1,721,226 research outputs found
Evolution of cooperation among tumor cells
No full textThe evolution of cooperation has a well established theoretical framework based on game theory. This approach has made valuable contributions to a wide variety of disciplines, including political science, economics, and evolutionary biology. Existing cancer theory suggests that individual clones of cancer cells evolve independently from one another, acquiring all of the genetic traits or hallmarks necessary to form a malignant tumor. It is also now recognized that tumors are heterotypic, with cancer cells interacting with normal stromal cells within the issue microenvironment, including endothelial, stromal, and nerve cells. This tumor cell???stromal cell interaction in itself is a form of commensalism, because it has been demonstrated that these nonmalignant cells support and even enable tumor growth. Here, we add to this theory by regarding tumor cells as game players whose interactions help to determine their Darwinian fitness. We marshal evidence that tumor cells overcome certain host defenses by means of diffusible products. Our original contribution is to raise the possibility that two nearby cells can protect each other from a set of host defenses that neither could survive alone. Cooperation can evolve as byproduct mutualism among genetically diverse tumor cells. Our hypothesis supplements, but does not supplant, the traditional view of carcinogenesis in which one clonal population of cells develops all of the necessary genetic traits independently to form a tumor. Cooperation through the sharing of diffusible products raises new questions about tumorigenesis and has implications for understanding observed phenomena, designing new experiments, and developing new therapeutic approaches.Author manuscript. Published in final edited form as: Proc Natl Acad Sci U S A. 2006 September 5; 103(36): 13474-13479.The final published version of this article is located at: www.pnas.org/cgi/doi/10.1073/pnas.0606053103NIH U56 CA113004; to David E. AxelrodR.A. was supported by National Science Foundation (NSF) Grant SES-0240852. D.E.A. was supported by NSF Grant IIS-0312953, National Institutes of Health (NIH) Grant U56 CA113004, and New Jersey Commission on Cancer Research Grant 1076-CCR-SO. K.J.P. is an American Cancer Society Clinical Research Professor and is supported by NIH Grants CA69568, CA102872, and CA093900.NIH CA69568; to Kenneth J. PientaNIH CA102872; to Kenneth J. PientaNIH CA093900; to Kenneth J. PientaNSF SES-0240852; to Robert AxelrodNJ Commission on Cancer Research 1076-CCR-SO; to David E. AxelrodAlso available in PubMed Central. PMCID: PMC155738
Ecological therapy for cancer: Defining tumors utilizing an ecosystem paradigm suggests new opportunities for novel cancer treatments
No full textWe propose that there is an opportunity to devise new cancer therapies based on the recognition that tumors have properties of ecological systems. Traditionally, localized treatment has targeted the cancer cells directly by removing them (surgery) or killing them (chemotherapy and radiation). These modes of therapy have not always been effective because many tumors recur after these therapies, either because not all of the cells are killed (local recurrence) or because the cancer cells had already escaped the primary tumor environment (distant recurrence). There has been an increasing recognition that the tumor microenvironment contains host noncancer cells in addition to cancer cells, interacting in a dynamic fashion over time. The cancer cells compete and/or cooperate with nontumor cells, and the cancer cells may compete and/or cooperate with each other. It has been demonstrated that these interactions can alter the genotype and phenotype of the host cells as well as the cancer cells. The interaction of these cancer and host cells to remodel the normal host organ microenvironment may best be conceptualized as an evolving ecosystem. In classic terms, an ecosystem describes the physical and biological components of an environment in relation to each other as a unit. Here, we review some properties of tumor microenvironments and ecological systems and indicate similarities between them. We propose that describing tumors as ecological systems defines new opportunities for novel cancer therapies and use the development of prostate cancer metastases as an example.We refer to this as “ecological therapy” for cancer
Succesful separation between benign prostatic hyperplasia and prostate cancer by measurement of free and complexed PSA
No full textProstate-specific antigen (PSA) is a serine protease belonging to the human glandular kallikrein gene family [1–3]. The expression of PSA is mainly androgen dependent, and the detection of very high expression levels is restricted to the prostate tissue, but extraprostatic production at much lower levels has been demonstrated in several other tissues such as normal and malignant breast epithelium, endometrium, and bulbourethral glands [4–10]. PSA is synthesized by the columnar epithelium in the glandular ducts and acini of the prostate, but not by any other cells in prostate tissue. It is secreted at high concentrations (0.2-5mg/mL) into seminal fluid [4–6,11]. PSA is synthesized as an inactive precursor [2,3,12]. Like other glandular kallikreins, the PSA-precursor is processed stepwise by release of a leader peptide followed by liberation of an activation peptide that results in conversion of the zymogen into enzymatically active PSA [12]. This process may occur in parallel with the secretory release from the prostate epithelium and most probably occurs prior to the ejaculatory mixing of secretions from the prostate, seminal vesicles, and epididymis, since PSA is active in ejaculates collected from subjects with defective seminal vesicles and deferent ducts [1]. The protease(s) responsible for processing of the PSA precursor have not been identified. The mature 237-amino-acid form of PSA is a single-chain serine protease with extensive structural similarity to the glandular kallikreins [1,12–14]. However, the substrate specificity is uniquely different from that of the trypsin-like glandular kallikreins and resembles that of chymotrypsin, since PSA catalyzes the hydrolysis of peptide bonds’ carboxy-terminal to residues of tyrosine and leucine [15–17]. Synthetic peptide substrates for chymotrypsin can be used to measure PSA activity, but they are hydrolyzed much less efficiently by PSA than by chymotrypsin and are therefore both nonspecific and insensitive in detecting PSA activity [16]
Going Beyond Counting First Authors in Author Co-citation Analysis
