WorldWideScience

Sample records for cancer cell biology

  1. Prostate cancer stem cell biology

    OpenAIRE

    Yu, Chunyan; Yao, Zhi; Jiang, Yuan; Keller, Evan T.

    2012-01-01

    The cancer stem cell (CSC) model provides insights into pathophysiology of cancers and their therapeutic response. The CSC model has been both controversial, yet provides a foundation to explore cancer biology. In this review, we provide an overview of CSC concepts, biology and potential therapeutic avenues. We then focus on prostate CSC including (1) their purported origin as either basal-derived or luminal-derived cells; (2) markers used for prostate CSC identification; (3) alterations of s...

  2. The biology of cancer stem cells.

    Science.gov (United States)

    Lobo, Neethan A; Shimono, Yohei; Qian, Dalong; Clarke, Michael F

    2007-01-01

    Cancers originally develop from normal cells that gain the ability to proliferate aberrantly and eventually turn malignant. These cancerous cells then grow clonally into tumors and eventually have the potential to metastasize. A central question in cancer biology is, which cells can be transformed to form tumors? Recent studies elucidated the presence of cancer stem cells that have the exclusive ability to regenerate tumors. These cancer stem cells share many characteristics with normal stem cells, including self-renewal and differentiation. With the growing evidence that cancer stem cells exist in a wide array of tumors, it is becoming increasingly important to understand the molecular mechanisms that regulate self-renewal and differentiation because corruption of genes involved in these pathways likely participates in tumor growth. This new paradigm of oncogenesis has been validated in a growing list of tumors. Studies of normal and cancer stem cells from the same tissue have shed light on the ontogeny of tumors. That signaling pathways such as Bmi1 and Wnt have similar effects in normal and cancer stem cell self-renewal suggests that common molecular pathways regulate both populations. Understanding the biology of cancer stem cells will contribute to the identification of molecular targets important for future therapies. PMID:17645413

  3. Wnt Signaling in Cancer Stem Cell Biology

    Science.gov (United States)

    de Sousa e Melo, Felipe; Vermeulen, Louis

    2016-01-01

    Aberrant regulation of Wnt signaling is a common theme seen across many tumor types. Decades of research have unraveled the epigenetic and genetic alterations that result in elevated Wnt pathway activity. More recently, it has become apparent that Wnt signaling levels identify stem-like tumor cells that are responsible for fueling tumor growth. As therapeutic targeting of these tumor stem cells is an intense area of investigation, a concise understanding on how Wnt activity relates to cancer stem cell traits is needed. This review attempts at summarizing the intricacies between Wnt signaling and cancer stem cell biology with a special emphasis on colorectal cancer. PMID:27355964

  4. Human Cancer Classification: A Systems Biology- Based Model Integrating Morphology, Cancer Stem Cells, Proteomics, and Genomics

    OpenAIRE

    Halliday A Idikio

    2011-01-01

    Human cancer classification is currently based on the idea of cell of origin, light and electron microscopic attributes of the cancer. What is not yet integrated into cancer classification are the functional attributes of these cancer cells. Recent innovative techniques in biology have provided a wealth of information on the genomic, transcriptomic and proteomic changes in cancer cells. The emergence of the concept of cancer stem cells needs to be included in a classification model to capture...

  5. Inflammatory mediators: Parallels between cancer biology and stem cell therapy

    OpenAIRE

    Patel, Shyam A; Heinrich, Andrew C; Bobby Y. Reddy; Rameshwar, Pranela

    2009-01-01

    Inflammation encompasses diverse molecular pathways, and it is intertwined with a wide array of biological processes. Recently, there has been an upsurge of interest in the interactions between mediators of inflammation and other cells such as stem cells and cancer cells. Since tissue injuries are associated with the release of inflammatory mediators, it would be difficult to address this subject without considering the implications of their systemic effects. In this review, we discuss the ef...

  6. Inflammatory mediators: Parallels between cancer biology and stem cell therapy

    Directory of Open Access Journals (Sweden)

    A Patel

    2009-02-01

    Full Text Available Shyam A Patel1,2,3, Andrew C Heinrich2,3, Bobby Y Reddy2, Pranela Rameshwar21Graduate School of Biomedical Sciences, University of Medicine and Dentistry of New Jersey, Newark, NJ, USA; 2Department of Medicine – Division of Hematology/Oncology, New Jersey Medical School, University of Medicine and Dentistry of New Jersey, Newark, NJ, USA; 3These authors contributed equally to this workAbstract: Inflammation encompasses diverse molecular pathways, and it is intertwined with a wide array of biological processes. Recently, there has been an upsurge of interest in the interactions between mediators of inflammation and other cells such as stem cells and cancer cells. Since tissue injuries are associated with the release of inflammatory mediators, it would be difficult to address this subject without considering the implications of their systemic effects. In this review, we discuss the effects of inflammatory reactions on stem cells and extrapolate on information pertaining to cancer biology. The discussion focuses on integrins and cytokines, and identifies the transcription factor, nuclear factor-kappa B (NFκB as central to the inflammatory response. Since stem cell therapy has been proposed for type II diabetes mellitus, metabolic syndrome, pulmonary edema, these disorders are used as examples to discuss the roles of inflammatory mediators. We propose prospects for future research on targeting the NFκB signaling pathway. Finally, we explore the bridge between inflammation and stem cells, including neural stem cells and adult stem cells from the bone marrow. The implications of mesenchymal stem cells in regenerative medicine as pertaining to inflammation are vast based on their anti-inflammatory and immunosuppressive effects. Such features of stem cells offer great potential for therapy in graft-versus-host disease, conditions with a significant inflammatory component, and tissue regeneration.Keywords: mesenchymal stem cells, cancer, cytokines

  7. Histamine modifies malignant biological behaviour in irradiated breast cancer cells

    International Nuclear Information System (INIS)

    MDA MB 231, a metastatic breast cancer cell line, expresses the four known types of histamine receptors (HAR), which differentially regulate cell proliferation. HA also exerts a radiosensitizing effect when is added to MDA MB 231 cells before irradiation in a way related to the elevation of H2O2 levels. However, ionizing radiation (IR) has also been demonstrated to affect malignant biological behaviour depending upon cell type and irradiation characteristics. The present study was conducted to investigate the action of HA and IR on two events involved in metastatic capacity such as the expression and activity of matrix metalloproteinases (MMPs) and cell motility. HA decreased MMP2 and MMP9 expression assessed by RT-PCR and cytochemistry as well enzymatic activity determined by zimography. This effect was mimicked by H2 agonists, while an opposite action was mainly observed when H4 agonists were employed. Cell motility, evaluated by wound healing assay, was also distinctly modulated through HAR. It was significantly augmented via H4R and to a lesser extent via H1R and H3R, though diminished through H2R. 2 Gy irradiated cells showed an enhanced MMP2 and MMP9 activity and cell motility compared to control cells. However, this effect was counteracted by HA. Results suggest that HA treatment could improve radiotherapy efficacy regarding the potential development of metastases. (authors)

  8. Natural Killer Cells: Biology and Clinical Use in Cancer Therapy

    Institute of Scientific and Technical Information of China (English)

    William H. D. Hallett; William J. Murphy

    2004-01-01

    Natural killer (NK) cells have the ability to mediate both bone marrow rejection and promote engraftment, as well as the ability to elicit potent anti-tumor effects. However the clinical results for these processes are still elusive. Greater understanding of NK cell biology, from activating and inhibitory receptor functions to the role of NK cells in allogeneic transplantation, needs to be appreciated in order to draw out the clinical potential of NK cells. Mechanisms of bone marrow cell (BMC) rejection are known to be dependant on inhibitory receptors specific for major histocompatibility complex (MHC) molecules and on activating receptors that have many potential ligands. The modulation of activating and inhibitory receptors may hold the key to clinical success involving NK cells. Pre-clinical studies in mice have shown that different combinations of activating and inhibitory receptors on NK cells can reduce graft-versus-host disease (GVHD), promote engraftment, and provide superior graft-versus-tumor (GVT) responses. Recent clinical data have shown that the use of KIR-ligand incompatibility produces tremendous graft-versus-leukemia effect in patients with acute myeloid leukemia at high risk of relapse. This review will attempt to be a synthesis of current knowledge concerning NK cells, their involvement in BMT, and their use as an immunotherapy for cancer and other hematologic malignancies. Cellular & Molecular Immunology. 2004;1(1):12-21.

  9. Cancer Stem Cells: Biological Functions and Therapeutically Targeting

    Directory of Open Access Journals (Sweden)

    Marius Eugen Ciurea

    2014-05-01

    Full Text Available Almost all tumors are composed of a heterogeneous cell population, making them difficult to treat. A small cancer stem cell population with a low proliferation rate and a high tumorigenic potential is thought to be responsible for cancer development, metastasis and resistance to therapy. Stem cells were reported to be involved in both normal development and carcinogenesis, some molecular mechanisms being common in both processes. No less controversial, stem cells are considered to be important in treatment of malignant diseases both as targets and drug carriers. The efforts to understand the role of different signalling in cancer stem cells requires in depth knowledge about the mechanisms that control their self-renewal, differentiation and malignant potential. The aim of this paper is to discuss insights into cancer stem cells historical background and to provide a brief review of the new therapeutic strategies for targeting cancer stem cells.

  10. Mathematical models in cell biology and cancer chemotherapy

    CERN Document Server

    Eisen, Martin

    1979-01-01

    The purpose of this book is to show how mathematics can be applied to improve cancer chemotherapy. Unfortunately, most drugs used in treating cancer kill both normal and abnormal cells. However, more cancer cells than normal cells can be destroyed by the drug because tumor cells usually exhibit different growth kinetics than normal cells. To capitalize on this last fact, cell kinetics must be studied by formulating mathematical models of normal and abnormal cell growth. These models allow the therapeutic and harmful effects of cancer drugs to be simulated quantitatively. The combined cell and drug models can be used to study the effects of different methods of administering drugs. The least harmful method of drug administration, according to a given criterion, can be found by applying optimal control theory. The prerequisites for reading this book are an elementary knowledge of ordinary differential equations, probability, statistics, and linear algebra. In order to make this book self-contained, a chapter on...

  11. Cancer Stem Cells: Biological Functions and Therapeutically Targeting

    OpenAIRE

    Marius Eugen Ciurea; Ada Maria Georgescu; Stefana Oana Purcaru; Stefan-Alexandru Artene; Ghazaleh Hooshyar Emami; Mihai Virgil Boldeanu; Daniela Elise Tache; Anica Dricu

    2014-01-01

    Almost all tumors are composed of a heterogeneous cell population, making them difficult to treat. A small cancer stem cell population with a low proliferation rate and a high tumorigenic potential is thought to be responsible for cancer development, metastasis and resistance to therapy. Stem cells were reported to be involved in both normal development and carcinogenesis, some molecular mechanisms being common in both processes. No less controversial, stem cells are considered to be importan...

  12. Systems Biology of cancer: Moving toward the Integrative Study of the metabolic alterations in cancer cells.

    Directory of Open Access Journals (Sweden)

    Claudia Erika Hernández Patiño

    2013-01-01

    Full Text Available One of the main objectives in systems biology is to understand the biological mechanisms that give rise to the phenotype of a microorganism by using high-throughput technologies and genome-scale mathematical modeling. The computational modeling of genome-scale metabolic reconstructions is one systemic and quantitative strategy for characterizing the metabolic phenotype associated with human diseases and potentially for designing drugs with optimal clinical effects. The purpose of this short review is to describe how computational modeling, including the specific case of constraint-based modeling, can be used to explore, characterize and predict the metabolic capacities that distinguish the metabolic phenotype of cancer cell lines. As we show herein, this computational framework is far from a pure theoretical description, and to ensure proper biological interpretation, it is necessary to integrate high-throughput data and generate predictions for later experimental assessment. Hence, genome-scale modeling serves as a platform for the following: 1 the integration of data from high-throughput technologies, 2 the assessment of how metabolic activity is related to phenotype in cancer cell lines and 3 the design of new experiments to evaluate the outcomes of the in silico analysis. By combining the functions described above, we show that computational modeling is a useful methodology to construct an integrative, systemic and quantitative scheme for understanding the metabolic profiles of cancer cell lines, a first step to determine the metabolic mechanism by which cancer cells maintain and support their malignant phenotype in human tissues.

  13. Study on the biological characteristics of pancreatic cancer vascular endothelial cells

    Institute of Scientific and Technical Information of China (English)

    李雷

    2012-01-01

    Objective To explore the biological characteristics of pancreatic cancer vascular endothelial cells,including the aspects of morphology,species,genetics,vascular formation ability,and proliferation ability in vitro. Methods The human pancreatic cancer cells were inoculated in nude mice pancreas to get pancreatic cancer

  14. Stem cell biology in thyroid cancer: Insights for novel therapies

    Institute of Scientific and Technical Information of China (English)

    Parisha; Bhatia; Koji; Tsumagari; Zakaria; Y; Abd; Elmageed; Paul; Friedlander; Joseph; F; Buell; Emad; Kandil

    2014-01-01

    Currently, thyroid cancer is one of the most common endocrine cancer in the United States. A recent involvement of sub-population of stem cells, cancer stem cells, has been proposed in different histological types of thyroid cancer. Because of their ability of self-renewal and differentiation into various specialized cells in the body, these putative cells drive tumor genesis, metastatic activity and are responsible to provide chemo- and radioresistant nature to the cancer cells in the thyroid gland. Our Review was conducted from previously published literature to provide latest apprises to investigate the role of embryonic, somatic and cancer stem cells, and discusses the hypothesis of epithelial-mesenchymal transition. Different methods for their identification and isolation through stemness markers using various in vivo and in vitro methods such as flow cytometry, thyrosphere formation assay, aldehyde dehydrogenase activity and ATP-binding cassette sub-family G member 2 efflux-pump mediated Hoechst 33342 dye exclusion have been discussed. The review also outlines various setbacks that still remain to target these tumor initiating cells. Future perspectives of therapeutic strategies and their potential to treat advanced stages of thyroid cancer are also disclosed in this review.

  15. Study on biological characters of SGC7901 gastric cancer cell-dendritic cell fusion vaccines

    Institute of Scientific and Technical Information of China (English)

    Kun Zhang; Peng-Fen Gao; Pei-Wu Yu; Yun Rao; Li-Xin Zhou

    2006-01-01

    AIM: To detect the biological characters of the SGC7901 gastric cancer cell-dendritic cell fusion vaccines.METHODS: The suspending living SGC7901 gastric cancer cells and dendritic cells were induced to be fusioned by polyethylene glycol. Pure fusion cells were obtained by selective culture with the HAT/HT culture systems.The fusion cells were counted at different time points of culture and their growth curves were drawn to reflect their proliferative activities. The fusion cells were also cultured in culture medium to investigate whether they could grow into cell clones. MTT method was used to test the stimulating abilities of the fusion cells on T lymphocytes' proliferations. Moreover, the fusion cells were planted into nude mice to observe whether they could grow into new planted tumors in this kind of immunodeficiency animals.RESULTS: The fusion cells had weaker proliferative activity and clone abilities than their parental cells. When they were cultured, the counts of cells did not increase remarkably, nor could they grow into cell clones in culture medium. The fusion cells could not grow into new planted tumors after planted into nude mice. The stimulating abilities of the fusion cells on T lymphocytes' proliferations were remarkably increased than their parental dendritic cells.CONCLUSION: The SGC7901 gastric cancer cell-dendritic cell fusion vaccines have much weaker proliferative abilities than their parental cells, but they keep strong abilities to irritate the T lymphocytes and have no abilities to grow into new planted tumors in immunodeficiency animals. These are the biological basis for their antitumor biotherapies.

  16. Biological characteristics of side population cells in a self-established human ovarian cancer cell line

    Science.gov (United States)

    WEI, ZHENTONG; LV, SHUANG; WANG, YISHU; SUN, MEIYU; CHI, GUANGFAN; GUO, JUN; SONG, PEIYE; FU, XIAOYU; ZHANG, SONGLING; LI, YULIN

    2016-01-01

    The aim of the present study was to establish an ovarian cancer (OC) cell line from ascites of an ovarian serous cystadenocarcinoma patient and investigate the biological characteristics of its side population (SP) cells. The OC cell line was established by isolating, purifying and subculturing primary cells from ascites of an ovarian serous cystadenocarcinoma patient (stage IIIc; grade 3). SP and non-SP (NSP) cells were isolated by fluorescence-activated cell sorting and cultured in serum-free medium and soft agar to compare the tumorsphere and colony formation capacities. Furthermore, SP and NSP cell tumorigenesis was examined by subcutaneous and intraperitoneal injection of the cells to non-obese diabetic/severe combined immune deficiency (NOD/SCID) mice. Drug resistance to cisplatin was examined by cell counting kit-8. The OC cell line was successfully established from ascites of an ovarian serous cystadenocarcinoma patient, which exhibited properties similar to primary tumors subsequent to >50 passages and >2 years of culture. The SP cell ratio was 0.38% in the OC cell line, and a similar SP cell ratio (0.39%) was observed when sorted SP cells were cultured for 3 weeks. Compared with NSP cells, SP cells exhibited increased abilities in differentiation and tumorsphere and colony formation, in addition to the formation of xenografted tumors and ascites and metastasis of the tumors in NOD/SCID mice, even at low cell numbers (3.0×103 cells). The xenografted tumors demonstrated histological features similar to primary tumors and expressed the ovarian serous cystadenocarcinoma marker CA125. In addition, SP cells demonstrated a significantly stronger drug resistance to cisplatin compared with NSP and unsorted cells, while treatment with verapamil, an inhibitor of ATP-binding cassette transporters, potently abrogated SP cell drug resistance. In conclusion, the present study verified SP cells from an established OC cell line and characterized the cells with self

  17. Immunglobulin Expression and Its Biological Significance in Cancer Cells

    Institute of Scientific and Technical Information of China (English)

    Duosha Hu; Hui Zheng; Haidan Liu; Ming Li; Wei Ren; Wei Liao; Zhi Duan; Lili Li; Ya Cao

    2008-01-01

    It is generally believed that the expression of a gene iS restricted "within the right place and at the right time".This principle has long been considered applicable as well to the expression of immunoglobulin(Ig)lymphocytes of B cell lineage.However,increasing evidence has shown Ig "paradoxically" expressed in malignant tumors of epitheliaI origin.We reviewed the recent progress in the study of cancer-derived Ig,and also discussed its mechanisms and possible functions,trying to arouse interest and attention to those working in the field of immunology and oncology.

  18. Biological Therapy Following Chemotherapy and Peripheral Stem Cell Transplantation in Treating Patients With Cancer

    Science.gov (United States)

    2013-03-25

    Breast Cancer; Chronic Myeloproliferative Disorders; Gestational Trophoblastic Tumor; Kidney Cancer; Leukemia; Lymphoma; Multiple Myeloma and Plasma Cell Neoplasm; Myelodysplastic Syndromes; Neuroblastoma; Ovarian Cancer; Sarcoma; Testicular Germ Cell Tumor

  19. Simulated weightlessness alters biological characteristics of human breast cancer cell line MCF-7

    Science.gov (United States)

    Qian, Airong; Zhang, Wei; Xie, Li; Weng, Yuanyuan; Yang, Pengfei; Wang, Zhe; Hu, Lifang; Xu, Huiyun; Tian, Zongcheng; Shang, Peng

    The aim of this study is to investigate the effects of the clinostat-simulated microgravity on MCF-7 cells (a breast cancer cell line) biological characteristics. MCF-7 cells were incubated for 24 h in an incubator and then rotated in a clinostat as a model of simulated microgravity for 24, 48 and 72 h, respectively. The effects of the clinostat-simulated microgravity on MCF-7 cells proliferation, invasion, migration, gelatinase production, adhesion, cell cycle, apoptosis and vinculin expression were detected. The results showed that the clinostat-simulated microgravity affected breast cancer cell invasion, migration, adhesion, cell cycle, cell apoptosis and vinculin expression. These results may explore a new field of vision to study tumor metastasis in future.

  20. Effect of survivin siRNA on biological behaviour of breast cancer MCF7 cells

    Institute of Scientific and Technical Information of China (English)

    Hao Wang; Yi-Feng Ye

    2015-01-01

    Objective:To investigate the expression of survivin in breast cancer cell lines and explore the effect of survivin siRNA on biology behavior of breast cancer cells.Methods: Western blot was performed to detect the expression of survivin in breast cancer cell lines. Eukaryotic expression vector pIRES2-EGFP-Survivin siRNA was constructed and transfected in MCF7 cells with liposome, the efficiency of survivin siRNA was measured by Western blot and RT-PCR. Cell proliferation and apoptosis were detected by CCK8 and cell flow respectively. Cell migration and invasion was measured by transwell assay.Results: Survivin was highly expressed in MCF-7. Green fluorescence was found in MCF-7 cells tranfected with survivin siRNA and control siRNA by inverted fluorescence microscopy, the protein and mRNA level of survivin was significantly lower in cells tranfected with survivin siRNA compared with control group. Compared with control group, interfering the expression of survivin by siRNA significantly decreased the proliferation, migration and invasion of MCF-7 cells, the percentage of apoptosis cells was greatly promoted.Conclusions: Interfering the expression of Survivin can inhibit the cell proliferation, migration and invasion, and promot apoptosis in MCF-7.

  1. The Biological Effect of Hepsin on the Proliferation and Invasion of PC-3 Prostate Cancer Cells

    Institute of Scientific and Technical Information of China (English)

    Yong Xu; Zhiqiang Fan; Jantao Sun; Ranlu Liu; Weiming Zhao; Chunyu Wang; Ju Zhang

    2006-01-01

    OBJECTIVE Recent studies have shown that hepsin, a type of transmembrane serine protease, is highly upregulated in prostate cancer, but, little is known about its role in progression and invasion of this cancer. We constructed a hepsin-expressing plasmid and transfected it into PC-3 cells to investigate the effect of the hepsin gene on the biological behavior of the PC-3 cells.METHODS Plasmid pHepsin-IRES2 was transfected into prostate cancer PC-3 cells using Fugene6, and the cells with stable hepsin expression were screened and selected with Zeocin (600 mg/L). The hepsin mRNA level was measured by real-time PCR and the growth curve of the PC-3-transfected cells assessed using MTT and BrdU assays. A Boyden chamber was used to examine the difference in invasion and metastases between transfected and non-transfected cells.RESULTS The hepsin mRNA level in pHepsin-IRES2 transfected -PC-3 cells was significantly higher than that found in the control PC-3 cells. While the growth curve of the hepsin gene transfected PC-3 cells showed that there was no significant effect on proliferation, the invasive ability of the pHepsin-IRES2 transfected PC-3 cells, as compared with control cells, was significantly increased (P<0.05).CONCLUSION The results suggest that even though hepsin has no effect on the proliferation of prostate cancer PC-3 cells, it does promote cellular invasion and metastasis.Therefore hepsin may have a role in the development of prostate cancer.

  2. Molecular biology of breast cancer metastasis Molecular expression of vascular markers by aggressive breast cancer cells

    International Nuclear Information System (INIS)

    During embryogenesis, the formation of primary vascular networks occurs via the processes of vasculogenesis and angiogenesis. In uveal melanoma, vasculogenic mimicry describes the 'embryonic-like' ability of aggressive, but not nonaggressive, tumor cells to form networks surrounding spheroids of tumor cells in three-dimensional culture; these recapitulate the patterned networks seen in patients' aggressive tumors and correlates with poor prognosis. The molecular profile of these aggressive tumor cells suggests that they have a deregulated genotype, capable of expressing vascular phenotypes. Similarly, the embryonic-like phenotype expressed by the aggressive human breast cancer cells is associated with their ability to express a variety of vascular markers. These studies may offer new insights for consideration in breast cancer diagnosis and therapeutic intervention strategies

  3. Implication of stem cells in the biology and therapy of head and neck cancer [

    Directory of Open Access Journals (Sweden)

    Wollenberg, Barbara

    2012-04-01

    tumours is expected. Those occur in tumours and they have typical stem cell characteristics like self-regeneration and the potential of differentiation and are potentially responsible for tumour growth. With their ability of self-regeneration they would have the ability to form a complete tumour out of every single cell. That tumour would histologically look like the tumour those cells initially originated from. Of particular interest regarding those currently still elusive cancer stem cells is their resistance towards current therapies like radiotherapy or chemotherapy. Those insights now get a completely new meaning in tumour biology: Does a cancer stem cell exist, which is able to initiate and keep up tumour growth despite all possible therapeutic interventions? This presentation will outline the current views regarding cancer stem cells in non HPV associated HNSCC and it will highlight problems, which are currently researched on. The objective must be to understand the biology of those cells in a way that make an extended range of therapeutics possible. A therapy, which specifically targets cancer stem cells, could improve the chances of recovery.

  4. Biological and clinical implications of cancer stem cells in primary brain tumors

    Directory of Open Access Journals (Sweden)

    RuggeroDe Maria

    2013-01-01

    Full Text Available Despite therapeutic advances, glioblastoma multiforme (GBM remains a lethal disease. The infiltrative nature of this disease and the presence of a cellular population resistant to current medical treatments account for the poor prognosis of these patients. Growing evidence indicates the existence of a fraction of cancer cells sharing the functional properties of adult stem cells, including self-renewal and a greater ability to escape chemo-radiotherapy-induced death stimuli. Therefore, these cells are commonly defined as cancer stem cells (GBM-SCs. The initial GBM-SC concept has been challenged, and refined according to the emerging molecular taxonomy of GBM. This allowed to postulate the existence of multiple CSC types, each one driving a given molecular entity. Furthermore, it is becoming increasingly clear that GBM-SCs thrive through a dynamic and bidirectional interaction with the surrounding microenvironment. In this article, we discuss recent advances in GBM-SC biology, mechanisms through which these cells adapt to hostile conditions, pharmacological strategies for selectively killing GBM-SCs, and how novel CSC-associated endpoints have been investigated in the clinical setting.

  5. Regulatory T Cells in Colorectal Cancer: From Biology to Prognostic Relevance

    International Nuclear Information System (INIS)

    Regulatory T cells (Tregs) were initially described as “suppressive” lymphocytes in the 1980s. However, it took almost 20 years until the concept of Treg-mediated immune control in its present form was finally established. Tregs are obligatory for self-tolerance and defects within their population lead to severe autoimmune disorders. On the other hand Tregs may promote tolerance for tumor antigens and even hamper efforts to overcome it. Intratumoral and systemic accumulation of Tregs has been observed in various types of cancer and is often linked to worse disease course and outcome. Increase of circulating Tregs, as well as their presence in mesenteric lymph nodes and tumor tissue of patients with colorectal cancer de facto suggests a strong involvement of Tregs in the antitumor control. This review will focus on the Treg biology in view of colorectal cancer, means of Treg accumulation and the controversies regarding their prognostic significance. In addition, a concise overview will be given on how Tregs and their function can be targeted in cancer patients in order to bolster an inherent immune response and/or increase the efficacy of immunotherapeutic approaches

  6. Regulatory T Cells in Colorectal Cancer: From Biology to Prognostic Relevance

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    Mougiakakos, Dimitrios [Department of Oncology and Pathology, Immune and Gene Therapy Unit, Cancer Centre Karolinska, CCK R8:01, 17176 Stockholm (Sweden)

    2011-03-29

    Regulatory T cells (Tregs) were initially described as “suppressive” lymphocytes in the 1980s. However, it took almost 20 years until the concept of Treg-mediated immune control in its present form was finally established. Tregs are obligatory for self-tolerance and defects within their population lead to severe autoimmune disorders. On the other hand Tregs may promote tolerance for tumor antigens and even hamper efforts to overcome it. Intratumoral and systemic accumulation of Tregs has been observed in various types of cancer and is often linked to worse disease course and outcome. Increase of circulating Tregs, as well as their presence in mesenteric lymph nodes and tumor tissue of patients with colorectal cancer de facto suggests a strong involvement of Tregs in the antitumor control. This review will focus on the Treg biology in view of colorectal cancer, means of Treg accumulation and the controversies regarding their prognostic significance. In addition, a concise overview will be given on how Tregs and their function can be targeted in cancer patients in order to bolster an inherent immune response and/or increase the efficacy of immunotherapeutic approaches.

  7. Synthesis of novel flavone derivatives possessing substituted benzamides and their biological evaluation against human cancer cells.

    Science.gov (United States)

    Yun, Bo Hee; Lee, Young Hun; Park, Kyung Tae; Jung, Su Jin; Lee, Yong Sup

    2016-09-01

    Baicalein is a well-known flavone derivative that possesses diverse biological properties, such as anticancer, antioxidant and anti-inflammatory activities. Numerous baicalein derivatives, including 5,6,7-trimethoxyflavone, have been synthesized with the aim of enhancing its inherent biological activities. In the present work, new flavones, possessing an N-aroylamine-substituent on the B-ring, were synthesized to improve the cytotoxicity of baicalein and 5,6,7-trimethoxyflavone against human cancer cell lines. The majority of the flavones synthesized exhibited greater cytotoxicity than baicalein and 5,6,7-trimethoxyflavone against HepG2 and MCF-7 cells. Among them, compounds 5n, possessing a 3-methoxybenzoylamino group, exhibited great cytotoxic effects on HepG2 (GI50=7.06μM) and MCF-7 (GI50=7.67μM) cells. In contrast, N-aroylamine-substituted 5-hydroxy-6,7-dimethoxyflavone derivatives showed greater cytotoxicity against MCF-7 than HepG2 cells, indicating that the replacement of a 5-methoxy group on the A-ring with a 5-hydroxy group has a marked influence on the cytotoxicity profile. PMID:27503682

  8. Abnormal expression of calcyphosine is associated with poor prognosis and cell biology function in colorectal cancer

    Directory of Open Access Journals (Sweden)

    Shao W

    2016-01-01

    Full Text Available Weiwei Shao,* Quhui Wang,* Feiran Wang, Yasu Jiang, Meirong Xu, Junfei XuDepartment of General Surgery, Affiliated Hospital of Nantong University, Nantong, People’s Republic of China*These authors contributed equally to this workAbstract: The aim of this study was to investigate the calcyphosine (CAPS expression in human colorectal cancer (CRC and to explore its clinical and prognostic significances. CAPS expression was measured by Western blot, real-time polymerase chain reaction analysis, and immunohistochemistry. The relationships between the CAPS expression levels and the clinicopathological factors were investigated. The Kaplan–Meier method and log-rank test were used to investigate the overall survival of the patients. Moreover, the effects of CAPS on biological roles of CRC cells were also evaluated by MTT assay, colony formation assay, and transwell assay. CAPS was significantly overexpressed in cancerous tissue and CRC cell lines compared with adjacent nontumor tissue and a normal human intestinal epithelial cell line. Overexpression of CAPS was significantly associated with histological grade (P=0.004, invasive depth (P<0.001, lymph node metastasis (P=0.003, tumor node metastasis stage (P=0.017, and distant metastasis (P=0.042. Furthermore, silencing of CAPS expression in CRC cells inhibited their proliferation, colony formation, migration, and invasion. Kaplan–Meier survival analysis showed that high CAPS expression might demonstrate poor prognosis in CRC patients. Cox regression analysis revealed that CAPS expression was an independent prognostic factor of CRC. Our data suggested that the upregulation of CAPS might play a role in the carcinogenesis and progression of CRC. CAPS could be used as a potential diagnostic factor and be an independent good prognostic indicator for CRC patients.Keywords: calcyphosine, colorectal cancer, prognosis

  9. Genetics and molecular biology of breast cancer

    Energy Technology Data Exchange (ETDEWEB)

    King, M.C. [California Univ., Berkeley, CA (United States); Lippman, M. [Georgetown Univ. Medical Center, Washington, DC (United States)] [comps.

    1992-12-31

    This volume contains the abstracts of oral presentations and poster sessions presented at the Cold Springs Harbor Meeting on Cancer Cells, this meeting entitled Genetics and Molecular Biology of Breast Cancer.

  10. Prognostic Cell Biological Markers in Cervical Cancer Patients Primarily Treated With (Chemo)radiation: A Systematic Review

    International Nuclear Information System (INIS)

    The aim of this study was to systematically review the prognostic and predictive significance of cell biological markers in cervical cancer patients primarily treated with (chemo)radiation. A PubMed, Embase, and Cochrane literature search was performed. Studies describing a relation between a cell biological marker and survival in ≥50 cervical cancer patients primarily treated with (chemo)radiation were selected. Study quality was assessed, and studies with a quality score of 4 or lower were excluded. Cell biological markers were clustered on biological function, and the prognostic and predictive significance of these markers was described. In total, 42 studies concerning 82 cell biological markers were included in this systematic review. In addition to cyclooxygenase-2 (COX-2) and serum squamous cell carcinoma antigen (SCC-ag) levels, markers associated with poor prognosis were involved in epidermal growth factor receptor (EGFR) signaling (EGFR and C-erbB-2) and in angiogenesis and hypoxia (carbonic anhydrase 9 and hypoxia-inducible factor-1α). Epidermal growth factor receptor and C-erbB-2 were also associated with poor response to (chemo)radiation. In conclusion, EGFR signaling is associated with poor prognosis and response to therapy in cervical cancer patients primarily treated with (chemo)radiation, whereas markers involved in angiogenesis and hypoxia, COX-2, and serum SCC-ag levels are associated with a poor prognosis. Therefore, targeting these pathways in combination with chemoradiation may improve survival in advanced-stage cervical cancer patients.

  11. Polyphenol-rich strawberry extract (PRSE) shows in vitro and in vivo biological activity against invasive breast cancer cells.

    Science.gov (United States)

    Amatori, Stefano; Mazzoni, Luca; Alvarez-Suarez, Josè Miguel; Giampieri, Francesca; Gasparrini, Massimiliano; Forbes-Hernandez, Tamara Yuliett; Afrin, Sadia; Errico Provenzano, Alfredo; Persico, Giuseppe; Mezzetti, Bruno; Amici, Augusto; Fanelli, Mirco; Battino, Maurizio

    2016-01-01

    We describe the biological effects of a polyphenol-rich strawberry extract (PRSE), obtained from the "Alba" variety, on the highly aggressive and invasive basal-like breast cancer cell line A17. Dose-response and time-course experiments showed that PRSE is able to decrease the cellular viability of A17 cells in a time- and dose-dependent manner. PRSE effect on cell survival was investigated in other tumor and normal cell lines of both mouse and human origin, demonstrating that PRSE is more active against breast cancer cells. Cytofluorimetric analysis of A17 cells demonstrated that sub-lethal doses of PRSE reduce the number of cells in S phase, inducing the accumulation of cells in G1 phase of cell cycle. In addition, the migration of A17 cells was studied monitoring the ability of PRSE to inhibit cellular mobility. Gene expression analysis revealed the modulation of 12 genes playing different roles in the cellular migration, adhesion and invasion processes. Finally, in vivo experiments showed the growth inhibition of A17 cells orthotopically transplanted into FVB syngeneic mice fed with PRSE. Overall, we demonstrated that PRSE exerts important biological activities against a highly invasive breast cancer cell line both in vitro and in vivo suggesting the strawberry extracts as preventive/curative food strategy. PMID:27498973

  12. Proteomics-Based Analysis of Protein Complexes in Pluripotent Stem Cells and Cancer Biology.

    Science.gov (United States)

    Sudhir, Putty-Reddy; Chen, Chung-Hsuan

    2016-01-01

    A protein complex consists of two or more proteins that are linked together through protein-protein interactions. The proteins show stable/transient and direct/indirect interactions within the protein complex or between the protein complexes. Protein complexes are involved in regulation of most of the cellular processes and molecular functions. The delineation of protein complexes is important to expand our knowledge on proteins functional roles in physiological and pathological conditions. The genetic yeast-2-hybrid method has been extensively used to characterize protein-protein interactions. Alternatively, a biochemical-based affinity purification coupled with mass spectrometry (AP-MS) approach has been widely used to characterize the protein complexes. In the AP-MS method, a protein complex of a target protein of interest is purified using a specific antibody or an affinity tag (e.g., DYKDDDDK peptide (FLAG) and polyhistidine (His)) and is subsequently analyzed by means of MS. Tandem affinity purification, a two-step purification system, coupled with MS has been widely used mainly to reduce the contaminants. We review here a general principle for AP-MS-based characterization of protein complexes and we explore several protein complexes identified in pluripotent stem cell biology and cancer biology as examples. PMID:27011181

  13. Network systems biology for targeted cancer therapies

    Institute of Scientific and Technical Information of China (English)

    Ting-Ting Zhou

    2012-01-01

    The era of targeted cancer therapies has arrived.However,due to the complexity of biological systems,the current progress is far from enough.From biological network modeling to structural/dynamic network analysis,network systems biology provides unique insight into the potential mechanisms underlying the growth and progression of cancer cells.It has also introduced great changes into the research paradigm of cancer-associated drug discovery and drug resistance.

