can transform something into another thing. Quoting her observation, â€Å"What was never before seen as art, as dance, as a painting in motion, but imagined only through the calculations of biologists, their facts now metamorphosed into designs†¦. † Just imagine how man has gotten so much from the nature and exploited a very huge part of it. As Williams noted, â€Å"The natural world is becoming invisible, appearing only as a backdrop for our own human dramas and catastrophes. Landslides, flashfloods, earthquakes, and tornadoes are signs that nature is too much burdened of man’s destructive activities. Wilderness is a work of art. People shape this natural wasteland just like how an artist makes a mosaic. The development of agricultural lands into subdivisions, the burning of forests to produce industrial m aterials, and even the changing color of water in the rivers from blue to black, reflect how an artist designs and colors his work. â€Å"What is true for wilderness remains true for humans. Human society is the mosaic of field and forest, of city blocks, of subway tiles. It is to this mosaic that we should turn in order to understand what it really means to be human† (Amato-Grill 5). Like humans, other forms of life need a habitat where they can build their own community. â€Å"We are animals, in search of a home, in relationship to Other, an expanding community with a mosaic of habitats, domestic and wild,† Williams explained. In the same way that we have seen performances on stage, we have set our eyes on how the leaves of the trees dance in the wind, how animals hide and catch their prey, how whales and fishes create waves in the oceans, and how flowers patiently wait for its bud to bloom. Wilderness, according to Williams, is a grand piece of performance art that can embody or inspire. To preserve them is to let the next generation witness the grand performance arts of nature. The nature is a work of art itself creatively designed and created by its Artist. It is a spring of inspiration for the artists who are also masterpieces of the One who created the nature. Art, as implicitly described by Williams on her article, is the exploration yet preservation of these natural creations.

Group dynamics The Breakfast Club Essay - 1055 Words

Whether groups are formed for social or task oriented purposes, the ability to produce and maintain a sense of affiliation, peer support and collaboration is important for overall group functioning. The cohesion of a social group is produced through the establishment of a set of group norms, which are later defined as a guide for conduct accepted within a group of individuals. However, in order for a group to perform and produce results, the team leader should guide his/her team through the proper stages of group development, which includes the following steps: forming, storming, norming, performing and adjourning. Although teams should follow all these stages of group development, the forming and the norming stages are the most important,†¦show more content†¦At this stage, the group begins to realize the more positive points of individuals within the group, which promotes the development of trust and respect which begins to build group cohesion. The next stage is the perf orming stage, which is typical of high-performing teams that are able to function as a group and figure out various options to get the job done smoothly and effectively without supervision. The final stage is the adjourning phase, which is the final step in completing tasks and breaking up the team. The groups that are formed as adolescents often determine group associations as adults and define an individual within their social group that will either set them with or against other groups. This is described in an article on social groupings by Colin Allen, which mentions that our social associations as adolescents are strong indicators to future patterns of social norms as adults. Therefore, the group of students in the movie, The Breakfast Club, can also be extrapolated to adult group dynamics. However, the varying social norms between groups can present conflicts when adults are required to function within a very diverse group of individuals. In The Breakfast Club, the Jock, Geek, Prom Queen, Delinquent, and the Freak groups are brought together initially through an autocratic or directive leadership role, used to bring the group together in order to proceed to the next phase of group development. This stage is particularly important within a group ofShow MoreRelatedThe Breakf ast Club Essay1071 Words   |  5 Pagesâ€Å"The Breakfast Club† is a film that is well-know to be a movie that explains stereotypes and societal standards. This classic movie exemplifies group dynamic in society. It does this by portraying distinct stereotypes, varying from the so-called â€Å"princess† all the way to the so-called â€Å"criminal.† At the start of the film, each member in the group is completely different and separate. They were definitely considered an out-group, which is a group of people that don’t identify with one another. 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