Get PDFThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Investigations of How Cancer Cells Respond to Stress
Get PDFMetastatic cancer is incurable and causes millions of deaths each year. Cancer cells can evade stressful conditions such as hypoxia and chemotherapy exposure through various mechanisms. These stressful conditions that cancer cells are exposed to cause an increase in their already elevated reactive oxygen species (ROS) levels. In turn, the DNA damage response (DDR) of cancer cells becomes activated and arrestation of cell growth in the canonical mammalian cell cycle may occur. If the arrested cells have exited the cell cycle after S phase but before mitotic division, they can overcome exposure to chemotherapy as cancer cells in the poly-aneuploid cancer cell (PACC) state. Cancer cells in the PACC state are protected from further DNA damage and from undergoing programmed cell death. They can later undergo depolyploidization and repopulate a tumor cell population with chemotherapy-resistant progeny. Cancer cells in the PACC state are physically larger than the parental cancer cells that they arise from and undergo endocycling, causing their genomic content to be greater than these parental cancer cells as well; these two characteristics of the PACC state can be predicted to require the support of microtubules. Given the role of ROS, DDR and potentially, microtubules, in the PACC state, I decided to investigate these aspects of cancer cells of the PACC state. I studied BRCC3, CAT and SOD1 gene expression through RT-qPCR, and investigated microtubules through IF staining of -tubulin, in untreated cancer cells and cancer cells in the PACC state at various time points post-chemotherapy treatment. The results of these experiments did not show significant differences in gene expression of BRCC3, CAT or SOD1, nor in the average ⍺-tubulin quantities, between parental untreated cells and cancer cells in the PACC state post-treatment. However, the quantity of ⍺-tubulin present surrounding the perinuclear space was greater in cancer cells in the PACC state 10 days post-treatment, compared to all other cells. Due to heterogeneity within and between biological replicates in each of these experiments, further studies are needed to define the roles of ROS, DDR and microtubules in the response of cancer cells to stress, through the PACC state
Investigations of How Cancer Cells Respond to Stress
Get PDFMetastatic cancer is incurable and causes millions of deaths each year. Cancer cells can evade stressful conditions such as hypoxia and chemotherapy exposure through various mechanisms. These stressful conditions that cancer cells are exposed to cause an increase in their already elevated reactive oxygen species (ROS) levels. In turn, the DNA damage response (DDR) of cancer cells becomes activated and arrestation of cell growth in the canonical mammalian cell cycle may occur. If the arrested cells have exited the cell cycle after S phase but before mitotic division, they can overcome exposure to chemotherapy as cancer cells in the poly-aneuploid cancer cell (PACC) state. Cancer cells in the PACC state are protected from further DNA damage and from undergoing programmed cell death. They can later undergo depolyploidization and repopulate a tumor cell population with chemotherapy-resistant progeny. Cancer cells in the PACC state are physically larger than the parental cancer cells that they arise from and undergo endocycling, causing their genomic content to be greater than these parental cancer cells as well; these two characteristics of the PACC state can be predicted to require the support of microtubules. Given the role of ROS, DDR and potentially, microtubules, in the PACC state, I decided to investigate these aspects of cancer cells of the PACC state. I studied BRCC3, CAT and SOD1 gene expression through RT-qPCR, and investigated microtubules through IF staining of -tubulin, in untreated cancer cells and cancer cells in the PACC state at various time points post-chemotherapy treatment. The results of these experiments did not show significant differences in gene expression of BRCC3, CAT or SOD1, nor in the average ⍺-tubulin quantities, between parental untreated cells and cancer cells in the PACC state post-treatment. However, the quantity of ⍺-tubulin present surrounding the perinuclear space was greater in cancer cells in the PACC state 10 days post-treatment, compared to all other cells. Due to heterogeneity within and between biological replicates in each of these experiments, further studies are needed to define the roles of ROS, DDR and microtubules in the response of cancer cells to stress, through the PACC state
Variations on the Author
Get PDF“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
Appropriate Similarity Measures for Author Cocitation Analysis
Get PDFWe provide a number of new insights into the methodological discussion about author cocitation analysis. We first argue that the use of the Pearson correlation for measuring the similarity between authors’ cocitation profiles is not very satisfactory. We then discuss what kind of similarity measures may be used as an alternative to the Pearson correlation. We consider three similarity measures in particular. One is the well-known cosine. The other two similarity measures have not been used before in the bibliometric literature. Finally, we show by means of an example that our findings have a high practical relevance.information science;Pearson correlation;cosine;similarity measure;author cocitation analysis
Dispelling the Myths Behind First-author Citation Counts
Get PDFWe conducted a full-scale evaluative citation analysis study of scholars in the XML research field to explore just how different from each other author rankings resulting from different citation counting methods actually are, and to demonstrate the capability of emerging data and tools on the Web in supporting more realistic citation counting methods. Our results contest some common arguments for the continued
use of first-author citation counts in the evaluation of scholars, such as high correlations between author rankings by first-author citation counts and other citation
counting methods, and high costs of using more realistic citation counting methods that are not well-supported by the ISI databases. It is argued that increasingly available digital full text research papers make it possible for citation analysis studies to go beyond what the ISI databases have directly supported and to employ more
sophisticated methods
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