  14. Fetal Cell Microchimerism and Cancer: A Nexus of Reproduction, Immunology and Tumor Biology

    OpenAIRE

    Kallenbach, Lisa R.; Johnson, Kirby L.; Bianchi, Diana W.

    2011-01-01

    Fetal cell microchimerism (FCM) is the persistence of fetal cells in the maternal circulation and organs following pregnancy. Proposed hypotheses regarding the function of fetal cells in the pathogenesis of maternal cancer include promotion of tumorigenesis, protection by providing immunosurveillance, and participation in tissue repair. To date, studies of FCM and cancer have been primarily descriptive and quantitative. More research is needed to understand the cellular phenotype of the micro...

  15. Expression of transcription factor Klf8 in lung cancer tissue and the biological effect of downregulation of Klf8 expression in lung cancer cell lines

    Institute of Scientific and Technical Information of China (English)

    Xuan-Hong Yi; Jing Wang

    2016-01-01

    Objective:To study the expression of transcription factor Klf8 in lung cancer tissue and the biological effect of downregulation of Klf8 expression in lung cancer cell lines.Methods:Cancer tissue and adjacent normal lung tissue were collected and mRNA contents of Klf8 were detected; lung cancer A549 cell lines were cultured, and after transfection of Klf8 siRNA, cell cycle, cell invasion and epithelial-mesenchymal transition were detected.Results:mRNA contents of Klf8 in lung cancer tissue were higher than those in adjacent normal lung tissue; after transfection of Klf8 siRNA, Klf8 mRNA inhibition rate was 74.31%; G0/G1 phase ratio of Klf8 siRNA group was higher than that of negative control siRNA group; ratios of S-phase and G2/M phase cells, mRNA contents of Cyclin D1 and number of cells invading to the outer side of the transwell microporous membrane were lower than those of negative control siRNA group; mRNA contents of CDH1 and CK18 as well as Snail and Slug of Klf8 siRNA group were higher than those of negative control siRNA group; mRNA contents of VIM and N-cadherin were lower than those of negative control siRNA group.Conclusion:The expression of Klf8 in lung cancer tissue abnormally elevates; downregulation of Klf8 expression in lung cancer cell lines can inhibit malignant biological effect of cells, manifested as cell cycle arrest as well as the inhibition of cell invasion and epithelial-mesenchymal transition processes.

  16. Concise Review: Stem Cells and Epithelial-Mesenchymal Transition in Cancer: Biological Implications and Therapeutic Targets.

    Science.gov (United States)

    Sato, Ryo; Semba, Takashi; Saya, Hideyuki; Arima, Yoshimi

    2016-08-01

    Cancer stem cells (CSCs) constitute a small subpopulation of cancer cells with stem-like properties that are able to self-renew, generate differentiated daughter cells, and give rise to heterogeneous tumor tissue. Tumor heterogeneity is a hallmark of cancer and underlies resistance to anticancer therapies and disease progression. The epithelial-mesenchymal transition (EMT) is a reversible phenomenon that is mediated by EMT-inducing transcription factors (EMT-TFs) and plays an important role in normal organ development, wound healing, and the invasiveness of cancer cells. Recent evidence showing that overexpression of several EMT-TFs is associated with stemness in cancer cells has suggested the existence of a link between EMT and CSCs. In this review, we focus on the roles of CSCs and EMT signaling in driving tumor heterogeneity. A better understanding of the dynamics of both CSCs and EMT-TFs in the generation of tumor heterogeneity may provide a basis for the development of new treatment options for cancer patients. Stem Cells 2016;34:1997-2007. PMID:27251010

  17. Effect of TRAF6 Downregulation on Malignant Biological Behavior of
Lung Cancer Cell Lines

    Directory of Open Access Journals (Sweden)

    Gen LIN

    2015-11-01

    Full Text Available Background and objective It has been proven that tumor necrosis factor receptor-associated factor 6 (TRAF6 was a commonly amplified oncogene in lung cancer. However, the precise role of TRAF6 protein in lung cancer has not been extensively investigated. This study analyzed the effects of TRAF6 on the proliferation, apoptosis, cell cycle, migration, and invasion capability of lung cancer cell lines, as well as the potential molecular mechanisms involved. Methods To address the expression of TRAF6 in lung cancer cells, four lung cancer cell lines (A549, H1650, SPC-A-1 and Calu-3 were assayed to determine the expression of TRAF6 protein by Western blot and TRAF6 mRNA via qRT-PCR. Moreover, siRNA targeting TRAF6 was introduced into SPC-A-1 and Calu-3 cells. Nuclear factor-қB (NF-қB DNA-binding activity, apoptosis rates, cell proliferation, cell cycle, migration, and invasion were determined by electrophoretic mobility shift assay, flow cytometry, MTS assay, flow cytometry, scratch test, and transwell chamber assay, respectively. Western blot analysis was also performed to evaluate the expression of the following proteins through K63-ubiquitination: P65, CD24 and CXCR4. Whole-genome sequencing analysis was conducted using a second-generation sequencer in SPC-A-1 cells. Results TRAF6 was highly up-expressed in SPC-A-1 and Calu-3 cell lines than the other two cells, which also showed K63-ubiquitinization in TRAF6. However, constitutive activation of NF-қB was observed only in SPC-A-1 lung cancer cells. Downregulation of TRAF6 suppressed the NF-κB activation, cell migration, and invasion but promoted the cell apoptosis of SPC-A-1 cells. Markedly decreased expression of CD24 and CXCR4 was observed in SPC-A-1 cells transfected by TRAF6 siRNA. Nevertheless, TRAF6 downregulation did not affect the proliferation and cell cycle of SPC-A-1 cells. Additionally, TRAF6 regulation did not affect the proliferation, apoptosis, cell cycle, migration, and invasion

  18. Atmospheric-pressure plasma-jet from micronozzle array and its biological effects on living cells for cancer therapy

    Science.gov (United States)

    Kim, Kangil; Choi, Jae Duk; Hong, Yong Cheol; Kim, Geunyoung; Noh, Eun Joo; Lee, Jong-Soo; Yang, Sang Sik

    2011-02-01

    We propose a plasma-jet device with a micrometer-sized nozzle array for use in a cancer therapy. Also, we show the biological effects of atmospheric-pressure plasma on living cells. Nitrogen-plasma activated a surrogate DNA damage signal transduction pathway, called the ataxia telangiectasia mutated (ATM)-checkpoint kinase 2 pathway, suggesting that the nitrogen-plasma generates DNA double-strand breaks. Phosphorylation of H2AX and p53 was detected in the plasma-treated cells, leading to apoptotic cell death. Thus, an effect for the nitrogen plasma in the control of apoptotic cell death provides insight into the how biological effects of the nitrogen-plasma can be applied to the control of cell survival, a finding with potential therapeutic implications.

  19. Biologic Therapy (Immunotherapy) for Kidney Cancer

    Science.gov (United States)

    ... for kidney cancer Targeted therapies for kidney cancer Biologic therapy (immunotherapy) for kidney cancer Chemotherapy for kidney cancer Pain control for kidney cancer Treatment choices by stage for ...

  20. The Expression and Biological Significance of PD-L1 on Lung Cancer Cell Lines

    Directory of Open Access Journals (Sweden)

    Cheng CHEN

    2009-08-01

    Full Text Available Background and objective Tumor-associated PD-L1 expression was recently shown to promote T-cell apoptosis and proposed as a potential mechanism of immune evasion by tumors. On the basis of the ability of tumor-associated PD-L1 to mediate activated T-cell death, it is likely that manipulation of the PD-L1 pathway at defined time points during the development of the T-cell antitumor immune response can enhance the efficacy of T-cell-based immunotherapy. Here, the levels of expression of PD-L1 on lung cancer cell lines and its role in interaction of CTL and target cells was investigated. Methods Human PBMC derived DCs were loaded with apoptotic tumor cells and stimulated by CD40 mAb (5C11. Tumor specific CTL was generated in vitro by autologous T cells co-cultured with mature DCs. Expression of PD-L1 on lung cancer cell lines H1299 and A549 were analyzed by FCM. JAM assay was used to detect the cytolytic activity of CTL with or without blocking PD-L1 by PD-L1 mAb respectively. The concentrations of IFN-γ in supernatants from distinct groups were analyzed by ELISA. Results Tumor cells-loaded mature DCs could induce the generation of the tumor specific CTL. Expression of PD-L1 was low on A549 cell, but high on H1299 cell. Blockade of PD-L1 on A549 could not improve cytolytic effect of CTL on target cells and IFN-γ production, but fragmentation of H1299 cells and IFN-γ production were significantly enhanced by the combination of PD-L1 mAb and CTL. Conclusion Expression of PD-L1 on lung cancer cell line can decrease the cytolytic effect of CTL on target cells.

  1. Cell biology as the basis of a better understanding of cancer

    OpenAIRE

    Wheatley Denys N

    2005-01-01

    Abstract Clinicians will argue that cancer can only really receive the treatment that is needed through thorough understanding of medicine. However, even empirical approaches to therapy result in experimental analysis of the agencies involved on test cells, usually in culture. From the obverse perspective, cell biologists will argue that until we fully understand cell cycle regulation, tumour management will be too imprecise to make the best advances. A forum is needed whereby the fundamental...

  2. Cell biology as the basis of a better understanding of cancer

    Directory of Open Access Journals (Sweden)

    Wheatley Denys N

    2005-11-01

    Full Text Available Abstract Clinicians will argue that cancer can only really receive the treatment that is needed through thorough understanding of medicine. However, even empirical approaches to therapy result in experimental analysis of the agencies involved on test cells, usually in culture. From the obverse perspective, cell biologists will argue that until we fully understand cell cycle regulation, tumour management will be too imprecise to make the best advances. A forum is needed whereby the fundamental studies on cells prior to, during and after transformation in vitro can be freely reported (open access and discussed. The action of anticancer agents and cancer preventative substances can more easily be studied in vitro before the often excessive complexity of making similar studies in experimental and human cancers is tackled. Cancer Cell International is committed to providing such a forum. Ironically within a few months of launching this open access journal, Elsevier had much the same idea, and there one has to pay for the privilege of downloading vital papers in this biomedical field.

  3. Targeted therapies for non-small-cell lung cancer: biology, rationale, and preclinical results from a radiation oncology perspective

    International Nuclear Information System (INIS)

    The epidermal growth factor receptor (EGFR) is overexpressed in the majority of non-small-cell lung cancers (NSCLCs). This presents an opportune target for new treatment strategies designed to selectively interfere with the cancer cell growth cycle. Recent investigations into the biology of the EGFR and its downstream signaling pathways have reminded us of the complexity of cancer cell communications from the cytoplasm to the nucleus. Multiple pathways are activated with stimulation of the autocrine and paracrine EGFR loop, from the ras-raf-MEK activation of ERK 1/2 to the P13K-Akt pathway, each playing an important role in cancer cell survival, invasion, and angiogenesis. Preclinical studies have demonstrated that molecules targeting the EGFR, either through extracellular blockade or intracellular interference with the EGFR-associated tyrosine kinase, reversibly or irreversibly, inhibit cancer cell growth. Potent antitumor effects have been observed in human tumor xenograft models. Preclinical studies have also demonstrated cooperative effects when anti-EGFR agents are combined with radiation or chemotherapy. Many of these agents have now entered into advanced human clinical trials with modest dose-related toxicity despite chronic administration. Encouraging response rates with single-agent targeted therapy have been reported in heavily pretreated patients with advanced NSCLC. In addition, agents targeting the angiogenic pathway, which plays a key role in the regulation of angiogenesis, may play an important role in enhancing the efficacy of anti-EGFR agents. This article will focus on the biology, rationale, and preclinical studies with targeted anti-EGFR and antiangiogenic therapies for the management of NSCLC

  4. A New Biological Feature of Natural Killer Cells: The Recognition of Solid Tumor-Derived Cancer Stem Cells

    Science.gov (United States)

    Tallerico, Rossana; Garofalo, Cinzia; Carbone, Ennio

    2016-01-01

    Natural killer (NK) cells are classified as a member of the innate lymphoid cells (ILCs) group 1. ILCs have been recently identified and grouped on the basis of their phenotypical and functional characteristics. They are effectors of innate immunity and are involved in secondary lymphoid organ generation and tissue remodeling. NK cells are powerful cytotoxic lymphocytes able to recognize and eliminate tumor- and virus-infected cells by limiting their spread and tissue damage. The recognition of tumor cells is mediated by both activating and inhibitory receptors. While in hematological malignancies the role played by NK cells is widely known, their role in recognizing solid tumors remains unclear. Recently, tumor cell populations have been divided into two compartments: cancer-initiating cells (CICs) or cancer stem cells (CSCs) and senescent tumor cells. Here, CSC will be used. CSCs are a small subset of malignant cells with stem-like properties that are involved in tumor maintenance and recurrence due to their ability to survive to traditional therapies; they are, moreover, poorly recognized by T lymphocytes. Recent data showed that NK cells recognize in vitro cancer-initiating cells derived from colon cancer, glioblastoma, and melanoma. However, more in vivo studies are urgently required to fully understand whether these new antitumor NK cells with cytotoxic capability may be considered in the design of new immunotherapeutic interventions. PMID:27242786

  5. Cytotoxicity of Biologically Synthesized Silver Nanoparticles in MDA-MB-231 Human Breast Cancer Cells

    OpenAIRE

    Sangiliyandi Gurunathan; Jae Woong Han; Vasuki Eppakayala; Muniyandi Jeyaraj; Jin-Hoi Kim

    2013-01-01

    Silver nanoparticles (AgNPs) have been used as an antimicrobial and disinfectant agents. However, there is limited information about antitumor potential. Therefore, this study focused on determining cytotoxic effects of AgNPs on MDA-MB-231 breast cancer cells and its mechanism of cell death. Herein, we developed a green method for synthesis of AgNPs using culture supernatant of Bacillus funiculus, and synthesized AgNPs were characterized by various analytical techniques such as UV-visible spe...

  6. Effect of deleted pancreatic cancer locus 4 gene transfection on biological behaviors of human colorectal carcinoma cells

    Institute of Scientific and Technical Information of China (English)

    De-Sheng Xiao; Ji-Fang Wen; Jing-He Li; Zhong-Liang Hu; Hui Zheng; Chun-Yah Fu

    2005-01-01

    AIMS: To investigate the effect of deleted pancreatic cancer locus 4 (DPC4) gene transfection on biological behaviors of human colorectal carcinoma cells and the role of DPC4 gene in colorectal carcinogenesis.METHODS: PcDNA3.1-DPC4 plasmid was re-constructed by gene-recombination technology. SW620 cells, a human colorectal carcinoma cell line, were transfected with PcDNA3.1-DPC4 plasmid using lipofectamine transfecting technique. Transfected cells were selected with G418.Expression of Smad4 protein was detected in cells transfected with DPC4 gene by immunohistochemistry and Western blot. Biological characterristics of transfected cells were evaluated by population-doubling time and cloning efficiency. Alterations of percentage of S phage cells (S%) and apoptosis rate were determined by flowcytometry.RESULTS: PcDNA3.1-DPC4 plasmid was constructed successfully. SW620 cells transfected with PcDNA3.1-DPC4plasmid (DPC4+-SW620 cells) showed a strong intracellular expression of Smad4 protein, and the positive signal was localized in cytoplasm and nuclei, mainly in cytoplasm,where the expressions of Smad4 protein in SW620 cells transfected with PcDNA3.1 plasmid (PcDNA3.1-SW620 cells)and non-transfected SW620 cells (SW620 cells) were weaker than those in DPC4+-SW620 cells. The populationdoubling time in DPC4+-SW620 cells (116 h) was significantly longer than that in SW620 cells (31 h) and PcDNA3.1-Sw620 cells (29 h) (P<0.01). The cloning efficiencies of DPC4+-SW620 cells (12%) were markedly lower than those of SW620 cells (69%) and PcDNA3.1-Sw620 cells (67%) (P<0.01). Compared with SW620 cells and PcDNA3.1-Sw620 cells, the G0-G1% of DPC4+-SW620cells was obviously higher and the S% was markedly lower (P<0.05). Apoptosis rate of DPC4+-SW620 cells was significantly higher than that of SW620 cells and PcDNA3.1-SW620 cells.CONCLUSION: PcDNA3.1-DPC4 plasmid can be successfully re-constructed and stably transfected into human SW620 cells, thereby the cells can steadily

  7. Biological and Molecular Effects of Small Molecule Kinase Inhibitors on Low-Passage Human Colorectal Cancer Cell Lines

    Directory of Open Access Journals (Sweden)

    Falko Lange

    2014-01-01

    Full Text Available Low-passage cancer cell lines are versatile tools to study tumor cell biology. Here, we have employed four such cell lines, established from primary tumors of colorectal cancer (CRC patients, to evaluate effects of the small molecule kinase inhibitors (SMI vemurafenib, trametinib, perifosine, and regorafenib in an in vitro setting. The mutant BRAF (V600E/V600K inhibitor vemurafenib, but also the MEK1/2 inhibitor trametinib efficiently inhibited DNA synthesis, signaling through ERK1/2 and expression of genes downstream of ERK1/2 in BRAF mutant cells only. In case of the AKT inhibitor perifosine, three cell lines showed a high or intermediate responsiveness to the drug while one cell line was resistant. The multikinase inhibitor regorafenib inhibited proliferation of all CRC lines with similar efficiency and independent of the presence or absence of KRAS, BRAF, PIK3CA, and TP53 mutations. Regorafenib action was associated with broad-range inhibitory effects at the level of gene expression but not with a general inhibition of AKT or MEK/ERK signaling. In vemurafenib-sensitive cells, the antiproliferative effect of vemurafenib was enhanced by the other SMI. Together, our results provide insights into the determinants of SMI efficiencies in CRC cells and encourage the further use of low-passage CRC cell lines as preclinical models.

  8. Biology and clinical implications of CD133+ liver cancer stem cells

    International Nuclear Information System (INIS)

    Hepatocellular carcinoma (HCC) is the most common primary malignant tumor of the liver, accounting for 80%–90% of all liver cancers. The disease ranks as the fifth most common cancer worldwide and is the third leading cause of all cancer-associated deaths. Although advances in HCC detection and treatment have increased the likelihood of a cure at early stages of the disease, HCC remains largely incurable because of late presentation and tumor recurrence. Only 25% of HCC patients are deemed suitable for curative treatment, with the overall survival at just a few months for inoperable patients. Apart from surgical resection, loco-regional ablation and liver transplantation, current treatment protocols include conventional cytotoxic chemotherapy. But due to the highly resistant nature of the disease, the efficacy of the latter regimen is limited. The recent emergence of the cancer stem cell (CSC) concept lends insight into the explanation of why treatment with chemotherapy often may seem to be initially successful but results in not only a failure to eradicate the tumor but also possibly tumor relapse. Commonly used anti-cancer drugs in HCC work by targeting the rapidly proliferating and differentiated liver cancer cells that constitute the bulk of the tumor. However, a subset of CSCs exists within the tumor, which are more resistant and are able to survive and maintain residence after treatment, thus, growing and self-renewing to generate the development and spread of recurrent tumors in HCC. In the past few years, compelling evidence has emerged in support of the hierarchic CSC model for solid tumors, including HCC. And in particular, CD133 has drawn significant attention as a critical liver CSC marker. Understanding the characteristics and function of CD133+ liver CSCs has also shed light on HCC management and treatment, including the implications for prognosis, prediction and treatment resistance. In this review, a detailed summary of the recent progress in CD

  9. Effects of 5-fluorouracil on biological characteristics and drug resistance mechanisms of liver cancer cell line PLC/RAF/5

    Directory of Open Access Journals (Sweden)

    CHENG Kangwen

    2015-09-01

    Full Text Available ObjectiveTo study the changes in biological characteristics of a liver cancer cell line PLC/RAF/5 after repeated exposure to a chemotherapy drug, 5-fluorouraci (5-FU, and to investigate the relationship between drug-resistant liver cancer cells and liver cancer stem cells. MethodsA low concentration of 5-FU (1 μg/ml was used to treat the human liver cancer cell line PLC/RAF/5 repeatedly to establish the PLC/RAF/5/5-FU cell line. Morphological differences between the two types of cells were observed. The inhibitory effects of different concentrations of 5-FU (0, 0.25, 0.5, 1, 1.5, and 2 μg/ml on the proliferation of the two types of cells were determined using the CCK-8 assay. Apoptosis of the two types of cells after exposure to different concentrations of 5-FU (0.5, 1, and 2 μg/ml for 48 h was analyzed using flow cytometry. The proportions of side population cells in both types of cells were measured using flow cytometry. The colony-forming ability was compared between the two types of cells by the plate colony-forming assay. The expression of Bax, Bcl-2, ABCG2, and FoxM1 proteins in both types of cells was examined by Western blot. Between-group comparison was performed by t test. ResultsThe PLC/RAF/5/5-FU cell line was successfully established using the chemotherapy drug 5-FU. Compared with the PLC/RAF/5 cells, the PLC/RAF/5/5-FU cells had a larger volume, fewer protrusions, a changed shape of a long shuttle, and enhanced refractivity. Moreover, compared with the parent cells, the PLC/RAF/5/5-FU cells had a significantly lower sensitivity to the inhibitory effect of 5-FU on proliferation, a significantly lower proportion of cells at the G0/G1 phase of the cell cycle, significantly higher proportions of cells at the S and G2/M phases, significantly higher resistance to apoptosis, a significantly higher proportion of side population cells, and significantly enhanced proliferation (P<0.05. According to the results of Western blot assay, the

  10. Biology and clinical implications of CD133{sup +} liver cancer stem cells

    Energy Technology Data Exchange (ETDEWEB)

    Ma, Stephanie, E-mail: stefma@hku.hk [Department of Clinical Oncology, State Key Laboratory for Liver Research, LKS Faculty of Medicine, The University of Hong Kong (Hong Kong)

    2013-01-15

    Hepatocellular carcinoma (HCC) is the most common primary malignant tumor of the liver, accounting for 80%–90% of all liver cancers. The disease ranks as the fifth most common cancer worldwide and is the third leading cause of all cancer-associated deaths. Although advances in HCC detection and treatment have increased the likelihood of a cure at early stages of the disease, HCC remains largely incurable because of late presentation and tumor recurrence. Only 25% of HCC patients are deemed suitable for curative treatment, with the overall survival at just a few months for inoperable patients. Apart from surgical resection, loco-regional ablation and liver transplantation, current treatment protocols include conventional cytotoxic chemotherapy. But due to the highly resistant nature of the disease, the efficacy of the latter regimen is limited. The recent emergence of the cancer stem cell (CSC) concept lends insight into the explanation of why treatment with chemotherapy often may seem to be initially successful but results in not only a failure to eradicate the tumor but also possibly tumor relapse. Commonly used anti-cancer drugs in HCC work by targeting the rapidly proliferating and differentiated liver cancer cells that constitute the bulk of the tumor. However, a subset of CSCs exists within the tumor, which are more resistant and are able to survive and maintain residence after treatment, thus, growing and self-renewing to generate the development and spread of recurrent tumors in HCC. In the past few years, compelling evidence has emerged in support of the hierarchic CSC model for solid tumors, including HCC. And in particular, CD133 has drawn significant attention as a critical liver CSC marker. Understanding the characteristics and function of CD133{sup +} liver CSCs has also shed light on HCC management and treatment, including the implications for prognosis, prediction and treatment resistance. In this review, a detailed summary of the recent progress

  11. Synthesis and biological evaluation of retinoid-chalcones as inhibitors of colon cancer cell growth

    OpenAIRE

    Mizuno, Cassia S.; Paul, Shiby; Suh, Nanjoo; Rimando, Agnes M.

    2010-01-01

    Based on the observed anticancer activity of chalcones and retinoids, a novel class of retinoid-chalcone hybrids was designed and synthesized. As part of our ongoing studies to discover natural product based anticancer compounds, the retinoid-chalcone hybrids were tested against the colon cancer cell line HT-29. Retinoid like moiety was introduced through Friedel-Crafts alkylation of toluene. Among the synthesized compounds, the cyano derivative (E)-3-(3-oxo-3-(3,5,5,8,8-pentamethyl-5,6,7,8-t...

  12. Skin Cancer: Biology, Risk Factors & Treatment

    Science.gov (United States)

    ... turn Javascript on. Feature: Skin Cancer Skin Cancer: Biology, Risk Factors & Treatment Past Issues / Summer 2013 Table ... Articles Skin Cancer Can Strike Anyone / Skin Cancer: Biology, Risk Factors & Treatment / Timely Healthcare Checkup Catches Melanoma ...

  13. The amphiphilic nature of saponins and their effects on artificial and biological membranes and potential consequences for red blood and cancer cells

    OpenAIRE

    Lorent, Joseph H.; Quetin-Leclercq, Joëlle; Mingeot-Leclercq, Marie-Paule

    2014-01-01

    Saponins, amphiphiles of natural origin with numerous biological activities, are widely used in the cosmetic and pharmaceutical industry. Some saponins exhibit relatively selective cytotoxic effects on cancer cells but the tendency of saponins to induce hemolysis limits their anticancer potential. This review focused on the effects of saponin activity on membranes and consequent implications for red blood and cancer cells. This activity seems to be strongly related to the amphiphilic characte...

  14. Metabolites of ginger component [6]-shogaol remain bioactive in cancer cells and have low toxicity in normal cells: chemical synthesis and biological evaluation.

    Directory of Open Access Journals (Sweden)

    Yingdong Zhu

    Full Text Available Our previous study found that [6]-shogaol, a major bioactive component in ginger, is extensively metabolized in cancer cells and in mice. It is unclear whether these metabolites retain bioactivity. The aim of the current study is to synthesize the major metabolites of [6]-shogaol and evaluate their inhibition of growth and induction of apoptosis in human cancer cells. Twelve metabolites of [6]-shogaol (M1, M2, and M4-M13 were successfully synthesized using simple and easily accessible chemical methods. Growth inhibition assays showed that most metabolites of [6]-shogaol had measurable activities against human cancer cells HCT-116 and H-1299. In particular, metabolite M2 greatly retained the biological activities of [6]-shogaol, with an IC(50 of 24.43 µM in HCT-116 human colon cancer cells and an IC(50 of 25.82 µM in H-1299 human lung cancer cells. Also exhibiting a relatively high potency was thiol-conjugate M13, with IC(50 values of 45.47 and 47.77 µM toward HCT-116 and H-1299 cells, respectively. The toxicity evaluation of the synthetic metabolites (M1, M2, and M4-M13 against human normal fibroblast colon cells CCD-18Co and human normal lung cells IMR-90 demonstrated a detoxifying metabolic biotransformation of [6]-shogaol. The most active metabolite M2 had almost no toxicity to CCD-18Co and IMR-90 normal cells with IC(50s of 99.18 and 98.30 µM, respectively. TUNEL (Terminal deoxynucleotidyl transferase dUTP nick end labeling assay indicated that apoptosis was triggered by metabolites M2, M13, and its two diastereomers M13-1 and M13-2. There was no significant difference between the apoptotic effect of [6]-shogaol and the effect of M2 and M13 after 6 hour treatment.

  15. Metabolites of ginger component [6]-shogaol remain bioactive in cancer cells and have low toxicity in normal cells: chemical synthesis and biological evaluation.

    Science.gov (United States)

    Zhu, Yingdong; Warin, Renaud F; Soroka, Dominique N; Chen, Huadong; Sang, Shengmin

    2013-01-01

    Our previous study found that [6]-shogaol, a major bioactive component in ginger, is extensively metabolized in cancer cells and in mice. It is unclear whether these metabolites retain bioactivity. The aim of the current study is to synthesize the major metabolites of [6]-shogaol and evaluate their inhibition of growth and induction of apoptosis in human cancer cells. Twelve metabolites of [6]-shogaol (M1, M2, and M4-M13) were successfully synthesized using simple and easily accessible chemical methods. Growth inhibition assays showed that most metabolites of [6]-shogaol had measurable activities against human cancer cells HCT-116 and H-1299. In particular, metabolite M2 greatly retained the biological activities of [6]-shogaol, with an IC(50) of 24.43 µM in HCT-116 human colon cancer cells and an IC(50) of 25.82 µM in H-1299 human lung cancer cells. Also exhibiting a relatively high potency was thiol-conjugate M13, with IC(50) values of 45.47 and 47.77 µM toward HCT-116 and H-1299 cells, respectively. The toxicity evaluation of the synthetic metabolites (M1, M2, and M4-M13) against human normal fibroblast colon cells CCD-18Co and human normal lung cells IMR-90 demonstrated a detoxifying metabolic biotransformation of [6]-shogaol. The most active metabolite M2 had almost no toxicity to CCD-18Co and IMR-90 normal cells with IC(50)s of 99.18 and 98.30 µM, respectively. TUNEL (Terminal deoxynucleotidyl transferase dUTP nick end labeling) assay indicated that apoptosis was triggered by metabolites M2, M13, and its two diastereomers M13-1 and M13-2. There was no significant difference between the apoptotic effect of [6]-shogaol and the effect of M2 and M13 after 6 hour treatment. PMID:23382939

  16. ZNF217 expression correlates with the biological behavior of human ovarian cancer cells

    Institute of Scientific and Technical Information of China (English)

    Lilin Hang; Min Zhang; Fanliang Meng; Mei Zhong; Jing Li 

    2014-01-01

    Objective:The aim of the study was to investigate the correlation of zinc-finger protein 217 (ZNF217) gene ex-pression with the biological behavior of human ovarian cancer HO-8910 cel s. Methods:The expression of ZNF217 in ovarian carcinoma cel lines was detected by RT-PCR and Western blot, respectively. The biological behaviors of the transfectants were investigated by MTT, in vitro Boyden chamber and in vivo invasion assay, respectively. Results:RT-PCR and Western blotting revealed that transfection of ZNF217 into the HO-8910 cel s significantly increased their proliferation along with mark-edly enhanced in vitro and in vivo invasion and metastatic abilities. MTT assay showed that the proliferation ability of pEGFP-N1-ZNF217/HO-8910 cel s was significantly higher than that of pEGFP-N1/HO-8910 cel s and HO-8910 cel s (P<0.001). The Boyden chamber assay showed that the numbers of migrating pEGFP-N1-ZNF217/HO-8910, pEGFP-N1/HO-8910 and HO-8910 cel s were (141.25 ± 13.91) cel s/200 × field, (82.50 ± 11.73) cel s/200 × field and (81.75 ± 12.12) cel s/200 × field, respectively, with a significant dif erence between them (F=29.274, P<0.001). The nude mouse experiment showed that the in vivo tumor formation ability of pEGFP-N1-ZNF217/HO-8910 cel s was significantly higher than that of pEGFP-N1/HO-8910 cel s (P<0.001). Conclusion:Based on these clinical and laboratory observations, we conclude that ZNF217 may contribute to ovarian cancer invasion and metastasis, and associated with worse clinical outcomes. We evaluated ZNF217’s role as a biomarker of ovarian carcinogenesis and tumor progression in patient samples and explored possible molecular mechanisms in promoting tumor growth and invasion.

  17. Cancer Stem Cells in Breast Cancer

    OpenAIRE

    Fumitaka Takeshita; Tomohiro Fujiwara; Takahiro Ochiya; Makiko Ono; Ryou-u Takahashi

    2011-01-01

    The cancer stem cell (CSC) theory is generally acknowledged as an important field of cancer research, not only as an academic matter but also as a crucial aspect of clinical practice. CSCs share a variety of biological properties with normal somatic stem cells in self-renewal, the propagation of differentiated progeny, the expression of specific cell markers and stem cell genes, and the utilization of common signaling pathways and the stem cell niche. However, CSCs differ from normal stem cel...

  18. Biological activity of ruthenium and osmium arene complexes with modified paullones in human cancer cells.

    Science.gov (United States)

    Mühlgassner, Gerhard; Bartel, Caroline; Schmid, Wolfgang F; Jakupec, Michael A; Arion, Vladimir B; Keppler, Bernhard K

    2012-11-01

    In an attempt to combine the ability of indolobenzazepines (paullones) to inhibit cyclin-dependent kinases (Cdks) and that of platinum-group metal ions to interact with proteins and DNA, ruthenium(II) and osmium(II) arene complexes with paullones were prepared, expecting synergies and an increase of solubility of paullones. Complexes with the general formula [M(II)Cl(η(6)-p-cymene)L]Cl, where M=Ru (1, 3) or Os (2, 4), and L=L(1) (1, 2) or L(2) (3, 4), L(1)=N-(9-bromo-7,12-dihydroindolo[3,2-d][1]-benzazepin-6(5H)-yliden-N'-(2-hydroxybenzylidene)azine and L(2)=N-(9-bromo-7,12-dihydroindolo[3,2-d][1]benzazepin-6-yl)-N'-[3-hydroxy-5-(hydroxymethyl)-2-methylpyridin-4-yl-methylene]azinium chloride (L(2)(*)HCl), were now investigated regarding cytotoxicity and accumulation in cancer cells, impact on the cell cycle, capacity of inhibiting DNA synthesis and inducing apoptosis as well as their ability to inhibit Cdk activity. The MTT (3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide) assay yielded IC(50) values in the nanomolar to low micromolar range. In accordance with cytotoxicity data, the BrdU assay showed that 1 is the most and 4 the least effective of these compounds regarding inhibition of DNA synthesis. Effects on the cell cycle are minor, although concentration-dependent inhibition of Cdk2/cyclin E activity was observed in cell-free experiments. Induction of apoptosis is most pronounced for complex 1, accompanied by a low fraction of necrotic cells, as observed by annexin V-fluorescein isothiocyanate/propidium iodide staining and flow cytometric analysis. PMID:23037896

  19. Omics/systems biology and cancer cachexia.

    Science.gov (United States)

    Gallagher, Iain J; Jacobi, Carsten; Tardif, Nicolas; Rooyackers, Olav; Fearon, Kenneth

    2016-06-01

    Cancer cachexia is a complex syndrome generated by interaction between the host and tumour cells with a background of treatment effects and toxicity. The complexity of the physiological pathways likely involved in cancer cachexia necessitates a holistic view of the relevant biology. Emergent properties are characteristic of complex systems with the result that the end result is more than the sum of its parts. Recognition of the importance of emergent properties in biology led to the concept of systems biology wherein a holistic approach is taken to the biology at hand. Systems biology approaches will therefore play an important role in work to uncover key mechanisms with therapeutic potential in cancer cachexia. The 'omics' technologies provide a global view of biological systems. Genomics, transcriptomics, proteomics, lipidomics and metabolomics approaches all have application in the study of cancer cachexia to generate systems level models of the behaviour of this syndrome. The current work reviews recent applications of these technologies to muscle atrophy in general and cancer cachexia in particular with a view to progress towards integration of these approaches to better understand the pathology and potential treatment pathways in cancer cachexia. PMID:26783720

  20. The clinical significance of Psoriasin for non-small cell lung cancer patients and its biological impact on lung cancer cell functions

    International Nuclear Information System (INIS)

    Psoriasin (S100A7) is a member of the S100 gene family. Alteration of Psoriasin expression has previously been reported to play an important role in cancer aggressive behaviour. The current study sought to investigate the level of Psoriasin expression at the mRNA level in a cohort of patients with non-small cell lung cancer (NSCLC), the association with clinical implication and outcomes, and the molecular and cellular impact of the protein on lung cancer cells. Fresh frozen NSCLC cell carcinoma tissues, along with matched normal tissues were obtained from 83 NSCLC patients who received curative resection from January 2003 to December 2011. The expression of Psoriasin in the NSCLC specimens was assessed using both quantitative real time PCR (QPCR) and immunochemical staining. Knockdown and forced expression of Psoriasin in NSCLC cell lines were carried out using constructed plasmid vectors carrying either ribozyme transgenes targeting human Psoriasin or full-length coding sequence, respectively. The effect of Psoriasin on the functions of NSCLC cells was determined using a variety of in vitro cell function assays. Higher mRNA levels of Psoriasin were observed in tumour tissues when compared to both the paired normal background tissues and none paired normal tissues (p = 0.0251 and 0.0195). The mRNA level of Psoriasin was found to be higher in the squamous carcinoma (P=0.035). Higher Psoriasin expression is associated with poor prognosis. The cell function tests had supportive results to the clinical findings. Over-expression of Posriasin in lung cancer cells (SK-MES-1) resulted in an increase in in vitro growth and invasiveness. In contrast, Psoriasin knockdown suppressed cell growth and invasion (P<0.05), but increased cell adhesion (P<0.05). Psoriasin expression is increased in lung cancer, more specifically in lung squamous carcinoma compared with adenocarcinoma, and is associated with poor prognosis. Psoriasin plays crucial roles in regulating the growth and

  1. Lung Cancer Cell Line Screen Links Fanconi Anemia/BRCA Pathway Defects to Increased Relative Biological Effectiveness of Proton Radiation

    Energy Technology Data Exchange (ETDEWEB)

    Liu, Qi; Ghosh, Priyanjali; Magpayo, Nicole [Laboratory of Cellular and Molecular Radiation Oncology, Massachusetts General Hospital, Boston, Massachusetts (United States); Testa, Mauro; Tang, Shikui [Division of Radiation Physics, Department of Radiation Oncology, Massachusetts General Hospital, Boston, Massachusetts (United States); Gheorghiu, Liliana [Laboratory of Cellular and Molecular Radiation Oncology, Massachusetts General Hospital, Boston, Massachusetts (United States); Biggs, Peter; Paganetti, Harald [Division of Radiation Physics, Department of Radiation Oncology, Massachusetts General Hospital, Boston, Massachusetts (United States); Efstathiou, Jason A. [Laboratory of Cellular and Molecular Radiation Oncology, Massachusetts General Hospital, Boston, Massachusetts (United States); Lu, Hsiao-Ming [Division of Radiation Physics, Department of Radiation Oncology, Massachusetts General Hospital, Boston, Massachusetts (United States); Held, Kathryn D. [Laboratory of Cellular and Molecular Radiation Oncology, Massachusetts General Hospital, Boston, Massachusetts (United States); Willers, Henning, E-mail: hwillers@mgh.harvard.edu [Laboratory of Cellular and Molecular Radiation Oncology, Massachusetts General Hospital, Boston, Massachusetts (United States)

    2015-04-01

    Purpose: Growing knowledge of genomic heterogeneity in cancer, especially when it results in altered DNA damage responses, requires re-examination of the generic relative biological effectiveness (RBE) of 1.1 of protons. Methods and Materials: For determination of cellular radiosensitivity, we irradiated 17 lung cancer cell lines at the mid-spread-out Bragg peak of a clinical proton beam (linear energy transfer, 2.5 keV/μm). For comparison, 250-kVp X rays and {sup 137}Cs γ-rays were used. To estimate the RBE of protons relative to {sup 60}Co (Co60eq), we assigned an RBE(Co60Eq) of 1.1 to X rays to correct the physical dose measured. Standard DNA repair foci assays were used to monitor damage responses. FANCD2 was depleted using RNA interference. Results: Five lung cancer cell lines (29.4%) exhibited reduced clonogenic survival after proton irradiation compared with X-irradiation with the same physical doses. This was confirmed in a 3-dimensional sphere assay. Corresponding proton RBE(Co60Eq) estimates were statistically significantly different from 1.1 (P≤.05): 1.31 to 1.77 (for a survival fraction of 0.5). In 3 of these lines, increased RBE was correlated with alterations in the Fanconi anemia (FA)/BRCA pathway of DNA repair. In Calu-6 cells, the data pointed toward an FA pathway defect, leading to a previously unreported persistence of proton-induced RAD51 foci. The FA/BRCA-defective cells displayed a 25% increase in the size of subnuclear 53BP1 foci 18 hours after proton irradiation. Conclusions: Our cell line screen has revealed variations in proton RBE that are partly due to FA/BRCA pathway defects, suggesting that the use of a generic RBE for cancers should be revisited. We propose that functional biomarkers, such as size of residual 53BP1 foci, may be used to identify cancers with increased sensitivity to proton radiation.

  2. Lung Cancer Cell Line Screen Links Fanconi Anemia/BRCA Pathway Defects to Increased Relative Biological Effectiveness of Proton Radiation

    International Nuclear Information System (INIS)

    Purpose: Growing knowledge of genomic heterogeneity in cancer, especially when it results in altered DNA damage responses, requires re-examination of the generic relative biological effectiveness (RBE) of 1.1 of protons. Methods and Materials: For determination of cellular radiosensitivity, we irradiated 17 lung cancer cell lines at the mid-spread-out Bragg peak of a clinical proton beam (linear energy transfer, 2.5 keV/μm). For comparison, 250-kVp X rays and 137Cs γ-rays were used. To estimate the RBE of protons relative to 60Co (Co60eq), we assigned an RBE(Co60Eq) of 1.1 to X rays to correct the physical dose measured. Standard DNA repair foci assays were used to monitor damage responses. FANCD2 was depleted using RNA interference. Results: Five lung cancer cell lines (29.4%) exhibited reduced clonogenic survival after proton irradiation compared with X-irradiation with the same physical doses. This was confirmed in a 3-dimensional sphere assay. Corresponding proton RBE(Co60Eq) estimates were statistically significantly different from 1.1 (P≤.05): 1.31 to 1.77 (for a survival fraction of 0.5). In 3 of these lines, increased RBE was correlated with alterations in the Fanconi anemia (FA)/BRCA pathway of DNA repair. In Calu-6 cells, the data pointed toward an FA pathway defect, leading to a previously unreported persistence of proton-induced RAD51 foci. The FA/BRCA-defective cells displayed a 25% increase in the size of subnuclear 53BP1 foci 18 hours after proton irradiation. Conclusions: Our cell line screen has revealed variations in proton RBE that are partly due to FA/BRCA pathway defects, suggesting that the use of a generic RBE for cancers should be revisited. We propose that functional biomarkers, such as size of residual 53BP1 foci, may be used to identify cancers with increased sensitivity to proton radiation

  3. Mammalian cell biology

    International Nuclear Information System (INIS)

    This section contains summaries of research on mechanisms of lethality and radioinduced changes in mammalian cell properties, new cell systems for the study of the biology of mutation and neoplastic transformation, and comparative properties of ionizing radiations

  4. Biological functions of decorin in cancer

    Institute of Scientific and Technical Information of China (English)

    Xiu-Li Bi; Wancai Yang

    2013-01-01

    Decorin is a member of the extracellular matrix small leucine-rich proteoglycans family that exists and functions in stromal and epithelial cells.Accumulating evidence suggests that decorin affects the biology of various types of cancer by directly or indirectly targeting the signaling molecules involved in cell growth,survival,metastasis,and angiogenesis.More recent studies show that decorin plays important roles during tumor development and progression and is a potential cancer therapeutic agent.In this article,we summarize recent studies of decorin in cancer and discuss decorin's therapeutic and prognostic value.

  5. The different biological effects of single, fractioned and continuous low dose rate radiation on CL187 colorectal cancer cell line

    International Nuclear Information System (INIS)

    Objective: To investigate the effect and underlying mechanism of single, fractioned and continuous low dose rate radiation on CL187 colorectal cancer cell line. Methods: CL187 cells were exposed to 6 MV X-rays at a high dose rate of 4 Gy/min and 125I seed at a low dose rate of 2.77 cGy/h with three groups:single dose radiation group (SDR), fractioned dose radiation group (FDR) by 2 Gy/f, and continuous low dose rate radiation group (CLDR). The radiation doses were 0, 2, 4 and 8 Gy. Total cell number and cell viability were determined by trypan blue. Clone forming assay was used to evaluate the cell proliferation ability. The percentage of apoptosis cells was analyzed by flow cytometry. Western blot was used to detect the protein expression levels of PHLPP2, PTEN and Bax. Results: Compared with SDR and FDR groups, the total cell number and survival fraction of CLDR group decreased. The relative biological effect (RBE) for 125I seeds compared with 6 MV X-rays was 1.41. The percentage of apoptosis cells of CLDR group was significantly increased (t=-15.08, -11.99, P<0.05). The expression level of Bax increased in CLDR group, while no obvious changes were observed on PHLPP2 and PTEN among three groups. Conclusions: The expression level of PHLPP2 increases in SDR, FDR and CLDR group, while it seems that it was not influenced by dose rate. The expression level of Bax increased in three groups, while more colorectal CL187 cells in CLDR group may be killed due to the increase of Bax expression. (authors)

  6. Dendritic cell vaccines in cancer immunotherapy: from biology to translational medicine

    Institute of Scientific and Technical Information of China (English)

    Hongmei Xu; Xuetao Cao

    2011-01-01

    According to the GLOBOCAN reports,there were about 12.7 million cancer cases and 7.6 million cancer deaths in 2008,and the cancer burden continues to increase worldwide [1].At present,the common treatments for cancer include surgery,chemotherapy,radiotherapy,and immunotherapy.Immunotherapy aims to enhance or regulate the patient's own immune response to fight against tumors.It represents a novel and effective strategy in cancer treatments,but,generally,its efficacy needs to be improved [2].Cancer vaccination is an important and promising approach in cancer immunotherapy.For many years,prophylactic vaccines have exhibited profound accomplishment in preventing serious infectious diseases in humankind,including polio,small pox,and diphtheria.However,cancer vaccines are vastly different from the prophylactic vaccines in that they are aimed to eliminate preexisting tumors.Furthermore,the immune system is immunosuppressed in most cancer patients,so it is much more difficult to develop effective cancer vaccines.

  7. Biological heterogeneity of cancer

    OpenAIRE

    Isaiah J. Fidler

    2012-01-01

    Despite significant improvements in diagnosis, surgical techniques, and advancements in general patient care, the majority of deaths from cancer are caused by the continuous growth of metastases that are resistant to conventional therapies. In a large number of cancer patients, metastasis may well have occurred by the time of diagnosis. The metastases can be located in different distant organs and in different regions within a single organ. The major obstacle for the eradication of metastases...

  8. Cancer biology in diabetes

    OpenAIRE

    Sen, Shi; He, Yanzheng; Koya, Daisuke; Kanasaki, Keizo

    2014-01-01

    Abstract Diabetes is a serious metabolic disease that causes multiple organ dysfunctions. Recent evidence suggests that diabetes could contribute to the initiation and progression of certain cancers in addition to the classic diabetic complications. Furthermore, some of the drugs used clinically to treat patients with diabetes might affect cancer initiation, progression and mortality. The recent discovery of the possible anticancer effects of metformin, a classic antidiabetic drug, has led ph...

  9. The different biological effects of single, fractionated and continuous low dose rate irradiation on CL187 colorectal cancer cells

    International Nuclear Information System (INIS)

    To determine the biological effectiveness of single, fractionated and continuous low dose rate irradiation on the human colorectal cancer cell line CL187 in vitro and explore the cellular mechanisms. The CL187 cells were exposed to radiation of 6 MV X-ray at a high dose rate of 4Gy/min and 125I seed at a low dose rate of 2.77 cGy/h. Three groups were employed: single dose radiation group (SDR), fractionated dose radiation group (FDR) by 2Gy/f and continuous low dose rate radiation group (CLDR). Four radiation doses 2, 4, 6 and 8Gy were chosen and cells without irradiation as the control. The responses of CL187 cells to distinct modes of radiation were evaluated by the colony-forming assay, cell cycle progression as well as apoptosis analysis. In addition, we detected the expression patterns of DNA-PKcs, Ku70 and Ku80 by Western blotting. The relative biological effect for 125I seeds compared with 6 MV X-ray was 1.42. 48 hrs after 4Gy irradiation, the difference between proportions of cells at G2/M phase of SDR and CLDR groups were statistically significant (p = 0.026), so as the FDR and CLDR groups (p = 0.005). 48 hrs after 4Gy irradiation, the early apoptotic rate of CLDR group was remarkably higher than SDR and FDR groups (CLDR vs. SDR, p = 0.001; CLDR vs. FDR, p = 0.02), whereas the late apoptotic rate of CLDR group increased significantly compared with SDR and FDR group (CLDR vs. SDR, p = 0.004; CLDR vs. FDR, p = 0.007). Moreover, DNA-PKcs and Ku70 expression levels in CLDR-treated cells decreased compared with SDR and FDR groups. Compared with the X-ray high dose rate irradiation, 125I seeds CLDR showed more effective induction of cell apoptosis and G2/M cell cycle arrest. Furthermore, 125I seeds CLDR could impair the DNA repair capability by down-regulating DNA-PKcs and Ku70 expression

  10. Stem Cells and Cancer

    International Nuclear Information System (INIS)

    Stem cell research has thrived over the last years due to their therapeutic and regenerative potential. Scientific breakthroughs in the field are immediately translated from the scientific journals to the mass media, which is not surprising as the characterisation of the molecular mechanisms that regulate the biology of stem cells is crucial for the treatment of degenerative and cardiovascular diseases, as well as cancer. In the Molecular Oncology Unit at Ciemat we work to unravel the role of cancer stem cells in tumour development, and to find new antitumor therapies. (Author)

  11. Lung cancer - small cell

    Science.gov (United States)

    Cancer - lung - small cell; Small cell lung cancer; SCLC ... About 15% of all lung cancer cases are SCLC. Small cell lung cancer is slightly more common in men than women. Almost all cases of SCLC ...

  12. Lung cancer - small cell

    Science.gov (United States)

    Cancer - lung - small cell; Small cell lung cancer; SCLC ... About 15% of all lung cancer cases are SCLC. Small cell lung cancer is slightly more common in men than women. Almost all cases of SCLC are ...

  13. Synthetic and Biological Studies of Sesquiterpene Polygodial: Activity of 9-Epipolygodial against Drug-Resistant Cancer Cells.

    Science.gov (United States)

    Dasari, Ramesh; De Carvalho, Annelise; Medellin, Derek C; Middleton, Kelsey N; Hague, Frédéric; Volmar, Marie N M; Frolova, Liliya V; Rossato, Mateus F; De La Chapa, Jorge J; Dybdal-Hargreaves, Nicholas F; Pillai, Akshita; Mathieu, Véronique; Rogelj, Snezna; Gonzales, Cara B; Calixto, João B; Evidente, Antonio; Gautier, Mathieu; Munirathinam, Gnanasekar; Glass, Rainer; Burth, Patricia; Pelly, Stephen C; van Otterlo, Willem A L; Kiss, Robert; Kornienko, Alexander

    2015-12-01

    Polygodial, a terpenoid dialdehyde isolated from Polygonum hydropiper L., is a known agonist of the transient receptor potential vanilloid 1 (TRPV1). In this investigation a series of polygodial analogues were prepared and investigated for TRPV1-agonist and anticancer activities. These experiments led to the identification of 9-epipolygodial, which has antiproliferative potency significantly exceeding that of polygodial. 9-Epipolygodial was found to maintain potency against apoptosis-resistant cancer cells as well as those displaying the multidrug-resistant (MDR) phenotype. In addition, the chemical feasibility for the previously proposed mechanism of action of polygodial, involving the formation of a Paal-Knorr pyrrole with a lysine residue on the target protein, was demonstrated by the synthesis of a stable polygodial pyrrole derivative. These studies reveal rich chemical and biological properties associated with polygodial and its direct derivatives. These compounds should inspire further work in this area aimed at the development of new pharmacological agents, or the exploration of novel mechanisms of covalent modification of biological molecules with natural products. PMID:26434977

  14. Molecular biology of the lung cancer

    International Nuclear Information System (INIS)

    Background. Lung cancer is one of the most common malignant diseases and leading cause of cancer death worldwide. The advances in molecular biology and genetics, including the modern microarray technology and rapid sequencing techniques, have enabled a remarkable progress into elucidating the lung cancer ethiopathogenesis. Numerous studies suggest that more than 20 different genetic and epigenetic alterations are accumulating during the pathogenesis of clinically evident pulmonary cancers as a clonal, multistep process. Thus far, the most investigated alterations are the inactivational mutations and losses of tumour suppressor genes and the overexpression of growth-promoting oncogenes. More recently, the acquired epigenetic inactivation of tumour suppressor genes by promoter hypermethylation has been recognized. The early clonal genetic abnormalities that occur in preneoplastic bronchial epithelium damaged by smoking or other carcinogenes are being identified. The molecular distinctions between small cell lung cancer (SCLC) and non-small cell lung cancer (NSCLC), as well as between tumors with different clinical outcomes have been described. These investigations lead to the hallmarks of lung cancer. Conclusions. It is realistic to expect that the molecular and cell culture-based investigations will lead to discoveries of new clinical applications with the potential to provide new avenues for early diagnosis, risk assessment, prevention, and most important, new more effective treatment approaches for the lung cancer patients. (author)

  15. Molecular control of the cell cycle in cancer: biological and clinical aspects

    DEFF Research Database (Denmark)

    Møller, Michael Boe

    2003-01-01

    The RB1 pathway and the p53 pathway represent important, interconnected biochemical units frequently perturbed in human cancer. Essential tumor protective mechanisms, such as cellular growth control and apoptosis, are regulated through these systems. Comprehensive studies of these pathways, inclu...

  16. Synthesis and Biological Evaluation of Retinoid-Chalcones as Inhibitors of Colon Cancer Cell Growth

    Science.gov (United States)

    Based on the observed anticancer activity of chalcones and retinoids, a novel class of retinoid-chalcone hybrids were designed and synthesized. As part of our ongoing studies to discover natural product based anticancer compounds, the retinoid-chalcone hybrids were tested against the colon cancer ce...

  17. Cell Biology and Cancer. Grades 9-12. NIH Curriculum Supplement Series.

    Science.gov (United States)

    Biological Sciences Curriculum Study, Colorado Springs.

    This curriculum supplement guide brings the latest medical discoveries to classrooms. This module focuses on the objectives of introducing students to major concepts related to the development of cancer and its impacts, and developing an understanding of the relationship between biomedical research and personal and public health. This module…

  18. Deciphering cancer heterogeneity: the biological space

    Directory of Open Access Journals (Sweden)

    XinWeiWang

    2014-04-01

    Full Text Available Most lethal solid tumors including hepatocellular carcinoma (HCC are considered incurable due to extensive heterogeneity in clinical presentation and tumor biology. Tumor heterogeneity may result from different cells of origin, patient ethnicity, etiology, underlying disease and diversity of genomic and epigenomic changes which drive tumor development. Cancer genomic heterogeneity thereby impedes treatment options and poses a significant challenge to cancer management. Studies of the HCC genome have revealed that although various genomic signatures identified in different HCC subgroups share a common prognosis, each carries unique molecular changes which are linked to different sets of cancer hallmarks whose misregulation has been proposed by Hanahan and Weinberg to be essential for tumorigenesis. We hypothesize that these specific sets of cancer hallmarks collectively occupy different tumor biological space representing the misregulation of different biological processes. In principle, a combination of different cancer hallmarks can result in new convergent molecular networks that are unique to each tumor subgroup and represent ideal druggable targets. Due to the ability of the tumor to adapt to external factors such as treatment or changes in the tumor microenvironment, the tumor biological space is elastic. Our ability to identify distinct groups of cancer patients with similar tumor biology who are most likely to respond to a specific therapy would have a significant impact on improving patient outcome. It is currently a challenge to identify a particular hallmark or a newly emerged convergent molecular network for a particular tumor. Thus, it is anticipated that the integration of multiple levels of data such as genomic mutations, somatic copy number aberration, gene expression, proteomics, and metabolomics, may help us grasp the tumor biological space occupied by each individual, leading to improved therapeutic intervention and outcome.

  19. Targeting beta III-tubulin in glioblastoma multiforme: from cell biology and histopathology to cancer therapeutics

    Czech Academy of Sciences Publication Activity Database

    Katsetos, C.D.; Dráber, Pavel; Kavallaris, M.

    2011-01-01

    Roč. 11, č. 8 (2011), s. 719-728. ISSN 1871-5206 R&D Projects: GA ČR GAP302/10/1759 Institutional research plan: CEZ:AV0Z50520514 Keywords : glioblastoma multiforme * tubulin binding agent * epothilones Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 2.862, year: 2011

  20. Molecular Biology of Esophageal Cancer

    Institute of Scientific and Technical Information of China (English)

    HuanXi; JanBrabender; RalfMetzger; PaulM.Schneider

    2004-01-01

    There have been many new developments in our understanding of esophageal carcinoma biology over the past several years. Information regarding both of the major forms of this disease, adenocarcinoma and squamous cell carcinoma, has accumulated in conjunction with data on precursor conditions such as Barrett's esophagus. Interesting and promising findings have included overexpression of proto-oncogenes,loss of heterozygosity at multiple chromosomal loci, tumor suppressor gene inactivation, epigenetic silencing by DNA methylation, and mutations and deletions involving the tumor suppressor gene p53. Important cancer pathways, the cyclin kinase inhibitor cascade and the DNA mismatch repair process, implicated in the genesis of multiple tumor types have also been inculpated in esophageal carcinogenesis. Alterations in the p16 and p15 cyclin kinase inhibitors including point mutations and homozygous deletions have been reported in primary esophageal tumors. Further developments in the field of molecular carcinogenesis of esophageal malignancies promise to yield improvements in prevention, early detection, prognostic categorization, and perhaps gene-based therapy of this deadly disease.

  1. Lung Stem cell biology

    OpenAIRE

    Ardhanareeswaran, Karthikeyan; Mirotsou, Maria

    2013-01-01

    Over the past few years new insights have been added to the study of stem cells in the adult lung. The exploration of the endogenous lung progenitors as well as the study of exogenously delivered stem cell populations holds promise for advancing our understanding of the biology of lung repair mechanisms. Moreover, it opens new possibilities for the use of stem cell therapy for the development of regenerative medicine approaches for the treatment of lung disease. Here, we discuss the main type...

  2. The MUC1 oncomucin regulates pancreatic cancer cell biological properties and chemoresistance. Implication of p42–44 MAPK, Akt, Bcl-2 and MMP13 pathways

    Energy Technology Data Exchange (ETDEWEB)

    Tréhoux, Solange; Duchêne, Bélinda; Jonckheere, Nicolas; Van Seuningen, Isabelle, E-mail: isabelle.vanseuningen@inserm.fr

    2015-01-16

    Highlights: • Loss of MUC1 decreases proliferation and tumor growth via β-catenin and p42–44 MAPK. • Inhibition of MUC1 decreases cell migration and invasion through MMP13. • Loss of MUC1 decreases survival and increases apoptosis via Akt and Bcl-2 pathways. • Loss of MUC1 sensitizes cells to gemcitabine and 5-Fluorouracil chemotherapeutic drugs. - Abstract: MUC1 is an oncogenic mucin overexpressed in several epithelial cancers, including pancreatic ductal adenocarcinoma, and is considered as a potent target for cancer therapy. To this aim, we undertook to study MUC1 biological effects on pancreatic cancer cells and identify pathways mediating these effects. Our in vitro experiments indicate that inhibiting MUC1 expression decreases cell proliferation, cell migration and invasion, cell survival and increases cell apoptosis. Moreover, lack of MUC1 in these cells profoundly altered their sensitivity to gemcitabine and 5-Fluorouracil chemotherapeutic drugs. In vivo MUC1-KD cell xenografts in SCID mice grew slower. Altogether, we show that MUC1 oncogenic mucin alters proliferation, migration, and invasion properties of pancreatic cancer cells and that these effects are mediated by p42–44 MAPK, Akt, Bcl-2 and MMP13 pathways.

  3. Biological Therapies for Cancer

    Science.gov (United States)

    ... Finally, lower white blood cell counts leave chemotherapy patients vulnerable to infections . Several growth factors that promote the growth of ... Flu-like symptoms Severe allergic reaction Urinary side effects Pain or burning sensation during urination Increased urgency or frequency of ...

  4. The Expression and Biological Significance of PD-L1 on Lung Cancer Cell Lines

    OpenAIRE

    Chen, Cheng; Chuanyong MU; Qiuxia QU; Zhu, Yibei; Sun, Jing; Zhang, Xueguang; Jian’an HUANG

    2009-01-01

    Background and objective Tumor-associated PD-L1 expression was recently shown to promote T-cell apoptosis and proposed as a potential mechanism of immune evasion by tumors. On the basis of the ability of tumor-associated PD-L1 to mediate activated T-cell death, it is likely that manipulation of the PD-L1 pathway at defined time points during the development of the T-cell antitumor immune response can enhance the efficacy of T-cell-based immunotherapy. Here, the levels of expression of PD-L1 o...

  5. The evolving biology and treatment of prostate cancer

    OpenAIRE

    Taichman, Russel S.; Loberg, Robert D; Mehra, Rohit; Kenneth J Pienta

    2007-01-01

    Since the effectiveness of androgen deprivation for treatment of advanced prostate cancer was first demonstrated, prevention strategies and medical therapies for prostate cancer have been based on understanding the biologic underpinnings of the disease. Prostate cancer treatment is one of the best examples of a systematic therapeutic approach to target not only the cancer cells themselves, but the microenvironment in which they are proliferating. As the population ages and prostate cancer pre...

  6. Research on the Relationship between Non-small Cell Lung Cancer with Neuroendocrine Differentiation and the Biological Characteristics and Prognosis

    Directory of Open Access Journals (Sweden)

    Jun ZHANG

    2010-09-01

    Full Text Available Background and objective Recently it has been proven that non-small cell lung cancer (NSCLC also had the feature of neuroendocrine (NE differentiation. The aim of this study is to investigate the correlation between NE differentiation of NSCLC and its biological behaviors, together with prognosis. Methods All NSCLC paraffin-embedded specimens and cases, followed up over than 3 years, were randomly obtained from 206 patients from January 2005 to December 2007, who underwent surgical resection and confirmed pathologically. All of them were not underwent radiation and chemotherapy before operation. Immunohistochemical Envision two-step method was used to detect the expressions of NSE, CgA and Syn. And all data were analyzed using SPSS statistics software and Kaplan-Meier survival curves were constructed, and Logrank test was also conducted. Results Of the 206 patients, 84 cases with NE differentiation (39.8% and CgA, NSE and Syn positive rates were 53 (25.7%, 104 (50.5%, 91 (44.2% respectively; a statistically significant difference between NSCLC with NE differentitation were showed. The positive expression of Syn was closely correlated with histological differentiation, lymph node metastasis. The survival of single-factor analysis by the Log-rank test showed that Syn had relation to the postoperative survival rate of patients (χ2=4.164, P=0.041, while the relevance between patients with NE and survival had no significant difference (P>0.05. Conclusion NE differentiation is an important indicator of biological behavior of NSCLC; and the detection of Syn markers of neuroendocrine differentiation may be recommended to detect NE differentiation of NSCLC, and the positive expression of Syn suggests poor prognosis.

  7. Squamous cell skin cancer

    Science.gov (United States)

    ... earliest form of squamous cell cancer is called Bowen disease (or squamous cell carcinoma in situ). This type ... cancer; Squamous cell carcinoma of the skin Images Bowen's disease on the hand Keratoacanthoma Keratoacanthoma Skin cancer, squamous ...

  8. Systems biology modeling reveals a possible mechanism of the tumor cell death upon oncogene inactivation in EGFR addicted cancers.

    Directory of Open Access Journals (Sweden)

    Jian-Ping Zhou

    Full Text Available Despite many evidences supporting the concept of "oncogene addiction" and many hypotheses rationalizing it, there is still a lack of detailed understanding to the precise molecular mechanism underlying oncogene addiction. In this account, we developed a mathematic model of epidermal growth factor receptor (EGFR associated signaling network, which involves EGFR-driving proliferation/pro-survival signaling pathways Ras/extracellular-signal-regulated kinase (ERK and phosphoinositol-3 kinase (PI3K/AKT, and pro-apoptotic signaling pathway apoptosis signal-regulating kinase 1 (ASK1/p38. In the setting of sustained EGFR activation, the simulation results show a persistent high level of proliferation/pro-survival effectors phospho-ERK and phospho-AKT, and a basal level of pro-apoptotic effector phospho-p38. The potential of p38 activation (apoptotic potential due to the elevated level of reactive oxygen species (ROS is largely suppressed by the negative crosstalk between PI3K/AKT and ASK1/p38 pathways. Upon acute EGFR inactivation, the survival signals decay rapidly, followed by a fast increase of the apoptotic signal due to the release of apoptotic potential. Overall, our systems biology modeling together with experimental validations reveals that inhibition of survival signals and concomitant release of apoptotic potential jointly contribute to the tumor cell death following the inhibition of addicted oncogene in EGFR addicted cancers.

  9. Comprehensive data-driven analysis of the impact of chemoinformatic structure on the genome-wide biological response profiles of cancer cells to 1159 drugs

    Directory of Open Access Journals (Sweden)

    Khan Suleiman A

    2012-05-01

    Full Text Available Abstract Background Detailed and systematic understanding of the biological effects of millions of available compounds on living cells is a significant challenge. As most compounds impact multiple targets and pathways, traditional methods for analyzing structure-function relationships are not comprehensive enough. Therefore more advanced integrative models are needed for predicting biological effects elicited by specific chemical features. As a step towards creating such computational links we developed a data-driven chemical systems biology approach to comprehensively study the relationship of 76 structural 3D-descriptors (VolSurf, chemical space of 1159 drugs with the microarray gene expression responses (biological space they elicited in three cancer cell lines. The analysis covering 11350 genes was based on data from the Connectivity Map. We decomposed the biological response profiles into components, each linked to a characteristic chemical descriptor profile. Results Integrated analysis of both the chemical and biological space was more informative than either dataset alone in predicting drug similarity as measured by shared protein targets. We identified ten major components that link distinct VolSurf chemical features across multiple compounds to specific cellular responses. For example, component 2 (hydrophobic properties strongly linked to DNA damage response, while component 3 (hydrogen bonding was associated with metabolic stress. Individual structural and biological features were often linked to one cell line only, such as leukemia cells (HL-60 specifically responding to cardiac glycosides. Conclusions In summary, our approach identified several novel links between specific chemical structure properties and distinct biological responses in cells incubated with these drugs. Importantly, the analysis focused on chemical-biological properties that emerge across multiple drugs. The decoding of such systematic relationships is necessary

  10. The biological difference between CD13+CD133+ and CD13¬CD133¬liver cancer cells and its clinical significance

    Directory of Open Access Journals (Sweden)

    Shi-long JIN

    2013-09-01

    Full Text Available Objective To compare the biological difference between CD13+CD133+ and CD13-CD133- hepatocellular carcinoma (HCC cells in HuH7 cell line and its clinical significance. Methods The status of proliferation, phase of the cell cycle, tumor formation in vivo, differentiation, and their chemoresistance to 5-FU and pirarubicin of CD13+CD133+ and CD13-CD133-HCC cells were studied to analyze the clinical implication of CD13+CD133+HCC cell subset. Results The proliferation rate of CD13+CD133+HCC cells was significantly higher than that of CD13-CD133-HCC cells. The cell-cycle phase study showed that 78.45% of the CD13+CD133+HCC cells were in the G0/G1 phase, 2.19% in G2/M phase, and 19.36% in S phase, while 62.18% CD13-CD133-HCC cells were in the G0/G1 phase, 11.88% in G2/M phase, and 25.95% in S phase. Limiting dilution analysis of HuH7 cells revealed that 1×103 CD13+CD133+ cells could form the tumor, while 1×105 CD13-CD133- cells did. CD13+CD133+ cells showed chemoresistance to 5-FU and pirarubicin, while other three subsets succumbed to the drugs. Conclusion CD13+CD133+ cancer cells in HuH7 showed the characteristics of cancer stem cells (CSCs, which might contribute to the relapse and metastasis of liver cancer, and they may be the main target for chemotherapy in human liver cancer.

  11. Biological Therapy in Treating Patients With Metastatic Cancer

    Science.gov (United States)

    2013-02-21

    Breast Cancer; Colorectal Cancer; Extrahepatic Bile Duct Cancer; Gallbladder Cancer; Gastric Cancer; Head and Neck Cancer; Liver Cancer; Lung Cancer; Metastatic Cancer; Ovarian Cancer; Pancreatic Cancer; Testicular Germ Cell Tumor

  12. Chemical and biological differentiation of three human breast cancer cell types using time-of-flight secondary ion mass spectrometry (TOF-SIMS)

    Energy Technology Data Exchange (ETDEWEB)

    Kulp, K S; Berman, E F; Knize, M G; Shattuck, D L; Nelson, E J; Wu, L; Montgomery, J L; Felton, J S; Wu, K J

    2006-01-09

    We use Time-of-Flight Secondary Ion Mass Spectrometry (TOF-SIMS) to image and classify individual cells based on their characteristic mass spectra. Using statistical data reduction on the large data sets generated during TOF-SIMS analysis, similar biological materials can be differentiated based on a combination of small changes in protein expression, metabolic activity and cell structure. We apply this powerful technique to image and differentiate three carcinoma-derived human breast cancer cell lines (MCF-7, T47D and MDA-MB-231). In homogenized cells, we show the ability to differentiate the cell types as well as cellular compartments (cytosol, nuclear and membrane). These studies illustrate the capacity of TOF-SIMS to characterize individual cells by chemical composition, which could ultimately be applied to detect and identify single aberrant cells within a normal cell population. Ultimately, we anticipate characterizing rare chemical changes that may provide clues to single cell progression within carcinogenic and metastatic pathways.

  13. Isolation, culture and biological characteristics of cancer stem cells%肿瘤干细胞的分离培养及生物学特性

    Institute of Scientific and Technical Information of China (English)

    王瑞海

    2011-01-01

    背景:肿瘤干细胞是一类具有自我更新能力、不定分化潜能的种子细胞,可以形成不同分化程度的肿瘤细胞,是恶性肿瘤不断生长、复发转移、无法被传统的放化疗方法彻底杀死的根源.目的:总结肿瘤干细胞的分离培养及其生物学特性.方法:由作者采用电子检索的方式,在万方数据库中检索以"肿瘤干细胞,分离培养,生物学特性" 为中文关键词,计算机检索1990-01/2010-12 有关肿瘤干细胞的分离培养及生物学特性的文章,经检索共查到相关文献45 篇.经阅读标题、摘要、全文后,排除内容重复、普通综述、Meta 分析类文章后,筛选纳入22 篇文献进行评价.结果与结论:在肺癌、胰腺癌、结肠癌、肝细胞癌、神经系统肿瘤等多种脏器肿瘤中,CD133 被作为鉴定肿瘤干细胞的特异性标记物之一.巢蛋白、波形蛋白和CD117 在神经系统肿瘤干细胞中有表达.CD44 及内皮素转化酶在肺癌肿瘤干细胞中的表达具有意义.CD44 和CD24 可作为分选人胰腺癌细胞株PANC-1 中肿瘤干细胞的表面标志.而CD166 在大肠癌肿瘤干细胞中高表达.%BACKGROUND: Cancer stem cells are a kind of seed cells with self-renewal capacity and uncertain differe ntiation potential, and can differentiate into tumor cells to different extents, which are the root cause of continued growth, metastasis and recurrence of malignant tumors which cannot be completely killed by traditional chemotherapy.OBJECTIVE: To review the isolation, culture and biological characteristics of cancer stem cells.METHODS: A computer retrieve of Wanfang database (1990-01/2010-12) was conducted for articles regarding the isolation,culture and biological characteristics of cancer stem cells using the keywords of “cancer stem cells, isolation and culture, biological characteristics” in Chinese. Repetitive articles, reviews and Meta analyses were excluded, and finally 22 of 45 articles were

  14. Fluid biopsy for circulating tumor cell identification in patients with early-and late-stage non-small cell lung cancer: a glimpse into lung cancer biology

    Science.gov (United States)

    Wendel, Marco; Bazhenova, Lyudmila; Boshuizen, Rogier; Kolatkar, Anand; Honnatti, Meghana; Cho, Edward H.; Marrinucci, Dena; Sandhu, Ajay; Perricone, Anthony; Thistlethwaite, Patricia; Bethel, Kelly; Nieva, Jorge; van den Heuvel, Michel; Kuhn, Peter

    2012-02-01

    Circulating tumor cell (CTC) counts are an established prognostic marker in metastatic prostate, breast and colorectal cancer, and recent data suggest a similar role in late stage non-small cell lung cancer (NSCLC). However, due to sensitivity constraints in current enrichment-based CTC detection technologies, there are few published data about CTC prevalence rates and morphologic heterogeneity in early-stage NSCLC, or the correlation of CTCs with disease progression and their usability for clinical staging. We investigated CTC counts, morphology and aggregation in early stage, locally advanced and metastatic NSCLC patients by using a fluid-phase biopsy approach that identifies CTCs without relying on surface-receptor-based enrichment and presents them in sufficiently high definition (HD) to satisfy diagnostic pathology image quality requirements. HD-CTCs were analyzed in blood samples from 78 chemotherapy-naïve NSCLC patients. 73% of the total population had a positive HD-CTC count (>0 CTC in 1 mL of blood) with a median of 4.4 HD-CTCs mL-1 (range 0-515.6) and a mean of 44.7 (±95.2) HD-CTCs mL-1. No significant difference in the medians of HD-CTC counts was detected between stage IV (n = 31, range 0-178.2), stage III (n = 34, range 0-515.6) and stages I/II (n = 13, range 0-442.3). Furthermore, HD-CTCs exhibited a uniformity in terms of molecular and physical characteristics such as fluorescent cytokeratin intensity, nuclear size, frequency of apoptosis and aggregate formation across the spectrum of staging. Our results demonstrate that despite stringent morphologic inclusion criteria for the definition of HD-CTCs, the HD-CTC assay shows high sensitivity in the detection and characterization of both early- and late-stage lung cancer CTCs. Extensive studies are warranted to investigate the prognostic value of CTC profiling in early-stage lung cancer. This finding has implications for the design of extensive studies examining screening, therapy and surveillance in

  15. Fluid biopsy for circulating tumor cell identification in patients with early-and late-stage non-small cell lung cancer: a glimpse into lung cancer biology

    International Nuclear Information System (INIS)

    Circulating tumor cell (CTC) counts are an established prognostic marker in metastatic prostate, breast and colorectal cancer, and recent data suggest a similar role in late stage non-small cell lung cancer (NSCLC). However, due to sensitivity constraints in current enrichment-based CTC detection technologies, there are few published data about CTC prevalence rates and morphologic heterogeneity in early-stage NSCLC, or the correlation of CTCs with disease progression and their usability for clinical staging. We investigated CTC counts, morphology and aggregation in early stage, locally advanced and metastatic NSCLC patients by using a fluid-phase biopsy approach that identifies CTCs without relying on surface-receptor-based enrichment and presents them in sufficiently high definition (HD) to satisfy diagnostic pathology image quality requirements. HD-CTCs were analyzed in blood samples from 78 chemotherapy-naïve NSCLC patients. 73% of the total population had a positive HD-CTC count (>0 CTC in 1 mL of blood) with a median of 4.4 HD-CTCs mL−1 (range 0–515.6) and a mean of 44.7 (±95.2) HD-CTCs mL−1. No significant difference in the medians of HD-CTC counts was detected between stage IV (n = 31, range 0–178.2), stage III (n = 34, range 0–515.6) and stages I/II (n = 13, range 0–442.3). Furthermore, HD-CTCs exhibited a uniformity in terms of molecular and physical characteristics such as fluorescent cytokeratin intensity, nuclear size, frequency of apoptosis and aggregate formation across the spectrum of staging. Our results demonstrate that despite stringent morphologic inclusion criteria for the definition of HD-CTCs, the HD-CTC assay shows high sensitivity in the detection and characterization of both early- and late-stage lung cancer CTCs. Extensive studies are warranted to investigate the prognostic value of CTC profiling in early-stage lung cancer. This finding has implications for the design of extensive studies examining screening, therapy and

  16. Interaction of ribosomal protein L22 with casein kinase 2α: a novel mechanism for understanding the biology of non-small cell lung cancer.

    Science.gov (United States)

    Yang, Mingxia; Sun, Haibo; He, Ji; Wang, Hong; Yu, Xiaowei; Ma, Lei; Zhu, Changliang

    2014-07-01

    Dysfunction of ribosomal proteins (RPs) may play an important role in molecular tumorigenesis, such as lung cancer, acting in extraribosomal functions. Many protein-protein interaction studies and genetic screens have confirmed the extraribosomal capacity of RPs. As reported, ribosomal protein L22 (RPL22) dysfunction could increase cancer risk. In the present study, we examined RPL22-protein complexes in lung cancer cells. Tandem affinity purification (TAP) was used to screen the RPL22-protein complexes, and GST pull-down experiments and confocal microscopy were used to assess the protein-protein interaction. The experiment of kinase assay was used to study the function of the RPL22-protein complexes. The results showed that several differentially expressed proteins were isolated and identified by LC-MS/MS, which revealed that one of the protein complexes included casein kinase 2α (CK2α). RPL22 and CK2α interact in vitro. RPL22 also inhibited CK2α substrate phosphorylation in vitro. This is the first report of the RPL22-CK2α relationship in lung cancer. Dysregulated CK2 may impact cell proliferation and apoptosis, key features of cancer cell biology. Our results indicate that RPL22 may be a candidate anticancer agent due to its CK2α-binding and -inhibitory functions in human lung cancer. PMID:24840952

  17. Comparative Phytochemical Analysis of Essential Oils from Different Biological Parts of Artemisia herba alba and Their Cytotoxic Effect on Cancer Cells.

    Directory of Open Access Journals (Sweden)

    Mounir Tilaoui

    Full Text Available Carrying out the chemical composition and antiproliferative effects against cancer cells from different biological parts of Artemisia herba alba.Essential oils were studied by gas chromatography coupled to mass spectrometry (GC-MS and their antitumoral activity was tested against P815 mastocytoma and BSR kidney carcinoma cell lines; also, in order to evaluate the effect on normal human cells, oils were tested against peripheral blood mononuclear cells PBMCs.Essential oils from leaves and aerial parts (mixture of capitulum and leaves were mainly composed by oxygenated sesquiterpenes 39.89% and 46.15% respectively; capitulum oil contained essentially monoterpenes (22.86% and monocyclic monoterpenes (21.48%; esters constituted the major fraction (62.8% of stem oil. Essential oils of different biological parts studied demonstrated a differential antiproliferative activity against P815 and BSR cancer cells; P815 cells are the most sensitive to the cytotoxic effect. Leaves and capitulum essential oils are more active than aerial parts. Interestingly, no cytotoxic effect of these essential oils was observed on peripheral blood mononuclear cells.Our results showed that the chemical composition variability of essential oils depends on the nature of botanical parts of Artemisia herba alba. Furthermore, we have demonstrated that the differential cytotoxic effect depends not only on the essential oils concentration, but also on the target cells and the botanical parts of essential oils used.

  18. Mechanistic Effects of Calcitriol in Cancer Biology

    Directory of Open Access Journals (Sweden)

    Lorenza Díaz

    2015-06-01

    Full Text Available Besides its classical biological effects on calcium and phosphorus homeostasis, calcitriol, the active vitamin D metabolite, has a broad variety of actions including anticancer effects that are mediated either transcriptionally and/or via non-genomic pathways. In the context of cancer, calcitriol regulates the cell cycle, induces apoptosis, promotes cell differentiation and acts as anti-inflammatory factor within the tumor microenvironment. In this review, we address the different mechanisms of action involved in the antineoplastic effects of calcitriol.

  19. An amperometric nanobiosensor using a biocompatible conjugate for early detection of metastatic cancer cells in biological fluid.

    Science.gov (United States)

    Pallela, Ramjee; Chandra, Pranjal; Noh, Hui-Bog; Shim, Yoon-Bo

    2016-11-15

    Metastasis is the major cause of cancer-associated death in humans, and its early diagnosis will help clinicians to develop suitable therapeutic strategies which may save life of cancer patients. In this direction, we designed an amperometric biosensor using a biocompatible conjugate to diagnose cancer metastasis by detecting epithelial cell adhesion molecule expressing metastatic cancer cells (Ep-MCCs). The sensor probe is fabricated by immobilizing monoclonal capture antibody (CapAnti) on the gold nanoparticles (AuNPs)/conducting polymer composite layer. The detection relies on a sandwich-type approach using a bioconjugate composed of reporter antibody (RepAnti), nanostructured collagen (nCOL), AuNPs, and hydrazine (Hyd) which served as a nonenzymatic electrocatalyst for the reduction of H2O2. The binding of Ep-MCCs with the sensor probe was confirmed using electrochemical impedance spectroscopy, cyclic voltammetry, and chronoamperometry. A dynamic range for the Ep-MCCs detection is determined between 45 and 100,000 Ep-MCCs/mL with the detection limit of 28±3 Ep-MCCs/mL. The proposed immunosensor is successfully applied to detect Ep-MCCs in serum and mixed cell samples and interferences due to nontarget cells and molecules present in the real sample matrix are also examined. The early stage of Ep-MCCs was examined by fluorescence-activated cell sorting assay, which confirms that the developed biosensor has detected Ep-MCCs in its early stage. PMID:27311113

  20. Deuterium effects in cancer biology

    International Nuclear Information System (INIS)

    Since its discovery many experiments were conducted for explaining the effects of deuterium on biological systems. It was observed, in many studies, that by increasing the deuterium concentration, structural, metabolic and functional alterations at different extents are produced, which can lead to organism's death. On the other hand effects of concentration reduction are much less studied. Existing data in literature, with regard to intrinsic deuterium reduction effects on different carcinomas are rather scarce. In vitro studies of deuterium level reduction has evidenced an inhibiting effect upon the cellular proliferation in different tumoral cellular lines: M14 cellular lines (human melanoma), PC3 (prostate cancer) and MCF7 (breast cancer). In vivo researches made on experimental tumours, have shown that the deuterium level reduction determines partial or complete regressions in xenotransplanted tumours, while in veterinary oncological clinic, partial or total tumoral regression were observed in different spontaneous tumours in dogs and cats. (authors)

  1. Mesangial cell biology

    Energy Technology Data Exchange (ETDEWEB)

    Abboud, Hanna E., E-mail: Abboud@uthscsa.edu

    2012-05-15

    Mesangial cells originate from the metanephric mesenchyme and maintain structural integrity of the glomerular microvascular bed and mesangial matrix homeostasis. In response to metabolic, immunologic or hemodynamic injury, these cells undergo apoptosis or acquire an activated phenotype and undergo hypertrophy, proliferation with excessive production of matrix proteins, growth factors, chemokines and cytokines. These soluble factors exert autocrine and paracrine effects on the cells or on other glomerular cells, respectively. MCs are primary targets of immune-mediated glomerular diseases such as IGA nephropathy or metabolic diseases such as diabetes. MCs may also respond to injury that primarily involves podocytes and endothelial cells or to structural and genetic abnormalities of the glomerular basement membrane. Signal transduction and oxidant stress pathways are activated in MCs and likely represent integrated input from multiple mediators. Such responses are convenient targets for therapeutic intervention. Studies in cultured MCs should be supplemented with in vivo studies as well as examination of freshly isolated cells from normal and diseases glomeruli. In addition to ex vivo morphologic studies in kidney cortex, cells should be studied in their natural environment, isolated glomeruli or even tissue slices. Identification of a specific marker of MCs should help genetic manipulation as well as selective therapeutic targeting of these cells. Identification of biological responses of MCs that are not mediated by the renin–angiotensin system should help development of novel and effective therapeutic strategies to treat diseases characterized by MC pathology.

  2. Micro and nanoplatforms for biological cell analysis

    DEFF Research Database (Denmark)

    Svendsen, Winnie Edith; Castillo, Jaime; Moresco, Jacob Lange;

    2010-01-01

    while working in a biological environment maintaining the cells viability and adding analyte are addressed and discussed. An example of a cell culturing chamber useful for both adherent and non-adherent cells, with the capability of adding analyte is given, a small discussion of in vitro cellular......In this paper some of the technological platforms developed in our group for biological cell analysis will be highlighted. The paper first presents a short introduction pinpointing the advantages of using micro and nano technology in cellular studies. The issues of requiring transient analysis...... sorting cells using dielectrophoresis will be given, aiming at early cancer detection....

  3. TRAF2 regulates the cytoplasmic/nuclear distribution of TRAF4 and its biological function in breast cancer cells

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, Xiaoli [Department of Pathology, The First Affiliated Hospital and College of Basic Medical Sciences of China Medical University, Shenyang 110001 (China); Wen, Zhifeng [Department of Neurosurgery, The First Affiliated Hospital, China Medical University, Shenyang 110001 (China); Sun, Limei; Wang, Jian; Song, Min; Wang, Enhua [Department of Pathology, The First Affiliated Hospital and College of Basic Medical Sciences of China Medical University, Shenyang 110001 (China); Mi, Xiaoyi, E-mail: xiaoyi_mi@163.com [Department of Pathology, The First Affiliated Hospital and College of Basic Medical Sciences of China Medical University, Shenyang 110001 (China)

    2013-06-28

    Highlights: •TRAF2 appears to interact with TRAF4 in breast cancer cell lines. •TRAF2 affects the localization and function of TRAF4 in breast cancer cell lines. •TRAF4 may play an important role in the activation of NF-κB via TRAF2. -- Abstract: Although numerous studies have shown that tumor necrosis factor receptor-associated factor 4 (TRAF4) plays an important role in the carcinogenesis of many tumor types, its exact molecular mechanism remains elusive. In this study, we examined the regulation function of TRAF2 to the cytoplasmic/nuclear distribution of TRAF4 in the breast cancer cell line. Using cell immunofluorescent staining, we found that TRAF2 and TRAF4 were co-localized to the cytoplasm in MCF-7 cells. Co-immunoprecipitation showed that TRAF2 could interact with TRAF4 in MCF-10A, MCF-7 and MDA-MB-231 cell lines. Western blotting showed TRAF2 depletion by targeted siRNA in MDA-MB-231 cells led to reduced TRAF4 expression in the cytoplasm and augmented TRAF4 expression in the nucleus. Cytoplasmic expression of TRAF4 was augmented and nuclear expression was reduced when MCF-7 cells were transfected with hTRAF2pLPCX-HA-Flag/P874. MCF-7 cells expressing hTRAF2pLPCX-HA-Flag/P874 had enhanced cell proliferation rates. The nuclear expression of NF-κB significantly increased after TNF-α treatment. When hTRAF2pLPCX-HA-Flag/P874 and the siRNA-TRAF4 plasmid were cotransfected, the nuclear expression of NF-κB was significantly reduced compared with cells transfected with hTRAF2pLPCX-HA-Flag/P874 only. In conclusion, TRAF2 appears to interact with TRAF4 and affect the localization of TRAF4 in breast cancer cell lines. The overexpression of TRAF2 augmented the cytoplasmic expression of TRAF4 which promoted cell proliferation and inhibited cell apoptosis by activating NF-κB nuclear transcription. TRAF4 may play an important role in the activation of NF-κB via TRAF2.

  4. Selenium Metabolism in Cancer Cells: The Combined Application of XAS and XFM Techniques to the Problem of Selenium Speciation in Biological Systems

    Directory of Open Access Journals (Sweden)

    Hugh H. Harris

    2013-05-01

    Full Text Available Determining the speciation of selenium in vivo is crucial to understanding the biological activity of this essential element, which is a popular dietary supplement due to its anti-cancer properties. Hyphenated techniques that combine separation and detection methods are traditionally and effectively used in selenium speciation analysis, but require extensive sample preparation that may affect speciation. Synchrotron-based X-ray absorption and fluorescence techniques offer an alternative approach to selenium speciation analysis that requires minimal sample preparation. We present a brief summary of some key HPLC-ICP-MS and ESI-MS/MS studies of the speciation of selenium in cells and rat tissues. We review the results of a top-down approach to selenium speciation in human lung cancer cells that aims to link the speciation and distribution of selenium to its biological activity using a combination of X-ray absorption spectroscopy (XAS and X-ray fluorescence microscopy (XFM. The results of this approach highlight the distinct fates of selenomethionine, methylselenocysteine and selenite in terms of their speciation and distribution within cells: organic selenium metabolites were widely distributed throughout the cells, whereas inorganic selenium metabolites were compartmentalized and associated with copper. New data from the XFM mapping of electrophoretically-separated cell lysates show the distribution of selenium in the proteins of selenomethionine-treated cells. Future applications of this top-down approach are discussed.

  5. Biological effects of progestins in breast cancer.

    Science.gov (United States)

    Pasqualini, J R; Ebert, C; Chetrite, G S

    2001-12-01

    The action of progestins is derived from many factors: structure, affinity for the progesterone receptor or for other steroid receptors, the target tissue considered, the biological response, the experimental conditions, the dose and metabolic transformation. The proliferative response to progestins in human breast cancer cells is contradictory: some progestins inhibit, others stimulate, have no effect at all, or have a dual action. For instance, medroxyprogesterone acetate has a stimulatory effect on breast cancer cells after a short period of treatment, but this effect becomes inhibitory when treatment is prolonged. It has been demonstrated that, in hormone-dependent breast cancer cells, various progestins (nomegestrol acetate, medrogestone, promegestone) are potent sulfatase inhibitory agents. The progestins can also involve the inhibition of the mRNA expression of this enzyme. In another series of studies it was also demonstrated that some progestins are very active in inhibiting 17beta-hydroxysteroid dehydrogenase for the conversion of estrone to estradiol. More recently it was observed that the progestins promegestone and medrogestone stimulate sulfotransferase for the formation of estrogen sulfates. Consequently, the action of progestins in blocking estradiol formation via sulfatase, or in stimulating the effect on sulfotransferase activity, can open interesting and new possibilities in clinical applications in breast cancer. PMID:12227886

  6. Effect of proton and gamma irradiation on human lung carcinoma cells: Gene expression, cell cycle, cell death, epithelial-mesenchymal transition and cancer-stem cell trait as biological end points.

    Science.gov (United States)

    Narang, Himanshi; Kumar, Amit; Bhat, Nagesh; Pandey, Badri N; Ghosh, Anu

    2015-10-01

    Proton beam therapy is a cutting edge modality over conventional gamma radiotherapy because of its physical dose deposition advantage. However, not much is known about its biological effects vis-a-vis gamma irradiation. Here we investigated the effect of proton- and gamma- irradiation on cell cycle, death, epithelial-mesenchymal transition (EMT) and "stemness" in human non-small cell lung carcinoma cells (A549). Proton beam (3MeV) was two times more cytotoxic than gamma radiation and induced higher and longer cell cycle arrest. At equivalent doses, numbers of genes responsive to proton irradiation were ten times higher than those responsive to gamma irradiation. At equitoxic doses, the proton-irradiated cells had reduced cell adhesion and migration ability as compared to the gamma-irradiated cells. It was also more effective in reducing population of Cancer Stem Cell (CSC) like cells as revealed by aldehyde dehydrogenase activity and surface phenotyping by CD44(+), a CSC marker. These results can have significant implications for proton therapy in the context of suppression of molecular and cellular processes that are fundamental to tumor expansion. PMID:26278043

  7. Illuminating Cell Biology

    Science.gov (United States)

    2002-01-01

    NASA's Ames Research Center awarded Ciencia, Inc., a Small Business Innovation Research contract to develop the Cell Fluorescence Analysis System (CFAS) to address the size, mass, and power constraints of using fluorescence spectroscopy in the International Space Station's Life Science Research Facility. The system will play an important role in studying biological specimen's long-term adaptation to microgravity. Commercial applications for the technology include diverse markets such as food safety, in situ environmental monitoring, online process analysis, genomics and DNA chips, and non-invasive diagnostics. Ciencia has already sold the system to the private sector for biosensor applications.

  8. Progesterone receptors - animal models and cell signalling in breast cancer: Diverse activation pathways for the progesterone receptor: possible implications for breast biology and cancer

    International Nuclear Information System (INIS)

    Progesterone and estradiol, and their nuclear receptors, play essential roles in the physiology of the reproductive tract, the mammary gland and the nervous system. Estrogens have traditionally been considered associated with an increased risk of breast cancer. There is, however, compelling evidence that progesterone plays an important role in breast cell proliferation and cancer. Herein, we review the possible role of progestins and the progesterone receptor-associated signaling pathways in the development of breast cancer, as well as the therapeutic possibilities arising from our growing knowledge of the activation of the progesterone receptor by other proliferative mechanisms

  9. Automatic detection of biological cells

    International Nuclear Information System (INIS)

    The present research work has dealt with the analysis of biological cell images in general, and more specially with the cervical cells. This work was carried out in order to develop an automaton leading to a better prevention of cancer through automated mass screening. The device has been implemented on Motorola 68.000 microprocessor system. The automaton carries out cell nucleus analysis in several steps. The main steps are: - First: the automaton focuses on an individual cell nucleus among the smear's cell (about 10.000), - Second: it process each nucleus image. The digital processing yields geometrical of the nucleus (area and perimeter) for each cell. These data are stored in a local memory for further discriminant analysis by a microcomputer. In this way smears are classed in two groups: hale smears and uncertain smears. The automaton uses a wired logic for image acquisition and its software algorithms provide image reconstruction. The reconstruction algorithms are general purpose. Tests have proved that they can reconstruct any two dimensional images independently of its geometrical form. Moreover they can make the reconstruction of any image among the several images present in observation field. The processing times registered during the tests (for different cases) were situated, all of them, below three minutes for 10,000 images (each of them formed by an average of 450 pixels). The interest of the method is generality and speed. The only restriction is the primary device sensor (CCD linear array) length. Thus the automaton application can be extended beyond the biological image field. (author)

  10. Mammalian cell biology

    International Nuclear Information System (INIS)

    Progress is reported on studies of the molecular biology and functional changes in cultured mammalian cells following exposure to x radiation, uv radiation, fission neutrons, or various chemical environmental pollutants alone or in combinations. Emphasis was placed on the separate and combined effects of polycyclic aromatic hydrocarbons released during combustion of fossil fuels and ionizing and nonionizing radiations. Sun lamps, which emit a continuous spectrum of near ultraviolet light of 290 nm to 315 nm were used for studies of predictive cell killing due to sunlight. Results showed that exposure to uv light (254 nm) may not be adequate to predict effects produced by sunlight. Data are included from studies on single-strand breaks and repair in DNA of cultured hamster cells exposed to uv or nearultraviolet light. The possible interactions of the polycyclic aromatic hydrocarbon 7,12-dimethylbenz(a)-anthracene (DmBA) alone or combined with exposure to x radiation, uv radiation (254 nm) or near ultraviolet simulating sunlight were compared for effects on cell survival

  11. Networks in Cell Biology = Modelling cell biology with networks

    OpenAIRE

    Buchanan, Mark; Caldarelli, Guido; De Los Rios, Paolo; Rao, Francesco; Vendruscolo, M.

    2010-01-01

    The science of complex biological networks is transforming research in areas ranging from evolutionary biology to medicine. This is the first book on the subject, providing a comprehensive introduction to complex network science and its biological applications. With contributions from key leaders in both network theory and modern cell biology, this book discusses the network science that is increasingly foundational for systems biology and the quantitative understanding of living systems. It ...

  12. Metabolites of Ginger Component [6]-Shogaol Remain Bioactive in Cancer Cells and Have Low Toxicity in Normal Cells: Chemical Synthesis and Biological Evaluation

    OpenAIRE

    Yingdong Zhu; Warin, Renaud F.; Soroka, Dominique N.; Huadong Chen; Shengmin Sang

    2013-01-01

    Our previous study found that [6]-shogaol, a major bioactive component in ginger, is extensively metabolized in cancer cells and in mice. It is unclear whether these metabolites retain bioactivity. The aim of the current study is to synthesize the major metabolites of [6]-shogaol and evaluate their inhibition of growth and induction of apoptosis in human cancer cells. Twelve metabolites of [6]-shogaol (M1, M2, and M4-M13) were successfully synthesized using simple and easily accessible chemic...

  13. Advances in molecular biology of lung disease: aiming for precision therapy in non-small cell lung cancer.

    Science.gov (United States)

    Rooney, Claire; Sethi, Tariq

    2015-10-01

    Lung cancer is the principal cause of cancer-related mortality in the developed world, accounting for almost one-quarter of all cancer deaths. Traditional treatment algorithms have largely relied on histologic subtype and have comprised pragmatic chemotherapy regimens with limited efficacy. However, because our understanding of the molecular basis of disease in non-small cell lung cancer (NSCLC) has improved exponentially, it has become apparent that NSCLC can be radically subdivided, or molecularly characterized, based on recurrent driver mutations occurring in specific oncogenes. We know that the presence of such mutations leads to constitutive activation of aberrant signaling proteins that initiate, progress, and sustain tumorigenesis. This persistence of the malignant phenotype is referred to as "oncogene addiction." On this basis, a paradigm shift in treatment approach has occurred. Rational, targeted therapies have been developed, the first being tyrosine kinase inhibitors (TKIs), which entered the clinical arena > 10 years ago. These were tremendously successful, significantly affecting the natural history of NSCLC and improving patient outcomes. However, the benefits of these drugs are somewhat limited by the emergence of adaptive resistance mechanisms, and efforts to tackle this phenomenon are ongoing. A better understanding of all types of oncogene-driven NSCLC and the occurrence of TKI resistance will help us to further develop second- and third-generation small molecule inhibitors and will expand our range of precision therapies for this disease. PMID:26182407

  14. Biology of SNU Cell Lines

    OpenAIRE

    Ku, Ja-Lok; Park, Jae-Gahb

    2005-01-01

    SNU (Seoul National University) cell lines have been established from Korean cancer patients since 1982. Of these 109 cell lines have been characterized and reported, i.e., 17 colorectal carcinoma, 12 hepatocellular carcinoma, 11 gastric carcinoma, 12 uterine cervical carcinoma, 17 B-lymphoblastoid cell lines derived from cancer patients, 5 ovarian carcinoma, 3 malignant mixed Mllerian tumor, 6 laryngeal squamous cell carcinoma, 7 renal cell carcinoma, 9 brain tumor, 6 biliary tract, and 4 pa...

  15. Molecular biology of pancreatic cancer

    Institute of Scientific and Technical Information of China (English)

    Miroslav Zavoral; Petra Minarikova; Filip Zavada; Cyril Salek; Marek Minarik

    2011-01-01

    In spite of continuous research efforts directed at early detection and treatment of pancreatic cancer, the outlook for patients affected by the disease remains dismal. With most cases still being diagnosed at advanced stages, no improvement in survival prognosis is achieved with current diagnostic imaging approaches. In the absence of a dominant precancerous condition, several risk factors have been identified including family history, chronic pancreatitis, smoking, diabetes mellitus, as well as certain genetic disorders such as hereditary pancreatitis, cystic fibrosis, familial atypical multiple Most pancreatic carcinomas, however, remain sporadic. Current progress in experimental molecular techniques has enabled detailed understanding of the molecular processes of pancreatic cancer development. According to the latest information, malignant pancreatic transformation involves multiple oncogenes and tumor-suppressor genes that are involved in a variety of signaling pathways. The most characteristic aberrations (somatic point mutations and allelic losses) affect oncogenes and tumor-suppressor genes within RAS, AKT and Wnt signaling, and have a key role in transcription and proliferation, as well as systems that regulate the cell cycle (SMAD/DPC, CDKN2A/p16) and apoptosis (TP53). Understanding of the underlying molecular mechanisms should promote development of new methodology for early diagnosis and facilitate improvement in current approaches for pancreatic cancer treatment.

  16. Ki-67 Proliferation Index in Gastric Cancer - Biologic Significance

    OpenAIRE

    Nabais, C.; Caldeira Fradique, A; Oliveira, M.; Quaresma, L.; Gualdino Silva, J; Vasconcelos, V.; Sacadura, J.; Costa, L; Cabrita, F; Mateus Marques, R; Esteves, J.; Fernandez, G.; Guedes da Silva

    2016-01-01

    Objectives/Introdution: Ki-67 protein has been used as an indicator of proliferation activity in tumor cells. In gastric cancer the prognostic value has not been fully understood. This study was designed to assess the biologic significance of Ki-67 proliferation index (PI) in gastric cancer. Material/Methods: Seventy-two patients with gastric cancer were evaluated. These patients underwent gastric resection, and the tumor tissue was stained immunohistochemically. Ki-67 PI was defi...

  17. Biological Networks for Cancer Candidate Biomarkers Discovery

    Science.gov (United States)

    Yan, Wenying; Xue, Wenjin; Chen, Jiajia; Hu, Guang

    2016-01-01

    Due to its extraordinary heterogeneity and complexity, cancer is often proposed as a model case of a systems biology disease or network disease. There is a critical need of effective biomarkers for cancer diagnosis and/or outcome prediction from system level analyses. Methods based on integrating omics data into networks have the potential to revolutionize the identification of cancer biomarkers. Deciphering the biological networks underlying cancer is undoubtedly important for understanding the molecular mechanisms of the disease and identifying effective biomarkers. In this review, the networks constructed for cancer biomarker discovery based on different omics level data are described and illustrated from recent advances in the field.

  18. Biological Networks for Cancer Candidate Biomarkers Discovery.

    Science.gov (United States)

    Yan, Wenying; Xue, Wenjin; Chen, Jiajia; Hu, Guang

    2016-01-01

    Due to its extraordinary heterogeneity and complexity, cancer is often proposed as a model case of a systems biology disease or network disease. There is a critical need of effective biomarkers for cancer diagnosis and/or outcome prediction from system level analyses. Methods based on integrating omics data into networks have the potential to revolutionize the identification of cancer biomarkers. Deciphering the biological networks underlying cancer is undoubtedly important for understanding the molecular mechanisms of the disease and identifying effective biomarkers. In this review, the networks constructed for cancer biomarker discovery based on different omics level data are described and illustrated from recent advances in the field. PMID:27625573

  19. Lung Cancer Stem Cells

    Directory of Open Access Journals (Sweden)

    Sharon R. Pine

    2008-01-01

    Full Text Available Lung cancer remains a major cause of cancer-related lethality because of high incidence and recurrence in spite of significant advances in staging and therapies. Recent data indicates that stem cells situated throughout the airways may initiate cancer formation. These putative stem cells maintain protumorigenic characteristics including high proliferative capacity, multipotent differentiation, drug resistance and long lifespan relative to other cells. Stem cell signaling and differentiation pathways are maintained within distinct cancer types, and destabilization of this machinery may participate in maintenance of cancer stem cells. Characterization of lung cancer stem cells is an area of active research and is critical for developing novel therapies. This review summarizes the current knowledge on stem cell signaling pathways and cell markers used to identify the lung cancer stem cells.

  20. Cell phones and cancer

    Science.gov (United States)

    Cancer and cell phones; Do cell phones cause cancer? ... Several major studies show no link between cell phones and cancer at this time. However, since the information available is based on short-term studies, the impact of many years of ...

  1. Gossypol Induced Cell Death in DU 145 Prostate Cancer Cells

    OpenAIRE

    Kennelly, Susan

    2010-01-01

    Cancer Biology Tumourigenesis is a multistep process which includes the transformation of healthy cells into extremely malignant cells, caused by the disruption of normal tissue homeostasis. Hanahan and Weinberg propose that there are a common set of 'acquired capabilities' that most if not all cancers posses's in order to survive and proliferate despite changes in their normal cell physiology during cancer development (Hanahan and Weinberg, 2000). These "Hallmarks of Cancer", according to...

  2. Understanding Cancer Prognosis

    Medline Plus

    Full Text Available ... Renal Cell) Cancer Leukemia Lung Cancer Lymphoma Pancreatic Cancer Prostate Cancer Skin Cancer Thyroid Cancer Uterine Cancer All ... Cancer Biology Cancer Genomics Causes of Cancer Diagnosis Prevention Screening & Early Detection Treatment Cancer & Public Health Cancer ...

  3. Metastasis-Initiating Cells in Renal Cancer

    OpenAIRE

    Khan, Mohammed I.; Czarnecka, Anna M; Duchnowska, Renata; Kukwa, Wojciech; Szczylik, Cezary

    2013-01-01

    Metastasis is a complex process that propagates cells from the primary or initial site of the cancer occurrence to distant parts of the body. Cancer cells break from the cancer site and circulate through the bloodstream or lymph vessels, allowing them to reach nearly all parts of the body. These circulating tumour cells (CTCs) contain specialized metastasis-initiating cells (MICs) that reside in the biological heterogeneous primary tumour. Researchers have hypothesized that metastasis of rena...

  4. Cancer Stem Cells

    OpenAIRE

    Katarzyna Wieczorek; Jolanta Niewiarowska

    2008-01-01

    Cancer stem cell theory gains increasingly greater significance in the world of medicine. Numerous findings of scientific research in vivo and in vitro indicate that it is the population of undifferentiated, self-renewing cells which is responsible for recurrence of cancer and metastasis. Similarly to normal stem cells, cancer stem cells (CSC) function in the environment of the other cells of the organism, called the niche, where they receive signals for differentiation and proliferation proc...

  5. Biological Effect of a Hybrid Anticancer Agent Based on Kinase and Histone Deacetylase Inhibitors on Triple-Negative (MDA-MB231) Breast Cancer Cells.

    Science.gov (United States)

    Librizzi, Mariangela; Spencer, John; Luparello, Claudio

    2016-01-01

    We examined the effects of the histone deacetylase inhibitor (HDACi) suberoylanilide hydroxamic acid (SAHA) combined with the vascular endothelial growth factor receptor-1/2 inhibitor (3Z)-5-hydroxy-3-(1H-pyrrol-2-ylmethylidene)-2,3-dihydro-1H-indol-2-one on MDA-MB-231 breast cancer cells (triple-negative) in the form of both a cocktail of the separate compounds and a chemically synthesized hybrid (N-hydroxy-N'-[(3Z)-2-oxo-3-(1H-pyrrol-2-ylmethylidene)-2,3-dihydro-1H-indol-5-yl]octanediamide). Comparative flow cytometric and Western blot analyses were performed on cocktail- and hybrid-treated cells to evaluate cell cycle distribution, autophagy/apoptosis modulation, and mitochondrial metabolic state in order to understand the cellular basis of the cytotoxic effect. Cell cycle analysis showed a perturbation of the rate of progression through the cycle, with aspects of redistribution of cells over different cycle phases for the two treatments. In addition, the results suggest that the two distinct classes of compounds under investigation could induce cell death by different preferential pathways, i.e., autophagy inhibition (the cocktail) or apoptosis promotion (the hybrid), thus confirming the enhanced potential of the hybrid approach vs. the combination approach in finely tuning the biological activities of target cells and also showing the hybrid compound as an additional promising drug-like molecule for the prevention or therapy of "aggressive" breast carcinoma. PMID:27483253

  6. Testicular cancer: biology and biomarkers.

    Science.gov (United States)

    Looijenga, Leendert H J; Stoop, Hans; Biermann, Katharina

    2014-03-01

    The term "human germ cell tumors" (GCTs) refers to a heterogeneous group of neoplasms, all with a defined histological appearance. They have specific epidemiological characteristics, clinical behavior, and pathogenesis. Histologically, GCTs contain various tissue elements, which are homologs of normal embryogenesis. We have proposed a subclassification of GCTs in five subtypes, three of which preferentially occur in the testis. These include teratomas and yolk sac tumors of neonates and infants (type I), seminomas and nonseminomas of (predominantly) adolescents and adults (type II), and spermatocytic seminomas of the elderly (type III). Both spontaneous and induced animal models have been reported, of which the relevance for human GCTs is still to be clarified. Multidisciplinary studies have recently shed new light on the (earliest steps in the) pathogenesis of GCTs, mainly in regard of malignant type II GCTs (germ cell cancer (GCC)). This review discusses novel understanding of the pathogenesis of (mainly) GCC, focusing on identification of informative diagnostic markers suitable for application in a clinical setting. These include OCT3/4, SOX9/FOXL2, SOX17/SOX2, as well as embryonic microRNAs. These markers have been identified through studies on normal embryogenesis, specifically related to the gonads, including the germ cell lineage. Their strengths and limitations are discussed as well as the expected future approach to identify the group of individuals at highest risk for development of a GCC. The latter would allow screening of defined populations, early diagnosis, optimal follow-up, and potentially early treatment, preventing long-term side effects of systemic treatment. PMID:24487784

  7. Lung Cancer Stem Cells

    OpenAIRE

    Pine, Sharon R.; Blair Marshall; Lyuba Varticovski

    2008-01-01

    Lung cancer remains a major cause of cancer-related lethality because of high incidence and recurrence in spite of significant advances in staging and therapies. Recent data indicates that stem cells situated throughout the airways may initiate cancer formation. These putative stem cells maintain protumorigenic characteristics including high proliferative capacity, multipotent differentiation, drug resistance and long lifespan relative to other cells. Stem cell signaling and differentiation p...

  8. Gastric cancer and trastuzumab: first biologic therapy in gastric cancer

    OpenAIRE

    Gunturu, Krishna S; Woo, Yanghee; Beaubier, Nike; Remotti, Helen E.; Saif, M. Wasif

    2013-01-01

    Gastric cancer remains difficult to cure and has a poor overall prognosis. Chemotherapy and multimodality therapy has shown some benefit in the treatment of gastric cancer. Current therapies for gastric cancer have their limitations; thus, we are in need of newer treatment options including targeted therapies. Here, we review the biologic therapy with trastuzumab in human epidermal growth factor receptor 2 (HER2)+ gastric cancer.

  9. Breast cancer stem cells

    OpenAIRE

    Owens, Thomas W.; Naylor, Matthew J.

    2013-01-01

    Cancer metastasis, resistance to therapies and disease recurrence are significant hurdles to successful treatment of breast cancer. Identifying mechanisms by which cancer spreads, survives treatment regimes and regenerates more aggressive tumors are critical to improving patient survival. Substantial evidence gathered over the last 10 years suggests that breast cancer progression and recurrence is supported by cancer stem cells (CSCs). Understanding how CSCs form and how they contribute to th...

  10. Cancer Stem Cells: From Bench to Bedside

    OpenAIRE

    Jones, Richard J.; Matsui, William

    2007-01-01

    Objective clinical responses to anticancer treatments often do not translate into substantial improvements in overall survival. Recent data suggesting many cancers arise from rare self-renewing cells (cancer stem cells) that are biologically distinct from their more numerous differentiated progeny, may explain this paradox. Current anticancer therapies have been developed to target the bulk of the tumor mass (i.e., the differentiated cancer cells). Although treatments directed against the bul...

  11. Dielectrophoretic separation of colorectal cancer cells

    OpenAIRE

    Yang, Fang; Yang, Xiaoming; Jiang, Hong; Bulkhaults, Phillip; Wood, Patricia; Hrushesky, William; Wang, Guiren

    2010-01-01

    Separation of colorectal cancer cells from other biological materials is important for stool-based diagnosis of colorectal cancer. In this paper, we use conventional dielectrophoresis in a microfluidic chip to manipulate and isolate HCT116 colorectal cancer cells. It is noticed that at a particular alternating current frequency band, the HCT116 cells are clearly deflected to a side channel from the main channel after the electric activation of an electrode pair. This motion caused by negative...

  12. Stages of Renal Cell Cancer

    Science.gov (United States)

    ... cell cancer is a disease in which malignant (cancer) cells form in tubules of the kidney. Renal cell ... diagnosed, tests are done to find out if cancer cells have spread within the kidney or to other ...

  13. Cancer Stem Cells in Lung Tumorigenesis

    OpenAIRE

    Kratz, Johannes R.; Yagui-Beltrán, Adam; Jablons, David M.

    2010-01-01

    Although stem cells were discovered more than 50 years ago, we have only recently begun to understand their potential importance in cancer biology. Recent advances in our ability to describe, isolate, and study lung stem cell populations has led to a growing recognition of the central importance cells with stem cell-like properties may have in lung tumorigenesis. This article reviews the major studies supporting the existence and importance of cancer stem cells in lung tumorigenesis. Continue...

  14. Skin Cancer: Biology, Risk Factors & Treatment | NIH MedlinePlus the Magazine

    Science.gov (United States)

    ... of this page please turn Javascript on. Feature: Skin Cancer Skin Cancer: Biology, Risk Factors & Treatment Past Issues / Summer ... that make up tissues. Tissues make up the skin and other organs of the body. Normal cells ...

  15. Road for understanding cancer stem cells

    DEFF Research Database (Denmark)

    Serakinci, Nedime; Erzik, Can

    2007-01-01

    offer an opportunity to use these cells as future therapeutic targets. Therefore, model systems in this field have become very important and useful. This review will focus on the state of knowledge on cancer stem cell research, including cell line models for cancer stem cells. The latter will, as models......There is increasing evidence suggesting that stem cells are susceptive to carcinogenesis and, consequently, can be the origin of many cancers. Recently, the neoplastic potential of stem cells has been supported by many groups showing the existence of subpopulations with stem cell characteristics...... in tumor biopsies such as brain and breast. Evidence supporting the cancer stem cell hypothesis has gained impact due to progress in stem cell biology and development of new models to validate the self-renewal potential of stem cells. Recent evidence on the possible identification of cancer stem cells may...

  16. Gastric Cancer Stem Cells

    OpenAIRE

    Takaishi, Shigeo; Okumura, Tomoyuki; Timothy C Wang

    2008-01-01

    Cancer stem cells are defined as the unique subpopulation in the tumors that possess the ability to initiate tumor growth and sustain self-renewal as well as metastatic potential. Accumulating evidence in recent years strongly indicate the existence of cancer stem cells in solid tumors of a wide variety of organs. In this review, we will discuss the possible existence of a gastric cancer stem cell. Our recent data suggest that a subpopulation with a defined marker shows spheroid colony format...

  17. Cancer stem cell metabolism

    OpenAIRE

    Peiris-Pagès, Maria; Martinez-Outschoorn, Ubaldo E.; Pestell, Richard G.; Sotgia, Federica; Lisanti, Michael P

    2016-01-01

    Cancer is now viewed as a stem cell disease. There is still no consensus on the metabolic characteristics of cancer stem cells, with several studies indicating that they are mainly glycolytic and others pointing instead to mitochondrial metabolism as their principal source of energy. Cancer stem cells also seem to adapt their metabolism to microenvironmental changes by conveniently shifting energy production from one pathway to another, or by acquiring intermediate metabolic phenotypes. Deter...

  18. Liver Cancer Stem Cells

    OpenAIRE

    Sameh Mikhail; Aiwu Ruth He

    2011-01-01

    Hepatocellular carcinoma is the most common primary malignancy of the liver in adults. It is also the fifth most common solid cancer worldwide and the third leading cause of cancer-related death. Recent research supports that liver cancer is a disease of adult stem cells. From the models of experimental hepatocarcinogenesis, there may be at least three distinct cell lineages with progenitor properties susceptible to neoplastic transformation. Identification of specific cell surface markers fo...

  19. Cancer Stem Cells in the Thyroid

    Science.gov (United States)

    Nagayama, Yuji; Shimamura, Mika; Mitsutake, Norisato

    2016-01-01

    The cancer stem cell (CSC) model posits that CSCs are a small, biologically distinct subpopulation of cancer cells in each tumor that have self-renewal and multi-lineage potential, and are critical for cancer initiation, metastasis, recurrence, and therapy-resistance. Numerous studies have linked CSCs to thyroid biology, but the candidate markers and signal transduction pathways that drive thyroid CSC growth are controversial, the origin(s) of thyroid CSCs remain elusive, and it is unclear whether thyroid CSC biology is consistent with the original hierarchical CSC model or the more recent dynamic CSC model. Here, we critically review the thyroid CSC literature with an emphasis on research that confirmed the presence of thyroid CSCs by in vitro sphere formation or in vivo tumor formation assays with dispersed cells from thyroid cancer tissues or bona fide thyroid cancer cell lines. Future perspectives of thyroid CSC research are also discussed. PMID:26973599

  20. Breast cancer biology for the radiation oncologist

    International Nuclear Information System (INIS)

    This is the first textbook of its kind devoted to describing the biological complexities of breast cancer in a way that is relevant to the radiation oncologist. Radiation Oncology has long treated breast cancer as a single biological entity, with all treatment decisions being based on clinical and pathologic risk factors. We are now beginning to understand that biological subtypes of breast cancer may have different risks of recurrence as well as different intrinsic sensitivity to radiotherapy. Multi-gene arrays that have for years been used to predict the risk of distant recurrence and the value of systemic chemotherapy may also have utility in predicting the risk of local recurrence. Additionally, the targeted agents used to treat breast cancer may interact with radiotherapy in ways that can be beneficial or undesirable. All of these emerging issues are extensively discussed in this book, and practical evidence-based treatment recommendations are presented whenever possible.

  1. Breast cancer biology for the radiation oncologist

    Energy Technology Data Exchange (ETDEWEB)

    Strauss, Jonathan [Northwestern Univ., Chicago, IL (United States). Dept. of Radiation Oncology; Small, William [Loyola Univ. Chicago, Maywood, IL (United States). Stritch School of Medicine, Cardianl Bernardin Cancer Center; Woloschak, Gayle E. (ed.) [Northwestern Univ. Feinberg, Chicago, IL (United States). School of Medicine

    2015-10-01

    This is the first textbook of its kind devoted to describing the biological complexities of breast cancer in a way that is relevant to the radiation oncologist. Radiation Oncology has long treated breast cancer as a single biological entity, with all treatment decisions being based on clinical and pathologic risk factors. We are now beginning to understand that biological subtypes of breast cancer may have different risks of recurrence as well as different intrinsic sensitivity to radiotherapy. Multi-gene arrays that have for years been used to predict the risk of distant recurrence and the value of systemic chemotherapy may also have utility in predicting the risk of local recurrence. Additionally, the targeted agents used to treat breast cancer may interact with radiotherapy in ways that can be beneficial or undesirable. All of these emerging issues are extensively discussed in this book, and practical evidence-based treatment recommendations are presented whenever possible.

  2. Mammalian cell biology

    International Nuclear Information System (INIS)

    Studies of the action of N-ethylmaleimide (NEM), as an inhibitor of repair of x radioinduced injuries were extended from synchronous Chinese hamster cells to synchronous human HeLa cells. These studies showed a similar mode of action in both cell types lending support to the notion that conclusions may be extracted from such observations that are of fairly general applicability to mammalian cells. Radiation studies with NEM are being extended to hypoxic cells to inquire if NEM is effective relative to oxygen-independent damage. Observations relative to survival, DNA synthesis, and DNA strand elongation resulting from the addition products to DNA when cells were exposed to near uv in the presence of psoralen were extended. (U.S.)

  3. Molecular biology in lung cancer

    Czech Academy of Sciences Publication Activity Database

    Kalina, I.; Biroš, Erik

    Poland: Institute of Nuclear Physics, 2002. s. 32. [NATO advanced research workshop. 23.06.2002-27.06.2002, Krakow - Poland] Institutional research plan: CEZ:AV0Z5039906 Keywords : cancer Subject RIV: FH - Neurology

  4. Biological atomism and cell theory.

    Science.gov (United States)

    Nicholson, Daniel J

    2010-09-01

    Biological atomism postulates that all life is composed of elementary and indivisible vital units. The activity of a living organism is thus conceived as the result of the activities and interactions of its elementary constituents, each of which individually already exhibits all the attributes proper to life. This paper surveys some of the key episodes in the history of biological atomism, and situates cell theory within this tradition. The atomistic foundations of cell theory are subsequently dissected and discussed, together with the theory's conceptual development and eventual consolidation. This paper then examines the major criticisms that have been waged against cell theory, and argues that these too can be interpreted through the prism of biological atomism as attempts to relocate the true biological atom away from the cell to a level of organization above or below it. Overall, biological atomism provides a useful perspective through which to examine the history and philosophy of cell theory, and it also opens up a new way of thinking about the epistemic decomposition of living organisms that significantly departs from the physicochemical reductionism of mechanistic biology. PMID:20934641

  5. Molecular biology of the cell

    CERN Document Server

    Alberts, Bruce; Lewis, Julian

    2000-01-01

    Molecular Biology of the Cell is the classic in-dept text reference in cell biology. By extracting the fundamental concepts from this enormous and ever-growing field, the authors tell the story of cell biology, and create a coherent framework through which non-expert readers may approach the subject. Written in clear and concise language, and beautifully illustrated, the book is enjoyable to read, and it provides a clear sense of the excitement of modern biology. Molecular Biology of the Cell sets forth the current understanding of cell biology (completely updated as of Autumn 2001), and it explores the intriguing implications and possibilities of the great deal that remains unknown. The hallmark features of previous editions continue in the Fourth Edition. The book is designed with a clean and open, single-column layout. The art program maintains a completely consistent format and style, and includes over 1,600 photographs, electron micrographs, and original drawings by the authors. Clear and concise concept...

  6. Systems biology and cancer, [Editorial

    OpenAIRE

    Soto, A M; Sonnenschein, C; Maini, P.K.

    2011-01-01

    The systems approach to complex biological problems has rapidly gained ground during the first decade of this century. There are several reasons for this development. An important one is that while the achievement of sequencing the complete human genome, and those of other species, has been of great benefit to fundamental science, for example in comparative genomics and evolutionary biology, it has not led to the expected quick and simple solutions to multifactorial diseases (2010). On the co...

  7. Syncytin is involved in breast cancer-endothelial cell fusions

    OpenAIRE

    Bjerregaard, Bolette; Holck, S.; Christensen, I. J.; Larsson, Lars-Inge

    2006-01-01

    Cancer cells can fuse spontaneously with normal host cells, including endothelial cells, and such fusions may strongly modulate the biological behaviour of tumors. However, the underlying mechanisms are unknown. We now show that human breast cancer cell lines and 63 out of 165 (38%) breast cancer specimens express syncytin, an endogenous retroviral envelope protein, previously implicated in fusions between placental trophoblast cells. Additionally, endothelial and cancer cells are shown to ex...

  8. Cyclin E Transgenic Mice: Discovery Tools for Lung Cancer Biology, Therapy, and Prevention

    OpenAIRE

    Freemantle, Sarah J.; Dmitrovsky, Ethan

    2010-01-01

    Lung cancer is the leading cause of cancer-related mortality in the United States and many other countries. This fact underscores the need for clinically relevant models to increase our understanding of lung cancer biology and to help design and implement preventive and more-effective therapeutic interventions for lung cancer. New murine transgenic models of non-small cell lung cancer (NSCLC) have been engineered for this purpose. In one such model, overexpression of the cell-cycle regulator ...

  9. Synthesis and biological evaluation of some novel triazole hybrids of curcumin mimics and their selective anticancer activity against breast and prostate cancer cell lines.

    Science.gov (United States)

    Mandalapu, Dhanaraju; Saini, Karan S; Gupta, Sonal; Sharma, Vikas; Yaseen Malik, Mohd; Chaturvedi, Swati; Bala, Veenu; Hamidullah; Thakur, Subhadra; Maikhuri, Jagdamba P; Wahajuddin, Muhammad; Konwar, Rituraj; Gupta, Gopal; Sharma, Vishnu Lal

    2016-09-01

    The anti-cancer property of curcumin, an active component of turmeric, is limited due to its poor solubility, stability and bioavailability. To enhance its efficacy, we designed a novel series of twenty-four monocarbonyl curcumin analogue-1,2,3-triazole conjugates and evaluated their anti-cancer activity towards endocrine related cancers. The new compounds (17-40) were synthesized through CuAAC click reaction and SAR analysis carried out. Out of these all, compound 17 showed most significant anti-cancer activity against prostate cancer cells with IC50 values of 8.8μM and 9.5μM in PC-3 and DU-145 cells, respectively. Another compound 26 showed significant anti-cancer activity against breast cancer cells with IC50 of 6μM, 10μM and 6.4μM in MCF-7, MDA-MB-231 and 4T1 cells, respectively while maintaining low toxicity towards non-cancer originated cell line, HEK-293. Compounds 17 and 26 arrested cell cycle and induced mitochondria-mediated apoptosis in cancer cells. Further, both of these compounds significantly down-regulated cell proliferation marker (PCNA), inhibited activation of cell survival protein (Akt phosphorylation), upregulated pro-apoptotic protein (Bax) and down-regulated anti-apoptotic protein (Bcl-2) in their respective cell lines. In addition, in vitro stability, solubility and plasma binding studies of the compounds 17 and 26 showed them to be metabolically stable. Thus, this study identified two new curcumin monocarbonyl-1,2,3-triazole conjugate compounds with more potent activity than curcumin against breast and prostate cancers. PMID:27496212

  10. Lipidomics Investigations in Cell Biology

    OpenAIRE

    YU, Yang

    2014-01-01

    Cell membrane is the biological barrier serving as both territorial defense and the communication hinge for the interior of cell from its surroundings. As building blocks of cellular membranes and also precursor for second messengers, a variety of lipids play essential roles in cellular membrane dynamics as well as important functions such as cell proliferation, apoptosis, signal transduction and membrane trafficking modulation. Lipidomics, representing the systematic and integrative studies ...

  11. Understanding the cancer stem cell

    OpenAIRE

    Bomken, S; Fišer, K; Heidenreich, O; Vormoor, J

    2010-01-01

    The last 15 years has seen an explosion of interest in the cancer stem cell (CSC). Although it was initially believed that only a rare population of stem cells are able to undergo self-renewing divisions and differentiate to form all populations within a malignancy, a recent work has shown that these cells may not be as rare as thought first, at least in some malignancies. Improved experimental models are beginning to uncover a less rigid structure to CSC biology, in which the concepts of fun...

  12. Understanding Cancer Prognosis

    Medline Plus

    Full Text Available ... Types Recurrent Cancer Common Cancer Types Bladder Cancer Breast Cancer Colorectal Cancer Kidney (Renal Cell) Cancer Leukemia Lung ... Biology Cancer Genomics Causes of Cancer Diagnosis Prevention Screening & Early Detection Treatment Cancer & Public Health Cancer Health ...

  13. Lung cancer-initiating cells: a novel target for cancer therapy

    OpenAIRE

    Morrison, Brian J.; Morris, John C.; Steel, Jason C

    2013-01-01

    Lung cancer is a major public health problem causing more deaths than any other cancer. A better understanding of the biology of this disease and improvements in treatment are greatly needed. Increasing evidence supports the concept that a rare and specialized population of cancer cells, so-called cancer-initiating cells with stem cell-like characteristics, is responsible for tumor growth, maintenance, and recurrence. Cancer-initiating cells also exhibit characteristics that render them resis...

  14. Metformin may function as anti-cancer agent via targeting cancer stem cells: the potential biological significance of tumor-associated miRNAs in breast and pancreatic cancers.

    Science.gov (United States)

    Bao, Bin; Azmi, Asfar S; Ali, Shadan; Zaiem, Feras; Sarkar, Fazlul H

    2014-06-01

    Metformin is one of the most used diabetic drugs for the management of type II diabetes mellitus (DM) in the world. Increased numbers of epidemiological and clinical studies have provided convincing evidence supporting the role of metformin in the development and progression of a variety of human tumors including breast and pancreatic cancer. Substantial pre-clinical evidence from in vitro and in vivo experimental studies strongly suggests that metformin has an anti-cancer activity mediated through the regulation of several cell signaling pathways including activation of AMP kinase (AMPK), and other direct and indirect mechanisms; however, the detailed mechanism(s) has not yet been fully understood. The concept of cancer stem cells (CSCs) has gained significant attention in recent years due its identification and defining its clinical implications in many different tumors including breast cancer and pancreatic cancer. In this review, we will discuss the protective role of metformin in the development of breast and pancreatic cancers. We will further discuss the role of metformin as an anti-cancer agent, which is in part mediated through targeting CSCs. Finally, we will discuss the potential role of metformin in the modulation of tumor-associated or CSC-associated microRNAs (miRNAs) as part of the novel mechanism of action of metformin in the development and progression of breast and pancreatic cancers. PMID:25333034

  15. Current dichotomy between traditional molecular biological and omic research in cancer biology and pharmacology.

    Science.gov (United States)

    Reinhold, William C

    2015-12-10

    There is currently a split within the cancer research community between traditional molecular biological hypothesis-driven and the more recent "omic" forms or research. While the molecular biological approach employs the tried and true single alteration-single response formulations of experimentation, the omic employs broad-based assay or sample collection approaches that generate large volumes of data. How to integrate the benefits of these two approaches in an efficient and productive fashion remains an outstanding issue. Ideally, one would merge the understandability, exactness, simplicity, and testability of the molecular biological approach, with the larger amounts of data, simultaneous consideration of multiple alterations, consideration of genes both of known interest along with the novel, cross-sample comparisons among cell lines and patient samples, and consideration of directed questions while simultaneously gaining exposure to the novel provided by the omic approach. While at the current time integration of the two disciplines remains problematic, attempts to do so are ongoing, and will be necessary for the understanding of the large cell line screens including the Developmental Therapeutics Program's NCI-60, the Broad Institute's Cancer Cell Line Encyclopedia, and the Wellcome Trust Sanger Institute's Cancer Genome Project, as well as the the Cancer Genome Atlas clinical samples project. Going forward there is significant benefit to be had from the integration of the molecular biological and the omic forms or research, with the desired goal being improved translational understanding and application. PMID:26677427

  16. Cancer Stem Cells, Cancer Cell Plasticity and Radiation Therapy

    OpenAIRE

    Vlashi, Erina; Pajonk, Frank

    2014-01-01

    Since the first prospective identification of cancer stem cells in solid cancers the cancer stem cell hypothesis has reemerged as a research topic of increasing interest. It postulates that solid cancers are organized hierarchically with a small number of cancer stem cells driving tumor growth, repopulation after injury and metastasis. They give rise to differentiated progeny, which lack these features. The model predicts that for any therapy to provide cure, all cancer stem cells have to be ...

  17. Cancer systems biology: signal processing for cancer research

    Institute of Scientific and Technical Information of China (English)

    Olli Yli-Harja; Antti Ylip(a)(a); Matti Nykter; Wei Zhang

    2011-01-01

    In this editorial we introduce the research paradigms of signal processing in the era of systems biology. Signal processing is a field of science traditionally focused on modeling electronic and communications systems, but recently it has turned to biological applications with astounding results. The essence of signal processing is to describe the natural world by mathematical models and then, based on these models, develop efficient computational tools for solving engineering problems. Here, we underline, with examples, the endless possibilities which arise when the battle-hardened tools of engineering are applied to solve the problems that have tormented cancer researchers. Based on this approach, a new field has emerged, called cancer systems biology. Despite its short history, cancer systems biology has already produced several success stories tackling previously impracticable problems. Perhaps most importantly, it has been accepted as an integral part of the major endeavors of cancer research, such as analyzing the genomic and epigenomic data produced by The Cancer Genome Atlas (TCGA) project. Finally, we show that signal processing and cancer research, two fields that are seemingly distant from each other, have merged into a field that is indeed more than the sum of its parts.

  18. Breast cancer stem cells

    Directory of Open Access Journals (Sweden)

    MatthewJNaylor

    2013-08-01

    Full Text Available Cancer metastasis, resistance to therapies and disease recurrence are significant hurdles to successful treatment of breast cancer. Identifying mechanisms by which cancer spreads, survives treatment regimes and regenerates more aggressive tumours are critical to improving patient survival. Substantial evidence gathered over the last 10 years suggests that breast cancer progression and recurrence is supported by cancer stem cells (CSCs. Understanding how CSCs form and how they contribute to the pathology of breast cancer will greatly aid the pursuit of novel therapies targeted at eliminating these cells. This review will summarise what is currently known about the origins of breast CSCs, their role in disease progression and ways in which they may be targeted therapeutically.

  19. The Implications of Cancer Stem Cells for Cancer Therapy

    Directory of Open Access Journals (Sweden)

    Wenjing Jiang

    2012-12-01

    Full Text Available Surgery, radiotherapy and chemotherapy are universally recognized as the most effective anti-cancer therapies. Despite significant advances directed towards elucidating molecular mechanisms and developing clinical trials, cancer still remains a major public health issue. Recent studies have showed that cancer stem cells (CSCs, a small subpopulation of tumor cells, can generate bulk populations of nontumorigenic cancer cell progeny through the self-renewal and differentiation processes. As CSCs are proposed to persist in tumors as a distinct population and cause relapse and metastasis by giving rise to new tumors, development of CSC-targeted therapeutic strategies holds new hope for improving survival and quality of life in patients with cancer. Therapeutic innovations will emerge from a better understanding of the biology and environment of CSCs, which, however, are largely unexplored. This review summarizes the characteristics, evidences and development of CSCs, as well as implications and challenges for cancer treatment.

  20. 人乳腺癌细胞微球体生物学特性研究%Study on the biological characteristics of human breast cancer cell mammospheres

    Institute of Scientific and Technical Information of China (English)

    范原铭; 侯婧; 董宁; 王强; 顾敏

    2015-01-01

    目的:研究人乳腺癌细胞微球体(MSs)的生物学特性,建立乳腺癌干细胞实验模型。方法无血清悬浮培养人乳腺癌MCF‐7细胞(MCF‐7组),并获取MSs(MSs组)。利用细胞划痕实验、transwell实验及动物成瘤实验检测MSs在细胞迁移、侵袭性生长及体外成瘤等方面的生物学特性。结果细胞划痕实验提示:MSs组划痕带可在48 h后愈合,而MCF‐7组划痕带在48 h后未能愈合;transwell实验提示MSs组中可见到(76.24±0.35)个细胞通过生物膜,而MCF‐7细胞组中为(17.38±0.18)个(P<0.05);动物成瘤实验提示:MSs在成瘤速度及移植瘤体积方面均强于MCF‐7细胞。结论 MSs具有极强的迁移、侵袭性生长及动物体内成瘤的能力,可作为实验模型应用于乳腺癌干细胞相关研究中。%Objective To study the biological characteristics of the human breast cancer cell mammospheres (MSs) ,and con‐struct breast cancer stem cell experiment model .Methods MCF‐7 cells were cultured in the serum‐free media supplemented with growth factors (the MCF‐7 group) ,and the MSs was collected (the MSs group) .The migration ,invasive and animal tumor forma‐tion abilities of MSs were detected by wound healing ,transwell invasive assay and animal tumor formation test .Results The wound line of MSs healed after 48 hours ,but the line of MCF‐7cells could not heal after 48 h .The number of the cells going through the membrane in MSs group was (76 .24 ± 0 .35) ,and the number in MCF‐7cells was (17 .38 ± 0 .18)(P<0 .05) .MSs had stronger ani‐mal tumor formation ability than MCF‐7 cells .Conclusion MSs have stronger abilities in migration ,invasive and animal tumor for‐mation ,and could be used in the studies of breast cancer stem cell as experimental model .

  1. Physical View on the Interactions Between Cancer Cells and the Endothelial Cell Lining During Cancer Cell Transmigration and Invasion

    Science.gov (United States)

    Mierke, Claudia T.

    There exist many reviews on the biological and biochemical interactions of cancer cells and endothelial cells during the transmigration and tissue invasion of cancer cells. For the malignant progression of cancer, the ability to metastasize is a prerequisite. In particular, this means that certain cancer cells possess the property to migrate through the endothelial lining into blood or lymph vessels, and are possibly able to transmigrate through the endothelial lining into the connective tissue and follow up their invasion path in the targeted tissue. On the molecular and biochemical level the transmigration and invasion steps are well-defined, but these signal transduction pathways are not yet clear and less understood in regards to the biophysical aspects of these processes. To functionally characterize the malignant transformation of neoplasms and subsequently reveal the underlying pathway(s) and cellular properties, which help cancer cells to facilitate cancer progression, the biomechanical properties of cancer cells and their microenvironment come into focus in the physics-of-cancer driven view on the metastasis process of cancers. Hallmarks for cancer progression have been proposed, but they still lack the inclusion of specific biomechanical properties of cancer cells and interacting surrounding endothelial cells of blood or lymph vessels. As a cancer cell is embedded in a special environment, the mechanical properties of the extracellular matrix also cannot be neglected. Therefore, in this review it is proposed that a novel hallmark of cancer that is still elusive in classical tumor biological reviews should be included, dealing with the aspect of physics in cancer disease such as the natural selection of an aggressive (highly invasive) subtype of cancer cells displaying a certain adhesion or chemokine receptor on their cell surface. Today, the physical aspects can be analyzed by using state-of-the-art biophysical methods. Thus, this review will present

  2. Characterization of the DNA methylation patterns of chemosensitive and chemoresistant human cancer cells: Biological and clinical impact

    OpenAIRE

    Moutinho, Cátia

    2014-01-01

    Tesi realitzada a l'Institut d'Investigació Biomèdica de Bellvitge (IDIBELL) Although chemotherapeutic drugs are widely used in order to improve the cancer outcome, drug resistance remain the most unpredictable factor affecting chemotherapy and a major impediment to successful patient’s treatment. Understanding the cellular mechanisms leading to chemoresistance may dramatically impact on the way chemotherapeutic drugs are used. Then, it would allow selecting the most suitable personalized ...

  3. Cell-based delivery of oncolytic viruses: a new strategic alliance for a biological strike against cancer.

    Science.gov (United States)

    Power, Anthony T; Bell, John C

    2007-04-01

    Recent years have seen tremendous advances in the development of exquisitely targeted replicating virotherapeutics that can safely destroy malignant cells. Despite this promise, clinical advancement of this powerful and unique approach has been hindered by vulnerability to host defenses and inefficient systemic delivery. However, it now appears that delivery of oncolytic viruses within carrier cells may offer one solution to this critical problem. In this review, we compare the advantages and limitations of the numerous cell lineages that have been investigated as delivery platforms for viral therapeutics, and discuss examples showing how combined cell-virus biotherapeutics can be used to achieve synergistic gains in antitumor activity. Finally, we highlight avenues for future preclinical research that might be taken in order to refine cell-virus biotherapeutics in preparation for human trials. PMID:17264852

  4. Cell biology of fat storage.

    Science.gov (United States)

    Cohen, Paul; Spiegelman, Bruce M

    2016-08-15

    The worldwide epidemic of obesity and type 2 diabetes has greatly increased interest in the biology and physiology of adipose tissues. Adipose (fat) cells are specialized for the storage of energy in the form of triglycerides, but research in the last few decades has shown that fat cells also play a critical role in sensing and responding to changes in systemic energy balance. White fat cells secrete important hormone-like molecules such as leptin, adiponectin, and adipsin to influence processes such as food intake, insulin sensitivity, and insulin secretion. Brown fat, on the other hand, dissipates chemical energy in the form of heat, thereby defending against hypothermia, obesity, and diabetes. It is now appreciated that there are two distinct types of thermogenic fat cells, termed brown and beige adipocytes. In addition to these distinct properties of fat cells, adipocytes exist within adipose tissue, where they are in dynamic communication with immune cells and closely influenced by innervation and blood supply. This review is intended to serve as an introduction to adipose cell biology and to familiarize the reader with how these cell types play a role in metabolic disease and, perhaps, as targets for therapeutic development. PMID:27528697

  5. Fingerprints in cancer cells

    International Nuclear Information System (INIS)

    Gene research has shown that factors causing cancer, or carcinogens, may leave marks typical of each particular carcinogen (fingerprints) in the genotype of the cell. Radiation, for instance, may leave such fingerprints in a cancer cell. In particular, the discovery of a gene called p53 has yielded much new information on fingerprints. It has been discovered, for example, that toxic fungus and UV-radiation each leave fingerprints in the p53 gene. Based on the detection of fingerprints, it may be possible in the future to tell a cancer patient what factor had trigged the maglinancy

  6. Which Is the Optimal Biologically Effective Dose of Stereotactic Body Radiotherapy for Stage I Non–Small-Cell Lung Cancer? A Meta-Analysis

    International Nuclear Information System (INIS)

    Purpose: To assess the relationship between biologically effective dose (BED) and efficacy of stereotactic body radiation therapy (SBRT) and to explore the optimal BED range for Stage I non–small-cell lung cancer (NSCLC). Methods and Materials: Eligible studies were identified on Medline, Embase, the Cochrane Library, and the proceedings of annual meetings through June 2010. According to the quartile of included studies, BED was divided into four dose groups: low (146 Gy). To obtain pooled estimates of overall survival (OS), cancer-specific survival (CSS), and local control rate (LCR), data were combined in a random effect model. Pooled estimates were corrected for the percentage of small tumors (<3 cm). Results: Thirty-four observational studies with a total of 2,587 patients were included in the meta-analysis. Corrected pooled estimates of 2- or 3-year OS in the medium BED (76.1%, 63.5%) or the medium to high BED (68.3%, 63.2%) groups were higher than in the low (62.3%, 51.9%) or high groups (55.9%, 49.5%), respectively (p ≤ 0.004). Corrected 3-year CSS in the medium (79.5%), medium to high (80.6%), and high groups (90.0%) were higher than in the low group (70.1%, p = 0.016, 0.018, 0.001, respectively). Conclusion: The OS for the medium or medium to high BED groups were higher than those for the low or high BED group for SBRT in Stage I NSCLC. The medium or medium to high BED (range, 83.2 146 Gy) for SBRT may currently be more beneficial and reasonable in Stage I NSCLC.

  7. Prostate cancer stem cells

    OpenAIRE

    Tu, Shi-Ming; Lin, Sue-Hwa

    2011-01-01

    Stem cells have long been implicated in prostate glandular formation. The prostate undergoes regression after androgen deprivation and regeneration after testosterone replacement. Regenerative studies suggest that these cells are found in the proximal ducts and basal layer of the prostate. Many characteristics of prostate cancer indicate that it originates from stem cells. For example, the putative AR− status of prostate stem cells renders them inherently insensitive to androgen blockade ther...

  8. A Systems Biology View of Cancer

    OpenAIRE

    Laubenbacher, Reinhard; Hower, Valerie; Jarrah, Abdul; Torti, Suzy V.; Shulaev, Vladimir; Mendes, Pedro; Torti, Frank M.; Akman, Steven

    2009-01-01

    In order to understand how a cancer cell is functionally different from a normal cell it is necessary to assess the complex network of pathways involving gene regulation, signaling, and cell metabolism, and the alterations in its dynamics caused by the several different types of mutations leading to malignancy. Since the network is typically complex, with multiple connections between pathways and important feedback loops, it is crucial to represent it in the form of a computational model that...

  9. Stem cell biology meets systems biology

    OpenAIRE

    Roeder, I.; Radtke, F.

    2009-01-01

    Stem cells and their descendents are the building blocks of life. How stem cell populations guarantee their maintenance and/or self-renewal, and how individual stem cells decide to transit from one cell stage to another to generate different cell types are long-standing and fascinating questions in the field. Here, we review the discussions that took place at a recent EMBO conference in Cambridge, UK, in which these questions were placed in the context of the latest advances in stem cell biol...

  10. Cancer tissue engineering - new perspectives in understanding the biology of solid tumours - a critical review

    NARCIS (Netherlands)

    Ricci, C.; Moroni, L.; Danti, S.

    2013-01-01

    Understanding cancer biology is a major challenge of this century. The recent insight about carcinogenesis mechanisms, including the role exerted by the tumour microenvironment and cancer stem cells in chemoresistance, relapse and metastases, has made it self-evident that only new cancer models, wit

  11. Biological fuel cells and their applications

    OpenAIRE

    Shukla, AK; Suresh, P; Berchmans, S; Rajendran, A.

    2004-01-01

    One type of genuine fuel cell that does hold promise in the long-term is the biological fuel cell. Unlike conventional fuel cells, which employ hydrogen, ethanol and methanol as fuel, biological fuel cells use organic products produced by metabolic processes or use organic electron donors utilized in the growth processes as fuels for current generation. A distinctive feature of biological fuel cells is that the electrode reactions are controlled by biocatalysts, i.e. the biological redox-reac...

  12. Cancer Stem Cells in Pancreatic Cancer

    International Nuclear Information System (INIS)

    Pancreatic cancer is an aggressive malignant solid tumor well-known by early metastasis, local invasion, resistance to standard chemo- and radiotherapy and poor prognosis. Increasing evidence indicates that pancreatic cancer is initiated and propagated by cancer stem cells (CSCs). Here we review the current research results regarding CSCs in pancreatic cancer and discuss the different markers identifying pancreatic CSCs. This review will focus on metastasis, microRNA regulation and anti-CSC therapy in pancreatic cancer

  13. Stochastic processes in cell biology

    CERN Document Server

    Bressloff, Paul C

    2014-01-01

    This book develops the theory of continuous and discrete stochastic processes within the context of cell biology.  A wide range of biological topics are covered including normal and anomalous diffusion in complex cellular environments, stochastic ion channels and excitable systems, stochastic calcium signaling, molecular motors, intracellular transport, signal transduction, bacterial chemotaxis, robustness in gene networks, genetic switches and oscillators, cell polarization, polymerization, cellular length control, and branching processes. The book also provides a pedagogical introduction to the theory of stochastic process – Fokker Planck equations, stochastic differential equations, master equations and jump Markov processes, diffusion approximations and the system size expansion, first passage time problems, stochastic hybrid systems, reaction-diffusion equations, exclusion processes, WKB methods, martingales and branching processes, stochastic calculus, and numerical methods.   This text is primarily...

  14. Biological markers of invasive breast cancer.

    Science.gov (United States)

    Matsumoto, Akiko; Jinno, Hiromitsu; Ando, Tomofumi; Fujii, Taku; Nakamura, Tetsuya; Saito, Junichi; Takahashi, Maiko; Hayashida, Tetsu; Kitagawa, Yuko

    2016-02-01

    Biological markers for breast cancer are biomolecules that result from cancer-related processes and are associated with particular clinical outcomes; they thus help predict responses to therapy. In recent years, gene expression profiling has made the molecular classification of breast cancer possible. Classification of breast cancer by immunohistochemical expression of estrogen receptor, progesterone receptor, human epidermal growth factor receptor 2 and Ki-67 is standard practice for clinical decision-making. Assessments of hormone receptor expression and human epidermal growth factor receptor 2 overexpression help estimate benefits from targeted therapies and have greatly improved prognoses for women with these breast cancer types. Although Ki-67 positivity is associated with an adverse outcome, its clear identification is an aid to optimal disease management. Standardization of testing methodology to minimize inter-laboratory measurement variations is a remaining issue. Multi-gene assays provide prognostic information and identify those most likely to benefit from systemic chemotherapy. Incorporating molecular profiles with conventional pathological classification would be more precise, and could enhance the clinical development of personalized therapy in breast cancer. PMID:26486826

  15. The redox biology network in cancer pathophysiology and therapeutics

    Directory of Open Access Journals (Sweden)

    Gina Manda

    2015-08-01

    Full Text Available The review pinpoints operational concepts related to the redox biology network applied to the pathophysiology and therapeutics of solid tumors. A sophisticated network of intrinsic and extrinsic cues, integrated in the tumor niche, drives tumorigenesis and tumor progression. Critical mutations and distorted redox signaling pathways orchestrate pathologic events inside cancer cells, resulting in resistance to stress and death signals, aberrant proliferation and efficient repair mechanisms. Additionally, the complex inter-cellular crosstalk within the tumor niche, mediated by cytokines, redox-sensitive danger signals (HMGB1 and exosomes, under the pressure of multiple stresses (oxidative, inflammatory, metabolic, greatly contributes to the malignant phenotype. The tumor-associated inflammatory stress and its suppressive action on the anti-tumor immune response are highlighted. We further emphasize that ROS may act either as supporter or enemy of cancer cells, depending on the context. Oxidative stress-based therapies, such as radiotherapy and photodynamic therapy, take advantage of the cytotoxic face of ROS for killing tumor cells by a non-physiologically sudden, localized and intense oxidative burst. The type of tumor cell death elicited by these therapies is discussed. Therapy outcome depends on the differential sensitivity to oxidative stress of particular tumor cells, such as cancer stem cells, and therefore co-therapies that transiently down-regulate their intrinsic antioxidant system hold great promise. We draw attention on the consequences of the damage signals delivered by oxidative stress-injured cells to neighboring and distant cells, and emphasize the benefits of therapeutically triggered immunologic cell death in metastatic cancer. An integrative approach should be applied when designing therapeutic strategies in cancer, taking into consideration the mutational, metabolic, inflammatory and oxidative status of tumor cells, cellular

  16. The Study on Newly Developed McAb NJ001 Specific to Non-Small Cell Lung Cancer and Its Biological Characteristics

    OpenAIRE

    Pan, Shiyang; WANG, FANG; Huang, Peijun; Xu, Ting; Zhang, Lixia; Xu, Jian; Li, Qing; Xia, Wenying; Sun, Ruihong; Huang, Lei; Peng, Ying; Qin, Xuejun; Shu, Yongqian; Hu, Zhibin; Shen, Hongbing

    2012-01-01

    Monoclonal antibody (McAb) is the key tool for cancer immunodiagnosis and immunotherapy. McAb-based immunotherapy that targets tumor antigens has had great achivement. In this study, a cell clone which kept secreting high-titer IgG1-type McAb named NJ001 against human non-small cell lung cancer (NSCLC) cells was obtained. The titer of purified NJ001 was 2×106. The antigen named SP70 of NSCLC specifically identified by NJ001 was proved to be a protein with the relative molecular mass (Mr) of 7...

  17. Cancer Stem Cells

    OpenAIRE

    Aurelio Lorico; Eric Deutsch; Bo Lu; Shih-Hwa Chiou

    2011-01-01

    Cancer Stem Cells (CSCs) are a small subpopulation of cells within tumors with capabilities of self-renewal, differentiation, and tumorigenicity when transplanted into an animal host. A number of cell surface markers such as CD44, CD24, and CD133 are often used to identify and enrich CSCs. A regulatory network consisting of microRNAs and Wnt/β-catenin, Notch, and Hedgehog signaling pathways controls the CSC properties. The clinical relevance of CSCs has been strengthened by emerging evidence,...

  18. The biological difference between CD13+CD133+ and CD13¬CD133¬liver cancer cells and its clinical significance

    OpenAIRE

    Shi-long JIN; Zhong-rong HUANG; Chen, Hua; Tian-wu YU; Cao, Hong; Yun-quan LONG; Zhou, Jian; Li, He; Yi GOU; Li, Yuan; Liao, Juan

    2013-01-01

    Objective To compare the biological difference between CD13+CD133+ and CD13-CD133- hepatocellular carcinoma (HCC) cells in HuH7 cell line and its clinical significance. Methods The status of proliferation, phase of the cell cycle, tumor formation in vivo, differentiation, and their chemoresistance to 5-FU and pirarubicin of CD13+CD133+ and CD13-CD133-HCC cells were studied to analyze the clinical implication of CD13+CD133+HCC cell subset. Results The proliferation rate of CD13+CD133+HCC cells...

  19. A historical discourse analysis of the cancerous and non-cancerous body in secondary biology textbooks

    Science.gov (United States)

    Bowers, Neil Thomas

    This dissertation applies the archeological concepts developed by Michel Foucault to a study of thirteen biology textbooks (1993-2004) in order to develop an understanding of 'purchased truths' concerning cancer. This study focuses on the construction of the health/illness dialogue concerning cancer within the textbooks and not the meaning that the individual makes from reading the text; as such this study concerns itself with social truths rather than the search for an individual awareness of names, dates, or places. This study investigates the practices that allow the creation of dialogues that are inserted into a biology textbook and looks at how discursive formations create the 'truth regime' from which the biology textbook is said to speak. Using the Foucaultian themes of 'event', 'emergence', 'enunciation', and 'exteriority' a new reading of topics concerning cancer emerge from biology textbooks. Cancer is a disease that will impact the lives of countless individuals but coverage devoted to the pathology of cancer in secondary biology textbooks is very limited and no study textbook devoted a whole chapter to the discussion of cancer. There is an identified reduction in the number of pages and depth of coverage devoted to cancer in the newer biology texts compared to the older texts. Humans are pictured more than plants or animals in presentations concerning cancer with emphasis being placed on the digitalization of human cells via the scanning electron microscope. When the whole body is presented it is seldom located within the technology of disease diagnosis and treatment but rather is posed for specific social control. Just as each digitized picture of the cancerous cell in the texts is used to create a story so too are the pictures of the whole body in action. Possible story lines offered by the publishing houses concerning the reaction of the body to cancer are shown to intermingle with risk factor analysis to project a sense of Foucaultian

  20. Thyroid stem cells: lessons from normal development and thyroid cancer

    OpenAIRE

    Thomas, Dolly; Friedman, Susan; Lin, Reigh-Yi

    2008-01-01

    Ongoing advances in stem cell research have opened new avenues for therapy for many human disorders. Until recently, however, thyroid stem cells have been relatively understudied. Here, we review what is known about thyroid stem cells and explore their utility as models of normal and malignant biological development. We also discuss the cellular origin of thyroid cancer stem cells and explore the clinical implications of cancer stem cells in the thyroid gland. Since thyroid cancer is the most...

  1. Selenium Metabolism in Cancer Cells: The Combined Application of XAS and XFM Techniques to the Problem of Selenium Speciation in Biological Systems

    OpenAIRE

    Harris, Hugh H; Stefan Vogt; Witting, Paul K.; Aitken, Jade B.; Lydia Finney; Weekley, Claire M.

    2013-01-01

    Determining the speciation of selenium in vivo is crucial to understanding the biological activity of this essential element, which is a popular dietary supplement due to its anti-cancer properties. Hyphenated techniques that combine separation and detection methods are traditionally and effectively used in selenium speciation analysis, but require extensive sample preparation that may affect speciation. Synchrotron-based X-ray absorption and fluorescence techniques offer an alternative appro...

  2. Laboratory of Cell and Molecular Biology

    Data.gov (United States)

    Federal Laboratory Consortium — The Laboratory of Cell and Molecular Biology investigates the organization, compartmentalization, and biochemistry of eukaryotic cells and the pathology associated...

  3. Atomic force microscopy in cell biology

    Institute of Scientific and Technical Information of China (English)

    LU Zhexue; ZHANG Zhiling; PANG Daiwen

    2005-01-01

    The history, characteristic, operation modes and coupling techniques of atomic force microscopy (AFM) are introduced. Then the application in cell biology is reviewed in four aspects: cell immobilization methods, cell imaging, force spectrum study and cell manipulation. And the prospect of AFM application in cell biology is discussed.

  4. Stem Cells and Cancer; Celulas madre y cancer

    Energy Technology Data Exchange (ETDEWEB)

    Segrelles, C.; Paraminio, J. M.; Lorz, C.

    2014-04-01

    Stem cell research has thrived over the last years due to their therapeutic and regenerative potential. Scientific breakthroughs in the field are immediately translated from the scientific journals to the mass media, which is not surprising as the characterisation of the molecular mechanisms that regulate the biology of stem cells is crucial for the treatment of degenerative and cardiovascular diseases, as well as cancer. In the Molecular Oncology Unit at Ciemat we work to unravel the role of cancer stem cells in tumour development, and to find new antitumor therapies. (Author)

  5. Clinical perspectives of cancer stem cell research in radiation oncology

    International Nuclear Information System (INIS)

    Radiotherapy has a proven potential to eradicate cancer stem cells which is reflected by its curative potential in many cancer types. Considerable progress has been made in identification and biological characterisation of cancer stem cells during the past years. Recent biological findings indicate significant inter- and intratumoural and functional heterogeneity of cancer stem cells and lead to more complex models which have potential implications for radiobiology and radiotherapy. Clinical evidence is emerging that biomarkers of cancer stem cells may be prognostic for the outcome of radiotherapy in some tumour entities. Perspectives of cancer stem cell based research for radiotherapy reviewed here include their radioresistance compared to the mass of non-cancer stem cells which form the bulk of all tumour cells, implications for image- and non-image based predictive bio-assays of the outcome of radiotherapy and a combination of novel systemic treatments with radiotherapy

  6. Extragonadal Germ Cell Cancer (EGC)

    Science.gov (United States)

    ... Testicular Cancer Resource Center Extragonadal Germ Cell Cancer (EGC) 95% of all testicular tumors are germ cell ... seen in young adults. Patients with mediastinal nonseminomatous EGC are typically classed as poor risk patients because ...

  7. Epidemiology and biology of cervical cancer.

    Science.gov (United States)

    Schoell, W M; Janicek, M F; Mirhashemi, R

    1999-01-01

    Worldwide, cancer of the cervix is the second leading cause of cancer death in women: each year, an estimated 500,000 cases are newly diagnosed. Among populations, there are large differences in incidence rates of invasive cervical cancer: these reflect the influence of environmental factors, screening Papanicolaou (Pap) tests, and treatment of pre-invasive lesions. The high-risk human papillomavirus (HPV) subtypes 16, 18, 31, 33, and 51 have been recovered from more than 95% of cervical cancers. We have made great strides in understanding the molecular mechanism of oncogenesis of this virus, focusing on the action of the E6 and E7 viral oncoproteins. These oncoproteins function by inactivating cell cycle regulators p53 and retinoblastoma (Rb), thus providing the initial event in progression to malignancy. Cervical cancers develop from precursor lesions, which are termed squamous intraepithelial lesions (SIL) and are graded as high or low, depending on the degree of disruption of epithelial differentiation. Viral production occurs in low-grade lesions and is restricted to basal cells. In carcinomas, viral DNA is found integrated into the host genome, but no viral production is seen. The well-defined pre-invasive stages, as well as the viral factors involved at the molecular level, make cervical carcinoma a good model for investigating immune therapeutic alternatives or adjuvants to standard treatments. PMID:10225296

  8. Chemokine receptors in cancer metastasis and cancer cell-derived chemokines in host immune response.

    Science.gov (United States)

    Koizumi, Keiichi; Hojo, Shozo; Akashi, Takuya; Yasumoto, Kazuo; Saiki, Ikuo

    2007-11-01

    The chemotactic cytokines called chemokines are a superfamily of small secreted cytokines that were initially characterized through their ability to prompt the migration of leukocytes. Attention has been focused on the chemokine receptors expressed on cancer cells because cancer cell migration and metastasis show similarities to leukocyte trafficking. CXC chemokine receptor 4 (CXCR4) was first investigated as a chemokine receptor that is associated with lung metastasis of breast cancers. Recently, CXCR4 was reported to be a key molecule in the formation of peritoneal carcinomatosis in gastric cancer. In the present review, we highlight current knowledge about the role of CXCR4 in cancer metastases. In contrast to chemokine receptors expressed on cancer cells, little is known about the roles of cancer cell-derived chemokines. Cancer tissue consists of both cancer cells and various stromal cells, and leukocytes that infiltrate into cancer are of particular importance in cancer progression. Although colorectal cancer invasion is regulated by the chemokine CCL9-induced infiltration of immature myeloid cells into cancer, high-level expression of cancer cell-derived chemokine CXCL16 increases infiltrating CD8(+) and CD4(+) T cells into cancer tissues, and correlates with a good prognosis. We discuss the conflicting biological effects of cancer cell-derived chemokines on cancer progression, using CCL9 and CXCL16 as examples. PMID:17894551

  9. Cancer stem cells in prostate cancer

    OpenAIRE

    Moltzahn, Felix; Thalmann, George N

    2013-01-01

    Prostate cancer (P-Ca) remains a leading cause of cancer-related death in men. Lately, increasing evidence for a hierarchically organized cancer stem cell (CSC) model emerged for different tumors entities, including P-Ca. CSCs are defined by several characteristics including self-renewal, pluripotency and tumorigenicity and are thought to be responsible for tumor recurrence, metastasis and cancer related death. In this review we discuss the recent research in the field of CSCs, its limitation...

  10. Cancer Stem Cells in Pancreatic Cancer

    OpenAIRE

    Karl-Walter Jauch; Hendrik Seeliger; Hanno Niess; Qi Bao; Andrea Renner; Yue Zhao; Bruns, Christiane J.

    2010-01-01

    Pancreatic cancer is an aggressive malignant solid tumor well-known by early metastasis, local invasion, resistance to standard chemo- and radiotherapy and poor prognosis. Increasing evidence indicates that pancreatic cancer is initiated and propagated by cancer stem cells (CSCs). Here we review the current research results regarding CSCs in pancreatic cancer and discuss the different markers identifying pancreatic CSCs. This review will focus on metastasis, microRNA regulation and anti-CSC t...

  11. Invasive cancer cells and metastasis

    Science.gov (United States)

    Mierke, Claudia Tanja

    2013-12-01

    The physics of cancer is a relatively new emerging field of cancer research. In the last decade it has become a focus of biophysical research as well as becoming a novel focus for classical cancer research. This special section of Physical Biology focusing on invasive cancer cells and metastasis (physical oncology) will give greater insight into the different subfields where physical approaches are being applied to cancer research. This focus on the physical aspects of cancer is necessary because novel approaches in the field of genomics and proteomics have not altered the field of cancer research dramatically, due to the fact that few breakthroughs have been made. It is still not understood why some primary tumors metastasize and thus have a worse outcome compared to others that do not metastasize. As biophysicists, we and others suggest that the mechanical properties of the cancer cells, which possess the ability to transmigrate, are quite different compared to non-metastatic and non-invasive cancer cells. Furthermore, we hypothesize that these cancer cells undergo a selection process within the primary tumor that enables them to weaken their cell-cell adhesions and to alter their cell-matrix adhesions in order to be able to cross the outermost boundary of the primary tumor, as well as the surrounding basement membrane, and to invade the connective tissue. This prerequisite may also help the cancer cells to enter blood or lymph vessels, get transported with the vessel flow and form secondary tumors either within the vessel, directly on the endothelium, or in a different organ after crossing the endothelial lining a second time. This special section begins with a paper by Mark F Coughlin and Jeffrey J Fredberg on the changes in cytoskeletal dynamics and nonlinear rheology due to the metastatic capability of cancer cells from different cancer tissue types such as skin, bladder, prostate and kidney [1]. The hypothesis was that the metastatic outcome is impacted by

  12. Cancer Stem Cell Hierarchy in Glioblastoma Multiforme.

    Science.gov (United States)

    Bradshaw, Amy; Wickremsekera, Agadha; Tan, Swee T; Peng, Lifeng; Davis, Paul F; Itinteang, Tinte

    2016-01-01

    Glioblastoma multiforme (GBM), an aggressive tumor that typically exhibits treatment failure with high mortality rates, is associated with the presence of cancer stem cells (CSCs) within the tumor. CSCs possess the ability for perpetual self-renewal and proliferation, producing downstream progenitor cells that drive tumor growth. Studies of many cancer types have identified CSCs using specific markers, but it is still unclear as to where in the stem cell hierarchy these markers fall. This is compounded further by the presence of multiple GBM and glioblastoma cancer stem cell subtypes, making investigation and establishment of a universal treatment difficult. This review examines the current knowledge on the CSC markers SALL4, OCT-4, SOX2, STAT3, NANOG, c-Myc, KLF4, CD133, CD44, nestin, and glial fibrillary acidic protein, specifically focusing on their use and validity in GBM research and how they may be utilized for investigations into GBM's cancer biology. PMID:27148537

  13. Cancer Stem Cell Hierarchy in Glioblastoma Multiforme

    Science.gov (United States)

    Bradshaw, Amy; Wickremsekera, Agadha; Tan, Swee T.; Peng, Lifeng; Davis, Paul F.; Itinteang, Tinte

    2016-01-01

    Glioblastoma multiforme (GBM), an aggressive tumor that typically exhibits treatment failure with high mortality rates, is associated with the presence of cancer stem cells (CSCs) within the tumor. CSCs possess the ability for perpetual self-renewal and proliferation, producing downstream progenitor cells that drive tumor growth. Studies of many cancer types have identified CSCs using specific markers, but it is still unclear as to where in the stem cell hierarchy these markers fall. This is compounded further by the presence of multiple GBM and glioblastoma cancer stem cell subtypes, making investigation and establishment of a universal treatment difficult. This review examines the current knowledge on the CSC markers SALL4, OCT-4, SOX2, STAT3, NANOG, c-Myc, KLF4, CD133, CD44, nestin, and glial fibrillary acidic protein, specifically focusing on their use and validity in GBM research and how they may be utilized for investigations into GBM’s cancer biology.

  14. Immunolocalisation of members of the polypeptide N-acetylgalactosaminyl transferase (ppGalNAc-T) family is consistent with biologically relevant altered cell surface glycosylation in breast cancer

    DEFF Research Database (Denmark)

    Brooks, Susan A; Carter, Tracey M; Bennett, Eric P;

    2007-01-01

    An extensive family of UDP-N-alpha-d-galactosamine: polypeptide N-acetylgalactosaminyltransferases (polypeptide N-acetylgalactosaminyltransferases, ppGalNAc-T's) catalyse the attachment of the first N-acetylgalactosamine (GalNAc) monosaccharide to the polypeptide at the initiation of O......-linked glycosylation of proteins. Some members of the family are broadly expressed while others are more restricted in their distribution, their expression and activity being confined to certain cells or tissues, being associated with physiological states or differentiation. Their careful regulation, which is not well...... the ppGalNAc-T family, ppGalNAc-T1, -T2, -T3, -T4 and -T6 in a range of breast cell lines. The cells were chosen to represent a range of phenotypes from 'normal'/benign (HMT 3,522), primary, non-metastatic breast cancer (BT 474), to aggressive, metastatic breast cancer (ZR75-1, T47D, MCF-7, DU 4...

  15. Cancer stem cell subsets and their relationships

    OpenAIRE

    Pan Yi-Fei; Yang Han; Chen Chong; Liu Hai-Guang; Zhang Xiao-Hua

    2011-01-01

    Abstract Emerging evidence suggests that cancer stem cells account for the initiation and progression of cancer. While many types of cancer stem cells with specific markers have been isolated and identified, a variety of differences among them began to be appreciated. Cancer stem cells are hierarchical populations that consist of precancerous stem cells, primary cancer stem cells, migrating cancer stem cells and chemoradioresistant cancer stem cells, playing different roles in cancer initiati...

  16. Cinnamaldehyde affects the biological behavior of human colorectal cancer cells and induces apoptosis via inhibition of the PI3K/Akt signaling pathway.

    Science.gov (United States)

    Li, Jiepin; Teng, Yuhao; Liu, Shenlin; Wang, Zifan; Chen, Yan; Zhang, Yingying; Xi, Songyang; Xu, Song; Wang, Ruiping; Zou, Xi

    2016-03-01

    Cinnamaldehyde (CA) is a bioactive compound isolated from the stem bark of Cinnamomum cassia, that has been identified as an antiproliferative substance with pro-apoptotic effects on various cancer cell lines in vitro. In the present study, the effects of CA on human colon cancer cells were investigated at both the molecular and cellular levels. Three types of colorectal cancer cells at various stages of differentiation and invasive ability (SW480, HCT116 and LoVo) were treated with CA at final concentrations of 20, 40 and 80 µg/ml for 24 h. Compared with the control group, the proliferation inhibition rate of the human colorectal cancer cells following treatment with CA increased in a dose- and time-dependent manner. The invasion and adhesion abilities of the cells were significantly inhibited as indicated by Transwell and cell-matrix adhesion assays. Meanwhile, CA also upregulated the expression of E-cadherin and downregulated the expression of matrix metalloproteinase-2 (MMP-2) and MMP-9. CA also elevated the apoptotic rate. The levels of pro-apoptotic genes were upregulated while the levels of apoptosis inhibitory genes were decreased which further confirmed the pro-apoptotic effect of CA. In order to explore the mechanism of CA-induced apoptosis, insulin-like growth factor-1 (IGF-1) and PI3K inhibitor (LY294002) were used to regulate the phosphoinositide 3-kinase (PI3K)/AKT pathway. The transcription activity of PI3K/AKT was markedly inhibited by CA, as well as IGF-1 which functions as an anti-apoptotic factor. In conclusion, CA has the potential to be developed as a new antitumor drug. The mechanisms of action involve the regulation of expression of genes involved in apoptosis, invasion and adhesion via inhibition of the PI3K/Akt signaling pathway. PMID:26677144

  17. Hypoxia regulates stemness of breast cancer MDA-MB-231 cells

    OpenAIRE

    Xie, Jing; Xiao, Yong; Zhu, Xiao-Yan; Ning, Zhou-yu; Xu, Hai-fan; Wu, Hui-Min

    2016-01-01

    Human breast cancers include cancer stem cell populations as well as non-tumorigenic cancer cells. Breast cancer stem cells possess self-renewal capability and thus are the root cause of recurrence and metastasis of malignant tumors. Hypoxia is a fundamental pathological feature of solid tumor tissues and exerts a wide range of effects on the biological behavior of cancer cells. However, there is little information on the role of hypoxia in modulating the stemness of breast cancer cells. In t...

  18. Tracking metastatic breast cancer: the future of biology in biosensors.

    Science.gov (United States)

    Lim, Y C; Wiegmans, A P

    2016-04-01

    Circulating tumour cells associated with breast cancer (brCTCs) represent cells that have the capability to establish aggressive secondary metastatic tumours. The isolation and characterization of CTCs from blood in a single device is the future of oncology diagnosis and treatment. The methods of enrichment of CTCs have primarily utilized simple biological interactions with bimodal reporting with biased high purity and low numbers or low purity and high background. In this review, we will discuss the advances in microfluidics that has allowed the use of more complex selection criteria and biological methods to identify CTC populations. We will also discuss a potential new method of selection based on the response of the oncogenic DNA repair pathways within brCTCs. This method would allow insight into not only the oncogenic signalling at play but the chemoresistance mechanisms that could guide future therapeutic intervention at any stage of disease progression. PMID:26995223

  19. Urothelial Cancer Stem Cells

    Directory of Open Access Journals (Sweden)

    Irena Dimov

    2010-01-01

    Full Text Available There is mounting evidence supporting the idea that tumors, similar to normal adult tissues, arise from a specific stem-like cell population, the cancer stem cells (CSCs, which are considered as the real driving force behind tumor growth, the ability to metastasize, as well as resistance to conventional antitumor therapy. The concept that cancer growth recapitulates normal proliferative and/or regenerative processes, even though in very dysfunctional ways, has tremendous implications for cancer therapy. The rapid development of the CSC field, shoulder to shoulder with powerful genome-wide screening techniques, has provided cause for optimism for the development of more reliable therapies in the future. However, several important issues still lie ahead. Recent identification of a highly tumorigenic stem-like compartment and existence of urothelial differentiation programs in urothelial cell carcinomas (UCCs raised important questions about UCC initiation and development. This review examines the present knowledge on CSCs in UCCs regarding the similarities between CSCs and the adult urothelial stem cells, potential origin of urothelial CSCs, main regulatory pathways, surface markers expression, and the current state of CSC-targeting therapeutic strategies.

  20. Biological basis of heavy ion beams for cancer therapy

    International Nuclear Information System (INIS)

    Fast neutron therapy has started firstly and proton therapy has commenced secondly, fast neutron shows better biological effects compared to conventional radiations but its dose distribution is not good, and proton demonstrates excellent dose distribution but its biological effects are almost the same as that of conventional radiations. On the other hand, negative pi-mesons and heavy ions indicate high radiobiological effect and excellent dose distribution, therefore these particle radiations is considered to be more attractive for radiotherapeutic radiations to enhance cure rate of cancers. The biological strong points of these particles are as follows : 1) cells exposed to these particle radiations shows less recovery after irradiation compared to conventional radiations, 2) these radiations show high biological effects (high value of relative biological effectiveness = RBE) when the same dose is given, 3) big effects on hypoxic cells which exsist in tumor, i.e. the value of oxygen enhancement ratio (OER) is low, 4) the differences in radiosensitivity by stages of cell cycle are not so great (data was not shown in present paper), 5) biological effects at prepeak plateau region in depth dose curve formed by these particle radiations is less than that at peak region (therefore, if beam is modulated to cover tumor at spraed out broad peak, tumors is given more biological effect compared to normal tissues which is to be exposed to radiations at prepaeak region). Clinical trial using heavy ions are being performed at Lawrence Berkeley Laboratory which is only one facility to be able to try clinical trial. The results of clinical trials at Lawrence Berkeley Laboratory suggest to be very prospective to enhance tumor cure rate, however it is too early to estimate the effect of heavy ion therapy. (J.P.N.)

  1. Cancer Genomics and Biology 2015 – Meeting Report

    Science.gov (United States)

    Chow, Louis WC.; Costa, Luis; Teh, Bin-Tean; Li, Da-Qiang; Feng, Gu; Guan, Xin-Yuan; Nair, Asha; Zhu, Li; Sugimoto, Masahiro; Dutt, Amit; Toi, Masakazu; Gupta, Sudeep; Badwe, Rajendra; Knapp, Stefan; Pillai, M. Radhakrishna; Kumar, Rakesh

    2016-01-01

    The Cancer Genomics and Biology 2015 meeting embodied a three way collaboration among colleagues from the Global Cancer Genomics Consortium (GCGC), the Unifaith Cancer Institute China and Jiujiang University of China. The meeting marks the fifth and the last meeting of GCGC, which was formed in 2010. Previous four GCGC meetings have been held at the Tata Memorial Center- Mumbai, Institute of Molecular Medicine-Lisbon, and Graduate Medical School Kyoto University-Kyoto. In contrast to the genomic themes of the previous meetings, the 2015 conference theme was at the interface of laboratory and translation research and emerging therapeutics as reflected in the shared interests of all three collaborative entities – Cancer Genomics and Biology 2015. This year's conference was co-organized by the Jiujiang University at the Run Run Shaw building, Jiujiang University, Jiujiang City, China, on November 13 and 14, 2015. The conference attracted over 174 participants with 13 platform presentations. Scientific sessions included a plenary and five platform scientific sessions with themes ranging from biomarkers, stem cells and markers of the tumor microenvironment, proteomics and epigenetics, big data, to hormone and expression profiles. The meeting concluded with closing remarks by conference co-chairs emphasizing with the need to broaden membership across the globe, establishing priorities, and redrafting a white paper to launch a new consortium.

  2. A comparison of the biological effects of 125I seeds continuous low-dose-rate radiation and 60Co high-dose-rate gamma radiation on non-small cell lung cancer cells.

    Directory of Open Access Journals (Sweden)

    Zhongmin Wang

    Full Text Available To compare the biological effects of 125I seeds continuous low-dose-rate (CLDR radiation and 60Co γ-ray high-dose-rate (HDR radiation on non-small cell lung cancer (NSCLC cells.A549, H1299 and BEAS-2B cells were exposed to 125I seeds CLDR radiation or 60Co γ-ray HDR radiation. The survival fraction was determined using a colony-forming assay. The cell cycle progression and apoptosis were detected by flow cytometry (FCM. The expression of the apoptosis-related proteins caspase-3, cleaved-caspase-3, PARP, cleaved-PARP, BAX and Bcl-2 were detected by western blot assay.After irradiation with 125I seeds CLDR radiation, there was a lower survival fraction, more pronounced cell cycle arrest (G1 arrest and G2/M arrest in A549 and H1299 cells, respectively and a higher apoptotic ratio for A549 and H1299 cells than after 60Co γ-ray HDR radiation. Moreover, western blot assays revealed that 125I seeds CLDR radiation remarkably up-regulated the expression of Bax, cleaved-caspase-3 and cleaved-PARP proteins and down-regulated the expression of Bcl-2 proteins in A549 and H1299 cells compared with 60Co γ-ray HDR radiation. However, there was little change in the apoptotic ratio and expression of apoptosis-related proteins in normal BEAS-2B cells receiving the same treatment.125I seeds CLDR radiation led to remarkable growth inhibition of A549 and H1299 cells compared with 60Co HDR γ-ray radiation; A549 cells were the most sensitive to radiation, followed by H1299 cells. In contrast, normal BEAS-2B cells were relatively radio-resistant. The imbalance of the Bcl-2/Bax ratio and the activation of caspase-3 and PARP proteins might play a key role in the anti-proliferative effects induced by 125I seeds CLDR radiation, although other possibilities have not been excluded and will be investigated in future studies.

  3. Cell Science and Cell Biology Research at MSFC: Summary

    Science.gov (United States)

    2003-01-01

    The common theme of these research programs is that they investigate regulation of gene expression in cells, and ultimately gene expression is controlled by the macromolecular interactions between regulatory proteins and DNA. The NASA Critical Path Roadmap identifies Muscle Alterations and Atrophy and Radiation Effects as Very Serious Risks and Severe Risks, respectively, in long term space flights. The specific problem addressed by Dr. Young's research ("Skeletal Muscle Atrophy and Muscle Cell Signaling") is that skeletal muscle loss in space cannot be prevented by vigorous exercise. Aerobic skeletal muscles (i.e., red muscles) undergo the most extensive atrophy during long-term space flight. Of the many different potential avenues for preventing muscle atrophy, Dr. Young has chosen to study the beta-adrenergic receptor (betaAR) pathway. The reason for this choice is that a family of compounds called betaAR agonists will preferentially cause an increase in muscle mass of aerobic muscles (i.e., red muscle) in animals, potentially providing a specific pharmacological solution to muscle loss in microgravity. In addition, muscle atrophy is a widespread medical problem in neuromuscular diseases, spinal cord injury, lack of exercise, aging, and any disease requiring prolonged bedridden status. Skeletal muscle cells in cell culture are utilized as a model system to study this problem. Dr. Richmond's research ("Radiation & Cancer Biology of Mammary Cells in Culture") is directed toward developing a laboratory model for use in risk assessment of cancer caused by space radiation. This research is unique because a human model will be developed utilizing human mammary cells that are highly susceptible to tumor development. This approach is preferential over using animal cells because of problems in comparing radiation-induced cancers between humans and animals.

  4. Molecular biology-based diagnosis and therapy for pancreatic cancer

    International Nuclear Information System (INIS)

    Mainly described are author's investigations of the title subject through clinical and basic diagnosis/therapeutic approach. Based on their consideration of carcinogenesis and pathological features of pancreatic cancer (PC), analysis of expression of cancer-related genes in clinically available samples like pancreatic juice and cells biopsied can result in attaining their purposes. Desmoplasia, a pathological feature of PC, possibly induces resistance to therapy and one of strategies is probably its suppression. Targeting stem cells of the mesenchyma as well as those of PC is also a strategy in future. Authors' studies have revealed that quantitation of hTERT (coding teromerase) mRNA levels in PC cells micro-dissected from cytological specimens is an accurate molecular biological diagnostic method applicable clinically. Other cancer-related genes are also useful for the diagnosis and mucin (MUC) family genes are shown to be typical ones for differentiating the precancerous PC, PC and chronic pancreatisis. Efficacy of standard gemcitabine chemotherapy can be individualized with molecular markers concerned to metabolism of the drug like dCK. Radiotherapy/radio-chemotherapy are not so satisfactory for PC treatment now. Authors have found elevated MMP-2 expression and HGF/c-Met signal activation in irradiated PC cells, which can increase the invasive capability; and stimulation of phosphorylation and activation of c-Met/MARK in co-culture of irradiated PC cells with messenchymal cells from PC, which possibly leads to progression of malignancy of PC through their interaction, of which suppression, therefore, can be a new approach to increase the efficacy of radiotherapy. Authors are making effort to introducing adenovirus therapy in clinic; exempli gratia (e.g.), the virus carrying wild type p53, a cancer-suppressive gene, induces apoptosis of PC cells often having its mutated gene. (T.T.)

  5. Cancer stem cells in head and neck cancer

    Directory of Open Access Journals (Sweden)

    Trapasso S

    2012-11-01

    the presence of specific surface markers for selective cytotoxic agent vehicles. Finally, some research groups are trying to induce these cells to differentiate, thus making them easier to remove. For all these reasons, we have collected existing literature on head and neck cancer stem cells that correlate the biological characteristics of this subpopulation of cancer cells with the clinical behavior of tumors.Keywords: head and neck cancer, cancer stem cells, tumor markers

  6. Clinical Outcomes of Biological Effective Dose-Based Fractionated Stereotactic Radiation Therapy for Metastatic Brain Tumors From Non-Small Cell Lung Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Matsuyama, Tomohiko, E-mail: matsutomo_llp@yahoo.co.jp [Department of Radiation Oncology, Kumamoto University, Kumamoto (Japan); Kogo, Kasei [Kumamoto Radiosurgery Clinic, Kumamoto (Japan); Oya, Natsuo [Department of Radiation Oncology, Kumamoto University, Kumamoto (Japan)

    2013-03-15

    Purpose: To evaluate the efficacy and toxicity of fractionated stereotactic radiation therapy (FSRT) based on biological effective dose (BED), a novel approach to deliver a fixed BED irrespective of dose fractionation, for brain metastases from non-small cell lung cancer (NSCLC). Methods and Materials: Between March 2005 and March 2009 we treated 299 patients with 1 to 5 lesions from NSCLC (573 total brain metastases) with FSRT using Novalis. The dose fractionation schedules were individually determined to deliver a peripheral BED10 (α/β ratio = 10) of approximately 80 Gy{sub 10}. The median number of fractions was 3 (range, 2-10), the median peripheral BED10 was 83.2 Gy (range, 19.1-89.6 Gy). Patients were followed up with magnetic resonance imaging (MRI) studies performed at 1- to 2-month intervals. The local tumor control rate and overall local progression-free and intracranial relapse-free survival were calculated by the Kaplan-Meier method. Results: Local control rates for all 573 lesions at 6 and 12 months were 96.3% and 94.5%, respectively. By multivariate analysis the tumor diameter was the only factor predictive of the local control rate (P=.001). The median overall survival, local progression-free survival, and intracranial relapse-free survival were 17.1, 14.9, and 4.4 months, respectively. The overall survival, local progression-free survival, and intracranial relapse-free survival rates at 6 and 12 months were 78.5% and 63.3%, 74.3% and 57.8%, and 41.0% and 21.8%, respectively. Six patients (2%) manifested progressive radiation injury to the brain even during therapy with corticosteroids; they underwent hyperbaric oxygen therapy, and follow-up MRI showed improvement. Conclusions: This study showed that BED-based FSRT for brain metastases from NSCLC is a promising strategy that may yield excellent outcomes with acceptable toxicity. Criteria must be established to determine the optimal dose fractionation for individual patients.

  7. Increased Biological Effective Dose of Radiation Correlates with Prolonged Survival of Patients with Limited-Stage Small Cell Lung Cancer: A Systematic Review.

    Directory of Open Access Journals (Sweden)

    Lucheng Zhu

    Full Text Available Thoracic radiotherapy (TRT is a critical component of the treatment of limited-stage small cell lung cancer (LS-SCLC. However, the optimal radiation dose/fractionation remains elusive. This study reviewed current evidence and explored the dose-response relationship in patients with LS-SCLC who were treated with radiochemotherapy.A quantitative analysis was performed through a systematic search of PubMed, Web of Science, and the Cochrane Library. The correlations between the biological effective dose (BED and median overall survival (mOS, median progression-free survival (mPFS, 1-, 3-, and 5-year overall survival (OS as well as local relapse (LR were evaluated.In all, 2389 patients in 19 trials were included in this study. Among these 19 trials, seven were conducted in Europe, eight were conducted in Asia and four were conducted in the United States. The 19 trials that were included consisted of 29 arms with 24 concurrent and 5 sequential TRT arms. For all included studies, the results showed that a higher BED prolonged the mOS (R2 = 0.198, p<0.001 and the mPFS (R2 = 0.045, p<0.001. The results also showed that increased BED improved the 1-, 3-, and 5-year OS. A 10-Gy increment added a 6.3%, a 5.1% and a 3.7% benefit for the 1-, 3-, and 5-year OS, respectively. Additionally, BED was negatively correlated with LR (R2 = 0.09, p<0.001. A subgroup analysis of concurrent TRT showed that a high BED prolonged the mOS (p<0.001 and the mPFS (p<0.001, improved the 1-, 3-, and 5-year OS (p<0.001 and decreased the rate of LR (p<0.001.This study showed that an increased BED was associated with improved OS, PFS and decreased LR in patients with LS-SCLC who were treated with combined chemoradiotherapy, which indicates that the strategy of radiation dose escalation over a limited time frame is worth exploring in a prospective clinical trial.

  8. Clinical Outcomes of Biological Effective Dose-Based Fractionated Stereotactic Radiation Therapy for Metastatic Brain Tumors From Non-Small Cell Lung Cancer

    International Nuclear Information System (INIS)

    Purpose: To evaluate the efficacy and toxicity of fractionated stereotactic radiation therapy (FSRT) based on biological effective dose (BED), a novel approach to deliver a fixed BED irrespective of dose fractionation, for brain metastases from non-small cell lung cancer (NSCLC). Methods and Materials: Between March 2005 and March 2009 we treated 299 patients with 1 to 5 lesions from NSCLC (573 total brain metastases) with FSRT using Novalis. The dose fractionation schedules were individually determined to deliver a peripheral BED10 (α/β ratio = 10) of approximately 80 Gy10. The median number of fractions was 3 (range, 2-10), the median peripheral BED10 was 83.2 Gy (range, 19.1-89.6 Gy). Patients were followed up with magnetic resonance imaging (MRI) studies performed at 1- to 2-month intervals. The local tumor control rate and overall local progression-free and intracranial relapse-free survival were calculated by the Kaplan-Meier method. Results: Local control rates for all 573 lesions at 6 and 12 months were 96.3% and 94.5%, respectively. By multivariate analysis the tumor diameter was the only factor predictive of the local control rate (P=.001). The median overall survival, local progression-free survival, and intracranial relapse-free survival were 17.1, 14.9, and 4.4 months, respectively. The overall survival, local progression-free survival, and intracranial relapse-free survival rates at 6 and 12 months were 78.5% and 63.3%, 74.3% and 57.8%, and 41.0% and 21.8%, respectively. Six patients (2%) manifested progressive radiation injury to the brain even during therapy with corticosteroids; they underwent hyperbaric oxygen therapy, and follow-up MRI showed improvement. Conclusions: This study showed that BED-based FSRT for brain metastases from NSCLC is a promising strategy that may yield excellent outcomes with acceptable toxicity. Criteria must be established to determine the optimal dose fractionation for individual patients

  9. DNA From Dead Cancer Cells Induces TLR9-Mediated Invasion and Inflammation In Living Cancer Cells

    Science.gov (United States)

    Tuomela, Johanna; Sandholm, Jouko; Kaakinen, Mika; Patel, Ankita; Kauppila, Joonas H.; Ilvesaro, Joanna; Chen, Dongquan; Harris, Kevin W.; Graves, David; Selander, Katri S.

    2014-01-01

    TLR9 is a cellular DNA-receptor, which is widely expressed in breast and other cancers. Although synthetic TLR9-ligands induce cancer cell invasion in vitro, the role of TLR9 in cancer pathophysiology has remained unclear. We show here that living cancer cells uptake DNA from chemotherapy-killed cancer cells. We discovered that such DNA induces TLR9- and cathepsin-mediated invasion in living cancer cells. To study whether this phenomenon contributes to treatment responses, triple negative, human MDA-MB-231 breast cancer cells stably expressing control or TLR9 siRNA were inoculated orthotopically into nude mice. The mice were treated with vehicle or doxorubicin. The tumor groups exhibited equal decreases in size in response to doxorubicin. However, while the weights of vehicle-treated mice were similar, mice bearing control siRNA tumors became significantly more cachectic in response to doxorubicin, as compared with similarly treated mice bearing TLR9 siRNA tumors, suggesting a TLR9-mediated inflammation at the site of the tumor. In conclusion, our findings propose that DNA released from chemotherapy-killed cancer cells has significant influence on TLR9-mediated biological effects in living cancer cells. Through these mechanisms, tumor TLR9 expression may affect treatment responses to chemotherapy. PMID:24212717

  10. Biological behaviors of lung cancer stem-like cells from human large-cell lung cancer cell line H460%大细胞肺癌H460细胞系肿瘤干细胞样细胞生物学特性

    Institute of Scientific and Technical Information of China (English)

    刘攀; 周向东

    2014-01-01

    目的利用无血清条件悬浮培养人大细胞肺癌H460系,从中分离到肺癌干细胞并进行其生物学特性研究。方法无血清条件培养法悬浮培养H460细胞形成悬浮细胞球,通过qPCR、Western blot、流式细胞术、平皿克隆形成等实验,比较H460细胞和H460细胞球中干性相关分子表达水平及细胞增殖能力强弱,并利用裸鼠移植瘤形成实验研究肺癌细胞干细胞球的体内生物学特性。结果利用无血清条件培养法成功从H460细胞中分离出悬浮生长的肿瘤干细胞样细胞,其增殖能力强于H460贴壁细胞(P<0.05),干细胞相关转录因子Sox2、Oct4和Nanog表达在mRNA及蛋白水平均有增加(尤以Nanog提升水平明显(P<0.01)),细胞球在裸鼠体内具有较强成瘤能力。结论无血清条件培养法可以有效富集到H460细胞系中的肺癌干细胞,Nanog可能与H460细胞系中CSLCs的干性特征维持相关。%Objective To isolate lung cancer stem-like cells (LCSCs) from human large-cell lung cancer cell line NCI-H460 (H460) and explore their biological characteristics. Methods H460 cells were cultured in serum-free medium in the presence of specific growth factors. Quantitative PCR (qPCR), flow cytometry and colony formation assay were performed to characterize the stemness of H460 spheres. Adherent H460 cells and H460 cell spheres were inoculated subcutaneously in nude mice and the tumor growth was assessed. Results The isolated LCSCs from H460 cells in serum-free medium grew as floating cell spheres and exhibited stronger proliferative activity than H460 cells. Compared with H460 cells, H460 cells spheres showed higher expressions of stem cell markers Sox2, Oct4, and especially Nanog, and possessed a stronger tumorgenicity in nude mice. Conclusion The serum-free culture system can effectively enrich lung cancer stem cells from human lung cancer stem cell line H460, and the high expression of Nanog may

  11. Biologic effect of neurogenesis in pancreatic cancer.

    Science.gov (United States)

    He, Dandan; Manzoni, Adriana; Florentin, Diego; Fisher, William; Ding, Yi; Lee, MinJae; Ayala, Gustavo

    2016-06-01

    Pancreatic cancer (PaCA) is a deadly disease with few systemic therapeutic options. The head of the pancreas is the most innervated part and most common location of cancer. However, little is known about the contribution of the nerve-cancer interaction to facilitate pancreatic progression. To quantify PaCA axonogenesis, we used a 3-dimensional in vitro neurogenesis model. In addition, neurogenesis in human PaCA was analyzed using PGP9.5 immunohistochemistry, deconvolution imaging, and image segmentation and analysis. There was a significant increase of the total area of neurites in the in vitro coculture with dorsal root ganglia group than control. The nerve density in PaCA tissue was significantly higher than normal pancreatic tissue. To study the functional role of nerves in PaCA, male athymic nude (Nu-Nu) mice were divided into 3 groups: (A) animals were coinjected with MIA PaCa-2 cells and 20U/kg weight units of Botulinum toxin (Botox) (n=10); (B) first injected with Botox and 6weeks later MIA PaCa-2 cancer cells (n=4); and (C) control animals were injected with equivalent amounts of saline fluid (n=9). Animals were sacrificed 6weeks later. Tumor size and apoptotic count (terminal deoxynucleotidyl transferase dUTP nick-end labeling) were measured. Tumor size was decreased and apoptotic rate increased in Botox-treated PaCA. Our data indicate that neural microenvironment may play an important role in the progression of PaCA. It may lead to novel nerve-targeted coadjuvant therapies for PaCA. PMID:26980040

  12. Evolutionary cell biology: two origins, one objective.

    Science.gov (United States)

    Lynch, Michael; Field, Mark C; Goodson, Holly V; Malik, Harmit S; Pereira-Leal, José B; Roos, David S; Turkewitz, Aaron P; Sazer, Shelley

    2014-12-01

    All aspects of biological diversification ultimately trace to evolutionary modifications at the cellular level. This central role of cells frames the basic questions as to how cells work and how cells come to be the way they are. Although these two lines of inquiry lie respectively within the traditional provenance of cell biology and evolutionary biology, a comprehensive synthesis of evolutionary and cell-biological thinking is lacking. We define evolutionary cell biology as the fusion of these two eponymous fields with the theoretical and quantitative branches of biochemistry, biophysics, and population genetics. The key goals are to develop a mechanistic understanding of general evolutionary processes, while specifically infusing cell biology with an evolutionary perspective. The full development of this interdisciplinary field has the potential to solve numerous problems in diverse areas of biology, including the degree to which selection, effectively neutral processes, historical contingencies, and/or constraints at the chemical and biophysical levels dictate patterns of variation for intracellular features. These problems can now be examined at both the within- and among-species levels, with single-cell methodologies even allowing quantification of variation within genotypes. Some results from this emerging field have already had a substantial impact on cell biology, and future findings will significantly influence applications in agriculture, medicine, environmental science, and synthetic biology. PMID:25404324

  13. [Molecular biological predictors for kidney cancer].

    Science.gov (United States)

    Vtorushin, S V; Tarakanova, V O; Zavyalova, M V

    2016-01-01

    The paper considers the data available in the modern literature on studies of potential molecular predictors for renal cell carcinoma (RCC). Investigations of cell death markers, namely; Bcl-2 as an inhibitor of apoptosis, are of interest. Its high expression correlates with a more favorable prognosis. Inactivation of Berclin 1 that is an authophagy indicator in intact tissues gives rise to t high risk for tumorigenesis. At the same time, high Beclin 1 expression in the tissue of the tumor itself results in the lower efficiency of performed chemotherapy. Excess annexin A2 in the tumor promotes the growth and invasion of cancer cells. Patients with tumor over-expression of SAM68 protein involved in cell proliferation have a lower overall survival rate. The lifespan of patients without distinct metastases survive significantly longer in the overexpression of epithelial cell adhesion molecule (EpCAM). High PD-L1 protein expression on the cell membrane is considered to be a potential marker of effective immunotherapy for RCC. PMID:27077146

  14. Phenotype heterogeneity in cancer cell populations

    Science.gov (United States)

    Almeida, Luis; Chisholm, Rebecca; Clairambault, Jean; Escargueil, Alexandre; Lorenzi, Tommaso; Lorz, Alexander; Trélat, Emmanuel

    2016-06-01

    Phenotype heterogeneity in cancer cell populations, be it of genetic, epigenetic or stochastic origin, has been identified as a main source of resistance to drug treatments and a major source of therapeutic failures in cancers. The molecular mechanisms of drug resistance are partly understood at the single cell level (e.g., overexpression of ABC transporters or of detoxication enzymes), but poorly predictable in tumours, where they are hypothesised to rely on heterogeneity at the cell population scale, which is thus the right level to describe cancer growth and optimise its control by therapeutic strategies in the clinic. We review a few results from the biological literature on the subject, and from mathematical models that have been published to predict and control evolution towards drug resistance in cancer cell populations. We propose, based on the latter, optimisation strategies of combined treatments to limit emergence of drug resistance to cytotoxic drugs in cancer cell populations, in the monoclonal situation, which limited as it is still retains consistent features of cell population heterogeneity. The polyclonal situation, that may be understood as "bet hedging" of the tumour, thus protecting itself from different sources of drug insults, may lie beyond such strategies and will need further developments. In the monoclonal situation, we have designed an optimised therapeutic strategy relying on a scheduled combination of cytotoxic and cytostatic treatments that can be adapted to different situations of cancer treatments. Finally, we review arguments for biological theoretical frameworks proposed at different time and development scales, the so-called atavistic model (diachronic view relying on Darwinian genotype selection in the coursof billions of years) and the Waddington-like epigenetic landscape endowed with evolutionary quasi-potential (synchronic view relying on Lamarckian phenotype instruction of a given genome by reversible mechanisms), to

  15. Bioimpedance spectroscopy of breast cancer cells: A microsystems approach

    OpenAIRE

    Srinivasaraghavan, Vaishnavi

    2015-01-01

    Bioimpedance presents a versatile, label-free means of monitoring biological cells and their responses to physical, chemical and biological stimuli. Breast cancer is the second most common type of cancer among women in the United States. Although significant progress has been made in diagnosis and treatment of this disease, there is a need for robust, easy-to-use technologies that can be used for the identification and discrimination of critical subtypes of breast cancer in biopsies obtained ...

  16. The biology of circulating tumor cells.

    Science.gov (United States)

    Pantel, K; Speicher, M R

    2016-03-10

    Metastasis is a biologically complex process consisting of numerous stochastic events which may tremendously differ across various cancer types. Circulating tumor cells (CTCs) are cells that are shed from primary tumors and metastatic deposits into the blood stream. CTCs bear a tremendous potential to improve our understanding of steps involved in the metastatic cascade, starting from intravasation of tumor cells into the circulation until the formation of clinically detectable metastasis. These efforts were propelled by novel high-resolution approaches to dissect the genomes and transcriptomes of CTCs. Furthermore, capturing of viable CTCs has paved the way for innovative culturing technologies to study fundamental characteristics of CTCs such as invasiveness, their kinetics and responses to selection barriers, such as given therapies. Hence the study of CTCs is not only instrumental as a basic research tool, but also allows the serial monitoring of tumor genotypes and may therefore provide predictive and prognostic biomarkers for clinicians. Here, we review how CTCs have contributed to significant insights into the metastatic process and how they may be utilized in clinical practice. PMID:26050619

  17. A new prospect in cancer therapy: targeting cancer stem cells to eradicate cancer

    OpenAIRE

    Yi-Min Zhu; Li-Hua Yuan; Ke-Feng Pu; Bing Dong; An-Xin Wang; Li-Sha Chen

    2012-01-01

    According to the cancer stem cell theory, cancers can be initiated by cancer stem cells. This makes cancer stem cells prime targets for therapeutic intervention. Eradicating cancer stem cells by efficient targeting agents may have the potential to cure cancer. In this review, we summarize recent breakthroughs that have improved our understanding of cancer stem cells, and we discuss the therapeutic strategy of targeting cancer stem cells, a promising future direction for cancer stem cell resea...

  18. A new prospect in cancer therapy: targeting cancer stem cells to eradicate cancer

    Institute of Scientific and Technical Information of China (English)

    Li-Sha Chen; An-Xin Wang; Bing Dong; Ke-Feng Pu; Li-Hua Yuan; Yi-Min Zhu

    2012-01-01

    According to the cancer stem cell theory,cancers can be initiated by cancer stem cells.This makes cancer stem cells prime targets for therapeutic intervention.Eradicating cancer stem cells by efficient targeting agents may have the potential to cure cancer.In this review,we summarize recent breakthroughs that have improved our understanding of cancer stem cells,and we discuss the therapeutic strategy of targeting cancer stem cells,a promising future direction for cancer stem cell research.

  19. Microfluidic tools for cell biological research

    OpenAIRE

    Velve-Casquillas, Guilhem; Le Berre, Maël; Piel, Matthieu; Tran, Phong T.

    2010-01-01

    Microfluidic technology is creating powerful tools for cell biologists to control the complete cellular microenvironment, leading to new questions and new discoveries. We review here the basic concepts and methodologies in designing microfluidic devices, and their diverse cell biological applications.

  20. Advanced research on separating prostate cancer stem cells

    International Nuclear Information System (INIS)

    Prostate cancer is a common malignant tumor in male urinary system,and may easily develop into the hormone refractory prostate cancer which can hardly be cured. Recent studies had found that the prostate cancer stem cells may be the source of the prostate cancer's occurrence,development, metastasis and recurrence. The therapy targeting the prostate cancer stem cells may be the effective way to cure prostate cancer. But these cells is too low to be detected. The difficulty lies in the low separation efficiency of prostate cancer stem cell, so the effectively separating prostate cancer stem cells occupied the main position for the more in-depth research of prostate cancer stem cells. This paper reviews the research progress and existing problems on the several main separating methods of prostate cancer stem cells, includes the fluorescence activated cells sorting and magnetic activated cells sorting based on prostate cancer stem cell surface markers, the side-population sorting and serum-free medium sphere forming sorting based on prostate cancer stem cell's biology. (authors)

  1. Immunotargeting of cancer stem cells

    OpenAIRE

    Kwiatkowska-Borowczyk, Eliza P.; Gąbka-Buszek, Agnieszka; Jankowski, Jakub; Mackiewicz, Andrzej

    2015-01-01

    Cancer stem cells (CSCs) represent a distinctive population of tumour cells that control tumour initiation, progression, and maintenance. Their influence is great enough to risk the statement that successful therapeutic strategy must target CSCs in order to eradicate the disease. Because cancer stem cells are highly resistant to chemo- and radiotherapy, new tools to fight against cancer have to be developed. Expression of antigens such as ALDH, CD44, EpCAM, or CD133, which distinguish CSCs fr...

  2. Systems biology in the frontier of cancer research: a report of the Second International Workshop of Cancer Systems Biology

    OpenAIRE

    Ying Xu; Yan-Chun Liang; Juan Cui

    2012-01-01

    The report summarizes the Second International Workshop of Cancer Systems Biology held on July 5-6, 2012 in Changchun, China. The goal of the workshop was to bring together cancer researchers with different backgrounds to share their views about cancer and their experiences in fighting against cancer, and to gain new and systems-level understanding about cancer formation, progression, diagnosis, and treatment through exchanging ideas.

  3. Systems biology in the frontier of cancer research:a report of the Second International Workshop of Cancer Systems Biology

    Institute of Scientific and Technical Information of China (English)

    Juan Cui; Yan-Chun Liang; Ying Xu

    2012-01-01

    The report summarizes the Second International Workshop of Cancer Systems Biology held on July 5-6,2012 in Changchun,China.The goal of the workshop was to bring together cancer researchers with different backgrounds to share their views about cancer and their experiences in fighting against cancer,and to gain new and systems-level understanding about cancer formation,progression,diagnosis,and treatment through exchanging ideas.

  4. Biological profile of {sup 99m}Tc-HYNIC-betaAla-NT(8-13) in MDAMB-231 breast cancer cell line

    Energy Technology Data Exchange (ETDEWEB)

    Teodoro, Rodrigo; Faintuch, Bluma L.; Wiecek, Danielle P.; Silva, Natanael G.; Vallejo, Natalia M., E-mail: teodoro_rodrigo@yahoo.com.b [Instituto de Pesquisas Energeticas e Nucleares (IPEN/CNEN-SP), Sao Paulo, SP (Brazil). Diretoria de Radiofarmacia

    2009-07-01

    Introduction: Neurotensin (NT) is a tridecapeptide involved in several growth-steps of human cancers. Recent studies postulated the role of NT and NT-receptor subtype 1 in breast cancer progression. However, the main drawback of natural NT is its rapid degradation in plasma. In an effort to develop a NT peptide-based radiopharmaceutical for the detection of breast cancer, the aim of this study was the radiolabeling of the double stabilized NT(8-13) peptide using HYNIC as chelating agent. Methods: Conjugated HYNIC-betaAla-NT(8-13) was labeled with {sup 99m}Tc using tricine and EDDA as coligands. Radiochemical purity was checked by TLC and confirmed by RP-HPLC. {sup 99m}Tc-HYNIC-betaAla-NT(8-13) (0.1 mL/74 MBq) was administered in Nude mice bearing MDA-MB-231 breast cancer cells and biodistribution studies were carried out at 30 and 90 min postinjection (pi). Blocking evaluation was also conducted by co-injection of 115 nmol of cold NT (8-13) analog. Planar gamma-camera imaging was acquired at the earlier time point studied. Results: Radiochemical purity of the radioconjugate was higher than 99%. Biodistribution studies revealed a very fast accumulation in tumor (1.97+-0.18% ID/g, 30 min pi) with a sharply decrease at the later time point studied (0.44+-0.02% ID/g). The specificity of the radioconjugate was evaluated with blockade studies. A reduction of 45.94%, 27.73% and 36.39% was found for tumor, large and small intestines, respectively, at 30 min pi. Otherwise, a less impressive blockade was observed for tumor and small intestine (28.68% and 24.90%, respectively) at the later time point studied. Conclusion: The results provide encouraging evidence in the development of radiolabeled NT(8-13) analogues for breast cancer diagnosis. (author)

  5. Biological profile of 99mTc-HYNIC-βAla-NT(8-13) in MDAMB-231 breast cancer cell line

    International Nuclear Information System (INIS)

    Introduction: Neurotensin (NT) is a tridecapeptide involved in several growth-steps of human cancers. Recent studies postulated the role of NT and NT-receptor subtype 1 in breast cancer progression. However, the main drawback of natural NT is its rapid degradation in plasma. In an effort to develop a NT peptide-based radiopharmaceutical for the detection of breast cancer, the aim of this study was the radiolabeling of the double stabilized NT(8-13) peptide using HYNIC as chelating agent. Methods: Conjugated HYNIC-βAla-NT(8-13) was labeled with 99mTc using tricine and EDDA as coligands. Radiochemical purity was checked by TLC and confirmed by RP-HPLC. 99mTc-HYNIC-βAla-NT(8-13) (0.1 mL/74 MBq) was administered in Nude mice bearing MDA-MB-231 breast cancer cells and biodistribution studies were carried out at 30 and 90 min postinjection (pi). Blocking evaluation was also conducted by co-injection of 115 nmol of cold NT (8-13) analog. Planar gamma-camera imaging was acquired at the earlier time point studied. Results: Radiochemical purity of the radioconjugate was higher than 99%. Biodistribution studies revealed a very fast accumulation in tumor (1.97±0.18% ID/g, 30 min pi) with a sharply decrease at the later time point studied (0.44±0.02% ID/g). The specificity of the radioconjugate was evaluated with blockade studies. A reduction of 45.94%, 27.73% and 36.39% was found for tumor, large and small intestines, respectively, at 30 min pi. Otherwise, a less impressive blockade was observed for tumor and small intestine (28.68% and 24.90%, respectively) at the later time point studied. Conclusion: The results provide encouraging evidence in the development of radiolabeled NT(8-13) analogues for breast cancer diagnosis. (author)

  6. Molecular biology and riddle of cancer: the ‘Tom & Jerry’ show

    Directory of Open Access Journals (Sweden)

    Md. Al Mamun

    2011-11-01

    Full Text Available From the conventional Bird’s eye, cancer initiation and metastasis are generally intended to be understood beneath the light of classical clonal genetic, epigenetic and cancer stem cell model. But inspite decades of investigation, molecular biology has shown hard success to give Eagle’s eye in unraveling the riddle of cancer. And it seems, tiring Tom runs in vague behind naughty Jerry.

  7. Prostate stem cells and cancer

    OpenAIRE

    Nikitin, Alexander Y.; Matoso, A; Roy-Burman, P

    2007-01-01

    Properties shared by neoplastic and stem cells indicate a possibility that somatic stem cells or transit-amplifying cells that have reacquired stem cell properties, particularly the ability for self-renewal, represent favorable targets for malignant transformation. In this review we discuss significance of the stem cell model for understanding prostate cancer pathogenesis and describe relevant studies in animals. It is proposed that dissemination of rare cancer stem ce...

  8. General Information about Small Cell Lung Cancer

    Science.gov (United States)

    ... Cancer Prevention Lung Cancer Screening Research Small Cell Lung Cancer Treatment (PDQ®)–Patient Version General Information About Small Cell Lung Cancer Go to Health Professional Version Key Points Small ...

  9. Stages of Small Cell Lung Cancer

    Science.gov (United States)

    ... Cancer Prevention Lung Cancer Screening Research Small Cell Lung Cancer Treatment (PDQ®)–Patient Version General Information About Small Cell Lung Cancer Go to Health Professional Version Key Points Small ...

  10. Treatment Option Overview (Small Cell Lung Cancer)

    Science.gov (United States)

    ... Cancer Prevention Lung Cancer Screening Research Small Cell Lung Cancer Treatment (PDQ®)–Patient Version General Information About Small Cell Lung Cancer Go to Health Professional Version Key Points Small ...

  11. Cancer stem cells in head and neck cancer.

    Science.gov (United States)

    Allegra, Eugenia; Trapasso, Serena

    2012-01-01

    differentiate, thus making them easier to remove. For all these reasons, we have collected existing literature on head and neck cancer stem cells that correlate the biological characteristics of this subpopulation of cancer cells with the clinical behavior of tumors. PMID:23189032

  12. Noncoding RNAs in cancer and cancer stem cells

    Institute of Scientific and Technical Information of China (English)

    Tianzhi Huang; Angel Alvarez; Bo Hu; Shi-Yuan Cheng

    2013-01-01

    In recent years, it has become increasingly apparent that noncoding RNAs (ncRNA) are of crucial importance for human cancer. The functional relevance of ncRNAs is particularly evident for microRNAs (miRNAs) and long noncoding RNAs (lncRNAs). miRNAs are endogenously expressed small RNA sequences that act as post-transcriptional regulators of gene expression and have been extensively studied for their roles in cancers, whereas lncRNAs are emerging as important players in the cancer paradigm in recent years. These noncoding genes are often aberrantly expressed in a variety of human cancers. However, the biological functions of most ncRNAs remain largely unknown. Recently, evidence has begun to accumulate describing how ncRNAs are dysregulated in cancer and cancer stem cells, a subset of cancer cells harboring self-renewal and differentiation capacities. These studies provide insight into the functional roles that ncRNAs play in tumor initiation, progression, and resistance to therapies, and they suggest ncRNAs as attractive therapeutic targets and potential y useful diagnostic tools.

  13. Metastatic renal cell cancer treatments.

    Science.gov (United States)

    Sternberg, C N

    2003-01-01

    Metastatic renal cell carcinoma has been considered to be resistant to chemotherapy, with responses observed in only limited numbers of patients. For this reason, therapeutic options have ranged from no treatment, to immunotherapy with cytokines such as IL-2 and interferon-alpha, chemotherapy alone or in combination with cytokines, and to a variety of new investigational approaches. Interferon and interleukin-2 (IL-2) have led to long-term survival in selected patients. Immunotherapy with cytokines, monoclonal antibodies, new agents, dendritic cell therapy, and allotransplantation offer promise. Novel therapeutic strategies include combining cytokines, and antiangiogenic approaches such as thalidomide and antivascular endothelial growth factor therapy. Pathologic, cytogenic and molecular studies have proven that renal cell carcinoma is not a single tumor entity. Efforts to improve results also include the identification of prognostic factors, which allow treatment to be better directed towards those patients most likely to benefit. Increasing understanding of cancer biology is beginning to allow for a more targeted approach to the therapy of metastatic renal cell carcinoma. Adequate positioning of known treatments is essential and many trials of new targeted therapies are underway. PMID:14988745

  14. Ovarian cancer: emerging concept on cancer stem cells

    OpenAIRE

    Ponnusamy Moorthy P; Batra Surinder K

    2008-01-01

    Abstract Emerging evidence suggests that the capacity of a tumor to grow and propagate is dependent on a small subset of cells within a tumor, termed cancer stem cells. In fact, cancer cells, like stem cells, can proliferate indefinitely through a dysregulated cellular self-renewal capacity. Cancer stem cells may originate due to the distribution into self-renewal and differentiation pathways occurring in multi-potential stem cells, tissue-specific stem cells, progenitor cells and cancer cell...

  15. Molecular Biology of Pancreatic Cancer: How Useful Is It in Clinical Practice?

    Directory of Open Access Journals (Sweden)

    George H Sakorafas

    2012-07-01

    Full Text Available Context During the recent two decades dramatic advances of molecular biology allowed an in-depth understanding of pancreatic carcinogenesis. It is currently accepted that pancreatic cancer has a genetic component. The real challenge is now how these impressive advances could be used in clinical practice. Objective To critically present currently available data regarding clinical application of molecular biology in pancreatic cancer. Methods Reports about clinical implications of molecular biology in patients with pancreatic cancer were retrieved from PubMed. These reports were selected on the basis of their clinical relevance, and the data of their publication (preferentially within the last 5 years. Emphasis was placed on reports investigating diagnostic, prognostic, and therapeutic implications. Results Molecular biology can be used to identify individuals at high-risk for pancreatic cancer development. Intensive surveillance is indicated in these patients to detect pancreatic neoplasia ideally at a preinvasive stage, when curative resection is still possible. Molecular biology can also be used in the diagnosis of pancreatic cancer, with molecular analysis on samples of biologic material, such as serum or plasma, duodenal fluid or preferentially pure pancreatic juice, pancreatic cells or tissue, and stools. Molecular indices have also prognostic significance. Finally, molecular biology may have therapeutic implications by using various therapeutic approaches, such as antiangiogenic factors, purine synthesis inhibitors, matrix metalloproteinase inhibitors, factors modulating tumor-stroma interaction, inactivation of the hedgehog pathway, gene therapy, oncolytic viral therapy, immunotherapy (both passive as well as active etc. Conclusion Molecular biology may have important clinical implications in patients with pancreatic cancer and represents one of the most active areas on cancer research. Hopefully clinical applications of molecular biology

  16. Radiation sensitizations at DNA-level by chemical and biological agents. Coordinated programme on improvement of radiotherapy of cancer using modifiers of radiosensitivity of cells

    International Nuclear Information System (INIS)

    Radiation sensitization by chemical agents at DNA level is discussed. Procaine, Halothan and Metronidazole showed no significant effect on unscheduled DNA synthesis (UDS) in mouse spleen cells, investigated by autoradiography and no effect on rejoining of DNA single strand breaks after gamma or UV irradiation. Oxyphenbutazon and prednisolone reduced the replicative DNA synthesis in vitro and in vivo but there was only little effect on DNA repair in the in vivo experiments. These two substances showed also a small reduction in poly(ADP-ribose) synthesis (PAR synthesis). 5-methoxypsoralen (5-MOP) and 8-methoxypsoralen (8-MOP) in combination with UV irradiation showed that 5-MOP was more toxic than mutagen, but induced much less DNA crosslinks than 8-MOP. Autoradiographic studies of radiation sensitization by biological agents showed significant inhibition of UDS in Yoshida tumor cells after acute mycoplasma infection in rats. Nucleoid sedimentation studies showed only in the case of Yoshida tumor cells after mycoplasma infection a dramatic effect in the sedimentation behaviour. Sensitization of cells by changing chromatin structure was also studied. Benzamide, 3-NH2-benzamide, 3-Methoxybenzamide, Spermine, Theophyllin and Caffeine were tested in different concentrations on replicative DNA synthesis, UDS after UV irradiation and PAR synthesis Chinese hamster ovary cells. 5-Methoxybenzamide was the strongest sensitizer and inhibitor of the PAR synthesis, and was used in further experiments. Results of KFA Juelich on sensitization of a mamma-adenocarcinoma EO 771 on C57 B1 mice are given. Replicative DNA synthesis, DNA repair and PAR synthesis were compared in spleen cells and adenocarcinoma cells after treatment with 5-Methoxybenzamide. An inhibitory effect on UDS could be shown only in adenocarcinoma cells but not in the mice spleen cells

  17. The new stem cell biology.

    OpenAIRE

    Quesenberry, Peter J.; Colvin, Gerald A; Lambert, Jean-Francois; Frimberger, Angela E.; Dooner, Mark S.; Mcauliffe, Christina I.; Miller, Caroline; Becker, Pamela; Badiavas, Evangelis; Falanga, Vincent J.; Elfenbein, Gerald; Lum, Lawrence G.

    2002-01-01

    Recent studies have indicated that bone marrow stem cells are capable of generating muscle, cardiac, hepatic, renal, and bone cells. Purified hematopoietic stem cells have generated cardiac and hepatic cells and reversed disease manifestations in these tissues. Hematopoietic stem cells also alter phenotype with cell cycle transit or circadian phase. During a cytokine stimulated cell cycle transit, reversible alterations of differentiation and engraftment occur. Primitive hematopoietic stem ce...

  18. Synthesis and Biological Activity of Diastereomeric and Geometric Analogs of Calcipotriol, PRI-2202 and PRI-2205, Against Human HL-60 Leukemia and MCF-7 Breast Cancer Cells

    Directory of Open Access Journals (Sweden)

    Andrzej Kutner

    2013-10-01

    Full Text Available Diastereomeric and geometric analogs of calcipotriol, PRI-2202 and PRI-2205, were synthesized as advanced intermediates from vitamin D C-22 benzothiazoyl sulfones and side-chain aldehydes using our convergent strategy. Calcitriol, calcipotriol (PRI-2201 and tacalcitol (PRI-2191 were used as the reference compounds. Among a series of tested analogs the diastereomeric analog PRI-2202 showed the strongest antiproliferative activity on the human breast cancer cell line MCF-7, whereas the geometric analog PRI-2205 was the weakest. Both analogs were less potent in antiproliferative activity against HL-60 cells compared to the reference compounds. The ability to potentiate antiproliferative effect of cisplatin or doxorubicin against HL-60 cells or that of tamoxifen against the MCF-7 cell line was observed at higher doses of PRI-2202 or PRI-2205 than those of the reference compounds. The proapoptotic activity of tamoxifen, expressed as the diminished mitochondrial membrane potential, as well as the increased phosphatidylserine expression, was partially attenuated by calcitriol, PRI-2191, PRI-2201 and PRI-2205. The treatment of the MCF-7 cells with tamoxifen alone resulted in an increase in VDR expression. Moreover, a further increase in VDR expression was observed when the analogs PRI-2201 or PRI-2205, but not PRI-2191, were used in combination with tamoxifen. This observation could partially explain the potentiation of the antiproliferative effect of tamoxifen by vitamin D analogs.

  19. The metabolic landscape of cancer stem cells.

    Science.gov (United States)

    Dando, Ilaria; Dalla Pozza, Elisa; Biondani, Giulia; Cordani, Marco; Palmieri, Marta; Donadelli, Massimo

    2015-09-01

    Cancer stem cells (CSCs) are a sub-population of quiescent cells endowed with self-renewal properties that can sustain the malignant behavior of the tumor mass giving rise to more differentiated cancer cells. For this reason, the specific killing of CSCs represents one of the most important challenges of the modern molecular oncology. However, their particular resistance to traditional chemotherapy and radiotherapy imposes a thorough understanding of their biological and biochemical features. The metabolic peculiarities of CSCs may be a therapeutic and diagnostic opportunity in cancer research. In this review, we summarize the most significant discoveries on the metabolism of CSCs describing and critically analyzing the studies supporting either glycolysis or mitochondrial oxidative phosphorylation as a primary source of energy for CSCs. PMID:26337609

  20. Glycan Engineering for Cell and Developmental Biology

    Science.gov (United States)

    Griffin, Matthew E.; Hsieh-Wilson, Linda C.

    2016-01-01

    Cell-surface glycans are a diverse class of macromolecules that participate in many key biological processes, including cell-cell communication, development, and disease progression. Thus, the ability to modulate the structures of glycans on cell surfaces provides a powerful means not only to understand fundamental processes but also to direct activity and elicit desired cellular responses. Here, we describe methods to sculpt glycans on cell surfaces and highlight recent successes in which artificially engineered glycans have been employed to control biological outcomes such as the immune response and stem cell fate. PMID:26933739

  1. Lung cancer - non-small cell

    Science.gov (United States)

    Cancer - lung - non-small cell; Non-small cell lung cancer; NSCLC; Adenocarcinoma - lung; Squamous cell carcinoma - lung ... Horn L, Eisenberg R, Gius D, et al. Cancer of the lung. In: Niederhuber JE, Armitage JO, Doroshow JH, Kastan ...

  2. Label-Free Biosensors for Cell Biology

    OpenAIRE

    Ye Fang

    2011-01-01

    Label-free biosensors for studying cell biology have finally come of age. Recent developments have advanced the biosensors from low throughput and high maintenance research tools to high throughput and low maintenance screening platforms. In parallel, the biosensors have evolved from an analytical tool solely for molecular interaction analysis to powerful platforms for studying cell biology at the whole cell level. This paper presents historical development, detection principles, and applicat...

  3. The role of the ALK receptor in cancer biology.

    Science.gov (United States)

    Hallberg, B; Palmer, R H

    2016-09-01

    A vast array of oncogenic variants has been identified for anaplastic lymphoma kinase (ALK). Therefore, there is a need to better understand the role of ALK in cancer biology in order to optimise treatment strategies. This review summarises the latest research on the receptor tyrosine kinase ALK, and how this information can guide the management of patients with cancer that is ALK-positive. A variety of ALK gene alterations have been described across a range of tumour types, including point mutations, deletions and rearrangements. A wide variety of ALK fusions, in which the kinase domain of ALK and the amino-terminal portion of various protein partners are fused, occur in cancer, with echinoderm microtubule-associated protein-like 4 (EML4)-ALK being the most prevalent in non-small-cell lung cancer (NSCLC). Different ALK fusion proteins can mediate different signalling outputs, depending on properties such as subcellular localisation and protein stability. The ALK fusions found in tumours lack spatial and temporal regulation, which can also affect dimerisation and substrate specificity. Two ALK tyrosine kinase inhibitors (TKIs), crizotinib and ceritinib, are currently approved in Europe for use in ALK-positive NSCLC and several others are in development. These ALK TKIs bind slightly differently within the ATP-binding pocket of the ALK kinase domain and are associated with the emergence of different resistance mutation patterns during therapy. This emphasises the need to tailor the sequence of ALK TKIs according to the ALK signature of each patient. Research into the oncogenic functions of ALK, and fast paced development of ALK inhibitors, has substantially improved outcomes for patients with ALK-positive NSCLC. Limited data are available surrounding the physiological ligand-stimulated activation of ALK signalling and further research is needed. Understanding the role of ALK in tumour biology is key to further optimising therapeutic strategies for ALK

  4. Cancer Stem Cells and Pediatric Solid Tumors

    International Nuclear Information System (INIS)

    Recently, a subpopulation of cells, termed tumor-initiating cells or tumor stem cells (TSC), has been identified in many different types of solid tumors. These TSC, which are typically more resistant to chemotherapy and radiation compared to other tumor cells, have properties similar to normal stem cells including multipotency and the ability to self-renew, proliferate, and maintain the neoplastic clone. Much of the research on TSC has focused on adult cancers. With considerable differences in tumor biology between adult and pediatric cancers, there may be significant differences in the presence, function and behavior of TSC in pediatric malignancies. We discuss what is currently known about pediatric solid TSC with specific focus on TSC markers, tumor microenvironment, signaling pathways, therapeutic resistance and potential future therapies to target pediatric TSC

  5. Comprehensive copy number profiles of breast cancer cell model genomes

    OpenAIRE

    Shadeo, Ashleen; Lam, Wan L.

    2006-01-01

    Introduction Breast cancer is the most commonly diagnosed cancer in women worldwide and consequently has been extensively investigated in terms of histopathology, immunochemistry and familial history. Advances in genome-wide approaches have contributed to molecular classification with respect to genomic changes and their subsequent effects on gene expression. Cell lines have provided a renewable resource that is readily used as model systems for breast cancer cell biology. A thorough characte...

  6. Metabolic alterations in cancer cells and therapeutic implications

    Institute of Scientific and Technical Information of China (English)

    Naima Hammoudi; Kausar Begam Riaz Ahmed; Celia Garcia-Prieto; Peng Huang

    2011-01-01

    Cancer metabolism has emerged as an important area of research in recent years. Elucidation of the metabolic differences between cancer and normal cells and the underlying mechanisms will not only advance our understanding of fundamental cancer cell biology but also provide an important basis for the development of new therapeutic strategies and novel compounds to selectively eliminate cancer cells by targeting their unique metabolism. This article reviews several important metabolic alterations in cancer cells, with an emphasis on increased aerobic glycolysis (the Warburg effect) and glutamine addiction, and discusses the mechanisms that may contribute to such metabolic changes. In addition, metabolic alterations in cancer stem cells, mitochondrial metabolism and its influence on drug sensitivity, and potential therapeutic strategies and agents that target cancer metabolism are also discussed.

  7. Cell-to-cell variability in cell death: can systems biology help us make sense of it all?

    OpenAIRE

    Xia, X; Owen, M. S.; Lee, R E C; Gaudet, S

    2014-01-01

    One of the most common observations in cell death assays is that not all cells die at the same time, or at the same treatment dose. Here, using the perspective of the systems biology of apoptosis and the context of cancer treatment, we discuss possible sources of this cell-to-cell variability as well as its implications for quantitative measurements and computational models of cell death. Many different factors, both within and outside of the apoptosis signaling networks, have been correlated...

  8. Quasi – biological model of radiogenic cancer morbidity

    Directory of Open Access Journals (Sweden)

    A. T. Gubin

    2016-01-01

    Full Text Available The methods: Linear differential equations were used to formalize contemporary assumptions of self –sustaining tissue cell kinetics under the impact of adverse factors, on the formation and repairing of cell “pre-cancer” defects, on inheritance and retaining such defects in daughter cells which results in malignant neoplasms, on age-dependent impairment of human body’s function to eliminate such cells.The results: The model reproduces the well-known regularities of radiogenic cancer morbidity increase depending on instantaneous radiation exposure age and on attained age: the relative reduction at increased radiation age which the model attributes to age decrease of stem cells, relative reduction at increased time after radiation induced by “sorting out” of cells with “pre-cancer” defects, absolute increase with age proportional to natural cause mortality rate.The relevance of the developed quasi-biological model is displayed via comparison to the ICRP model for radiogenic increase of solid carcinomas’ morbidity after single radiation exposure. The latter model had been developed after Japanese cohort observations. For both genders high goodness-of-fit was achieved between the models at values of Gompertz’ law factor which had been defined for men and women in this cohort via selecting the value of the only free parameter indicating age-dependent exponential retardation of stem cells’ division.The conclusion: The proposed model suggests that the estimation of radiogenic risk inter-population transfer can be done on the basis of the data on age-dependent mortality intensity increase from all natural causes. The model also creates the premises for inter-species transfer of risk following the well-known parameters of cell populations’ kinetics in animal’s organs and tissues and Gompertz’s law parameters. This model is applicable also for analyses of age-dependent changes of background cancer morbidity. 

  9. Effect of polyethyleneglycol (PEG) chain length on the bio-nano-interactions between PEGylated lipid nanoparticles and biological fluids: from nanostructure to uptake in cancer cells

    Science.gov (United States)

    Pozzi, Daniela; Colapicchioni, Valentina; Caracciolo, Giulio; Piovesana, Susy; Capriotti, Anna Laura; Palchetti, Sara; de Grossi, Stefania; Riccioli, Anna; Amenitsch, Heinz; Laganà, Aldo

    2014-02-01

    When nanoparticles (NPs) enter a physiological environment, medium components compete for binding to the NP surface leading to formation of a rich protein shell known as the ``protein corona''. Unfortunately, opsonins are also adsorbed. These proteins are immediately recognized by the phagocyte system with rapid clearance of the NPs from the bloodstream. Polyethyleneglycol (PEG) coating of NPs (PEGylation) is the most efficient anti-opsonization strategy. Linear chains of PEG, grafted onto the NP surface, are able to create steric hindrance, resulting in a significant inhibition of protein adsorption and less recognition by macrophages. However, excessive PEGylation can lead to a strong inhibition of cellular uptake and less efficient binding with protein targets, reducing the potential of the delivery system. To reach a compromise in this regard we employed a multi-component (MC) lipid system with uncommon properties of cell uptake and endosomal escape and increasing length of PEG chains. Nano liquid chromatography coupled with tandem mass spectrometry (nanoLC-MS/MS) analysis allowed us to accurately determine the corona composition showing that apolipoproteins are the most abundant class in the corona and that increasing the PEG length reduced the protein adsorption and the liposomal surface affinity for apolipoproteins. Due to the abundance of apolipoproteins, we exploited the ``protein corona effect'' to deliver cationic liposome-human plasma complexes to human prostate cancer PC3 cells that express a high level of scavenger receptor class B type 1 in order to evaluate the cellular uptake efficiency of the systems used. Combining laser scanning confocal microscopy with flow cytometry analysis in PC3 cells we demonstrated that MC-PEG2k is the best compromise between an anti-opsonization strategy and active targeting and could be a promising candidate to treat prostate cancer in vivo.When nanoparticles (NPs) enter a physiological environment, medium components

  10. Breast Cancer Biology and Ethnic Disparities in Breast Cancer Mortality in New Zealand: A Cohort Study

    OpenAIRE

    Seneviratne, Sanjeewa; Lawrenson, Ross; Scott, Nina; Kim, Boa; Shirley, Rachel; Campbell, Ian

    2015-01-01

    Introduction Indigenous Māori women have a 60% higher breast cancer mortality rate compared with European women in New Zealand. We investigated differences in cancer biological characteristics and their impact on breast cancer mortality disparity between Māori and NZ European women. Materials and Methods Data on 2849 women with primary invasive breast cancers diagnosed between 1999 and 2012 were extracted from the Waikato Breast Cancer Register. Differences in distribution of cancer biologica...

  11. Piperlongumine exerts cytotoxic effects against cancer cells with mutant p53 proteins at least in part by restoring the biological functions of the tumor suppressor.

    Science.gov (United States)

    Basak, Debasish; Punganuru, Surendra R; Srivenugopal, Kalkunte S

    2016-04-01

    Piperlongumine (PL), a small molecule alkaloid present in black pepper (Piper longum), has been reported to kill tumor cells irrespective of their p53 gene status, however, the mechanisms involved are unknown. Since p53 is a redox-sensitive protein, we hypothesized that the redox imbalance induced by PL may affect the structure and/or function of the mutant p53 protein and promote cell death. We used two human colon cancer cell lines, the HT29 and SW620 which harbor the R273H DNA contact abrogatory mutation in p53. PL treatment induced significant ROS production and protein glutathionylation with a concomitant increase in Nrf-2 expression in both cell lines. Surprisingly, immunoprecipitation with wt-p53 specific antibodies (PAb1620) or direct western blotting showed a progressive generation of wild-type-like p53 protein along with a loss of its mutant counterpart in PL-treated HT29 and SW620 cells. Moreover, the EMSA and DNA-affinity blotting revealed a time-dependent restoration of DNA-binding for the mutant p53, which was accompanied by the induction of p53 target genes, MDM2 and Bax. PL, while cytotoxic by itself, also increased the cell killing by many anticancer drugs. In nude mice bearing the HT29 tumors, PL alone (7.5 mg/kg daily) produced a 40% decrease in tumor volume, which was accompanied by diminished intratumoral mutant p53 protein levels. The antitumor efficacy of BCNU or doxorubicin in HT29 xenografts was highly potentiated by PL, followed by expression of apoptotic proteins. These clinically-relevant findings suggest that PL-induced oxidative milieu facilitates a weak functional restoration of mutant p53 through protein glutathionylation and contributes to the increased drug sensitivity. PMID:26848023

  12. Chemical approaches to studying stem cell biology

    Institute of Scientific and Technical Information of China (English)

    Wenlin Li; Kai Jiang; Wanguo Wei; Yan Shi; Sheng Ding

    2013-01-01

    Stem cells,including both pluripotent stem cells and multipotent somatic stem cells,hold great potential for interrogating the mechanisms of tissue development,homeostasis and pathology,and for treating numerous devastating diseases.Establishment of in vitro platforms to faithfully maintain and precisely manipulate stem cell fates is essential to understand the basic mechanisms of stem cell biology,and to translate stem cells into regenerative medicine.Chemical approaches have recently provided a number of small molecules that can be used to control cell selfrenewal,lineage differentiation,reprogramming and regeneration.These chemical modulators have been proven to be versatile tools for probing stem cell biology and manipulating cell fates toward desired outcomes.Ultimately,this strategy is promising to be a new frontier for drug development aimed at endogenous stem cell modulation.

  13. Drug Treatment of Cancer Cell Lines: A Way to Select for Cancer Stem Cells?

    Energy Technology Data Exchange (ETDEWEB)

    Chiodi, Ilaria; Belgiovine, Cristina; Donà, Francesca; Scovassi, A. Ivana; Mondello, Chiara, E-mail: mondello@igm.cnr.it [Institute of Molecular Genetics, CNR, via Abbiategrasso 207, 27100 Pavia (Italy)

    2011-03-04

    Tumors are generally composed of different cell types. In recent years, it has been shown that in many types of cancers a subset of cells show peculiar characteristics, such as the ability to induce tumors when engrafted into host animals, self-renew and being immortal, and give rise to a differentiated progeny. These cells have been defined as cancer stem cells (CSCs) or tumor initiating cells. CSCs can be isolated both from tumor specimens and established cancer cell lines on the basis of their ability to exclude fluorescent dyes, express specific cell surface markers or grow in particular culture conditions. A key feature of CSCs is their resistance to chemotherapeutic agents, which could contribute to the remaining of residual cancer cells after therapeutic treatments. It has been shown that CSC-like cells can be isolated after drug treatment of cancer cell lines; in this review, we will describe the strategies so far applied to identify and isolate CSCs. Furthermore, we will discuss the possible use of these selected populations to investigate CSC biology and develop new anticancer drugs.

  14. Drug Treatment of Cancer Cell Lines: A Way to Select for Cancer Stem Cells?

    International Nuclear Information System (INIS)

    Tumors are generally composed of different cell types. In recent years, it has been shown that in many types of cancers a subset of cells show peculiar characteristics, such as the ability to induce tumors when engrafted into host animals, self-renew and being immortal, and give rise to a differentiated progeny. These cells have been defined as cancer stem cells (CSCs) or tumor initiating cells. CSCs can be isolated both from tumor specimens and established cancer cell lines on the basis of their ability to exclude fluorescent dyes, express specific cell surface markers or grow in particular culture conditions. A key feature of CSCs is their resistance to chemotherapeutic agents, which could contribute to the remaining of residual cancer cells after therapeutic treatments. It has been shown that CSC-like cells can be isolated after drug treatment of cancer cell lines; in this review, we will describe the strategies so far applied to identify and isolate CSCs. Furthermore, we will discuss the possible use of these selected populations to investigate CSC biology and develop new anticancer drugs

  15. Breast cancer stem cell markers – the rocky road to clinical applications

    OpenAIRE

    Dontu, Gabriela

    2008-01-01

    Lately, understanding the role of cancer stem cells in tumor initiation and progression became a major focus in stem cell biology and in cancer research. Considerable efforts, such as the recent studies by Honeth and colleagues, published in the June issue of Breast Cancer Research, are directed towards developing clinical applications of the cancer stem cell concepts. This work shows that the previously described CD44+CD24- stem cell phenotype is associated with basal-type breast cancers in ...

  16. Cancer Stem Cells: From Identification To Eradication

    International Nuclear Information System (INIS)

    A fundamental problem in cancer research is identification of the cells within a tumor that sustain the growth of the neoplastic clone. The concept that only a subpopulation of rare cancer stem cells (CSCs) is responsible for maintenance of the neoplasm emerged nearly 50 years ago: however, conclusive proof for the existence of a CSC was obtained only relatively recently. As definition, cancer stem cells (CSCs) are a sub-population of cancer cells (found within solid tumors or hematological malignancies) that possess characteristics normally associated with stem cells as high self-renewal potential. These cells are believed to be tumorige forming) in contrast to the bulk of cancer cells, which are thought to be non-tumorigenic. The first conclusive evidence for CSCs was published in 1997 in Nature Medicine by Bonnet and Dick who isolated a subpopulation of leukemic cells in AML that express a specific surface marker CD34 but lacks the CD38 marker. The authors established that the CD34+/CD38– subpopulation is capable of initiating leukemia in NOD/SCID mice that is histologically similar to the donor [1]. This subpopulation of cells is termed SCID Leukemia-initiating cells (SLIC). A theory suggests that such cells act as a reservoir for disease recurrence, are the origin of metastasis and exert resistance towards classical antitumor regimens. This resistance was attributed to a combination of several factors [2], suggesting that conventional antitumor regimens are targeting the bulk of the tumor not the dormant stubborn CSCs. Purpose Better understanding of the leukemogenic process and the biology of CSCS to define the most applicable procedures for their identification and isolation in order to design specific targeted therapies aiming at reducing disease burden to very low levels .. up to eradication of the tumor

  17. Construction and Influence of Human Nuclear Factor-κB p65 shRNA Lentiviral 
Vector on Malignant Biological Behavior of Lung Cancer Cells

    Directory of Open Access Journals (Sweden)

    Hongjuan GUO

    2014-05-01

    Full Text Available Background and objective Nuclear factor-κB is an important transcription factor and is closely associated with a variety of malignant tumors. The biological behavior of lung tumor cells can be reversed by inhibiting the expression of NF-κBp65 directly or indirectly. Nuclear factor-κBp65 gene shRNA recombinant plasmids were constructed and then infected with A549 cells. New stable cell lines were selected, and the ability of migration and adhesion was identified. Methods Both scramble control sequence and interference sequence (shRNA of human nuclear factor-κBp65 were designed and synthesized to build recombinant plasmids, with BamH I site at the 5′ end and Xho I and EcoR I sites at the 3′ end. A549 cells were infected, and stable transfection strains were selected by puromycin. Western blot and qRT-PCR methods were applied to assess the interference efficient of NF-κBp65 and the protein expression level of IκBα. Transwell and MTT assays were carried out to analyze the ability of migration and adhesion of A549 cells separately. Results Recombinant plasmids were successfully built, and A549/NF-κB p65 scramble and A549/NF-κB p65 shRNA stable transfection strains were also successfully screened. Both mRNA and protein expression levels of NF-κBp65 showed that A549/NF-κBp65 shRNA cells decreased compared with A549/NF-κB p65 scramble cells and A549 cells, whereas the protein level of IκBα significantly increased. Both migration and adhesion abilities were also reduced. Conclusion In this study, both mRNA and protein expression levels of NF-κBp65 were effectively suppressed by RNA interference technique. NF-κBp65 inhibition can significantly reduce the migration and adhesion ability of A549 cells.

  18. Neuroendocrine differentiation of prostate cancer cells

    Czech Academy of Sciences Publication Activity Database

    Pernicová, Zuzana; Lincová, Eva; Staršíchová, Andrea; Kozubík, Alois; Souček, Karel

    Budapest, 2008. s. 194. [ISAC XXIV International Congress, Cytometry in the Age of Systems Biology. 17.05.2008-21.05.2008, Budapest] R&D Projects: GA ČR(CZ) GA204/07/0834 Institutional research plan: CEZ:AV0Z50040507; CEZ:AV0Z50040702 Keywords : neuroendocrine differentiation * neuroendocrine-like cells * prostate cancer Subject RIV: BO - Biophysics

  19. Diet & Cancer: An Update for Biology Teachers.

    Science.gov (United States)

    Anastasiou, Clifford J.

    1988-01-01

    Reports on dietary substances which act against cancer-causing agents. Indicates that adapting a lifestyle which combines reduced fat intake with increased fiber-containing foods will reduce the risk of some common cancers. Provides teaching strategies and activities to help students analyze their lifestyles for a reduction in cancer risk. (RT)

  20. Mouse models for cancer stem cell research

    OpenAIRE

    Cheng, Le; Ramesh, Anirudh V.; Flesken-Nikitin, Andrea; Choi, Jinhyang; Nikitin, Alexander Yu.

    2009-01-01

    Cancer stem cell concept assumes that cancers are mainly sustained by a small pool of neoplastic cells, known as cancer stem cells or tumor initiating cells, which are able to reproduce themselves and produce phenotypically heterogeneous cells with lesser tumorigenic potential. Cancer stem cells represent an appealing target for development of more selective and efficient therapies. However, direct testing of the cancer stem cell concept and assessment of its therapeutic implications in human...

  1. The circadian clock and cell cycle: Interconnected biological circuits

    OpenAIRE

    Masri, Selma; Cervantes, Marlene; Sassone-Corsi, Paolo

    2013-01-01

    The circadian clock governs biological timekeeping on a systemic level, helping to regulate and maintain physiological processes, including endocrine and metabolic pathways with a periodicity of 24-hours. Disruption within the circadian clock machinery has been linked to numerous pathological conditions, including cancer, suggesting that clock-dependent regulation of the cell cycle is an essential control mechanism. This review will highlight recent advances on the ‘gating’ controls of the ci...

  2. Transport processes in biological systems: Tumoral cells and human brain

    Science.gov (United States)

    Lucia, Umberto

    2014-01-01

    The entropy generation approach has been developed for the analysis of complex systems, with particular regards to biological systems, in order to evaluate their stationary states. The entropy generation is related to the transport processes related to exergy flows. Moreover, cancer can be described as an open complex dynamic and self-organizing system. Consequently, it is used as an example useful to evaluate the different thermo-chemical quantities of the transport processes in normal and in tumoral cells systems.

  3. Tumor-initiating label-retaining cancer cells in human gastrointestinal cancers undergo asymmetric cell division.

    Science.gov (United States)

    Xin, Hong-Wu; Hari, Danielle M; Mullinax, John E; Ambe, Chenwi M; Koizumi, Tomotake; Ray, Satyajit; Anderson, Andrew J; Wiegand, Gordon W; Garfield, Susan H; Thorgeirsson, Snorri S; Avital, Itzhak

    2012-04-01

    Label-retaining cells (LRCs) have been proposed to represent adult tissue stem cells. LRCs are hypothesized to result from either slow cycling or asymmetric cell division (ACD). However, the stem cell nature and whether LRC undergo ACD remain controversial. Here, we demonstrate label-retaining cancer cells (LRCCs) in several gastrointestinal (GI) cancers including fresh surgical specimens. Using a novel method for isolation of live LRCC, we demonstrate that a subpopulation of LRCC is actively dividing and exhibits stem cells and pluripotency gene expression profiles. Using real-time confocal microscopic cinematography, we show live LRCC undergoing asymmetric nonrandom chromosomal cosegregation LRC division. Importantly, LRCCs have greater tumor-initiating capacity than non-LRCCs. Based on our data and that cancers develop in tissues that harbor normal-LRC, we propose that LRCC might represent a novel population of GI stem-like cancer cells. LRCC may provide novel mechanistic insights into the biology of cancer and regenerative medicine and present novel targets for cancer treatment. PMID:22331764

  4. Biological synthesis of silver nanoparticles using the fungus Humicola sp. and evaluation of their cytoxicity using normal and cancer cell lines

    Science.gov (United States)

    Syed, Asad; Saraswati, Supriya; Kundu, Gopal C.; Ahmad, Absar

    2013-10-01

    Nanoscience is a new born science of the modern era and taps into the potential of particles at nanoscale. Bulk materials reduced to nanoscale dimensions thus obtain unique properties such as electronic, optical, magnetic and chemical. As far as synthesis of nanoparticles is concerned, biological synthesis has recently sparked a great interest as compared to other available chemical and physical methods on account of its eco-friendliness and cost-effectiveness. Here we report, for the first time, the biosynthesis of silver nanoparticles by the thermophilic fungus Humicola sp. The fungus when reacted with Ag+ ions reduces the precursor solution and leads to the formation of extracellular nanoparticles as monitored by ultra violet visible spectroscopy (UV-Vis). The morphology of nanoparticles is found to be spherical with good dispersity as revealed by transmission electron microscopy (TEM). Cell viability assays were carried out to assess the cytotoxicity of silver nanoparticles on NIH3T3 mouse embryonic fibroblast cell line and MDA-MB-231 human breast carcinoma cell line.

  5. Eradicating cancer cells: struggle with a chameleon

    OpenAIRE

    Di, Jiabo; Boer, Tjitske Duiveman-de; Figdor, Carl G.; Torensma, Ruurd

    2011-01-01

    Eradication of cancer stem cells to abrogate tumor growth is a new treatment modality. However, like normal cells cancer cells show plasticity. Differentiated tumor stem cells can acquire stem cell properties when they gain access to the stem cell niche. This indicates that eradicating of stem cells (emptying of the niche) alone will not lead to eradication of the tumor. Treatment should be directed to cancer stem cells ànd more mature cancer cells.

  6. Use of Animation in Teaching Cell Biology

    OpenAIRE

    Stith, Bradley J.

    2004-01-01

    To address the different learning styles of students, and because students can access animation from off-campus computers, the use of digital animation in teaching cell biology has become increasingly popular. Sample processes from cell biology that are more clearly presented in animation than in static illustrations are identified. The value of animation is evaluated on whether the process being taught involves motion, cellular location, or sequential order of numerous events. Computer progr...

  7. Mutant p53: Multiple Mechanisms Define Biologic Activity in Cancer

    OpenAIRE

    Kim, Michael Paul; Zhang, Yun; Lozano, Guillermina

    2015-01-01

    The functional importance of p53 as a tumor suppressor gene is evident through its pervasiveness in cancer biology. The p53 gene is the most commonly altered gene in human cancer; however, not all genetic alterations are biologically equivalent. The majority of alterations involve p53 missense mutations that result in the production of mutant p53 proteins. Such mutant p53 proteins lack normal p53 function and may concomitantly gain novel functions, often with deleterious effects. Here, we rev...

  8. Biology-driven cancer drug development: back to the future

    OpenAIRE

    Ashworth Alan; Lord Christopher J

    2010-01-01

    Abstract Most of the significant recent advances in cancer treatment have been based on the great strides that have been made in our understanding of the underlying biology of the disease. Nevertheless, the exploitation of biological insight in the oncology clinic has been haphazard and we believe that this needs to be enhanced and optimized if patients are to receive maximum benefit. Here, we discuss how research has driven cancer drug development in the past and describe how recent advances...

  9. The Evolving Concepts of Cancer Stem Cells in Head and Neck Squamous Cell Carcinoma

    OpenAIRE

    Amit Shah; Shilpa Patel; Jigna Pathak; Niharika Swain; Shwetha Kumar

    2014-01-01

    There is increasing evidence that the growth and spread of cancers is driven by a small subpopulation of cancer stem cells (CSCs)—the only cells that are capable of long-term self-renewal and generation of the phenotypically diverse tumor cell population. CSCs have been identified and isolated in a variety of human cancers including head and neck squamous cell carcinoma (HNSCC). The concept of cancer stem cells may have profound implications for our understanding of tumor biology and for the ...

  10. The cell biology of T-dependent B cell activation

    DEFF Research Database (Denmark)

    Owens, T; Zeine, R

    1989-01-01

    The requirement that CD4+ helper T cells recognize antigen in association with class II Major Histocompatibility Complex (MHC) encoded molecules constrains T cells to activation through intercellular interaction. The cell biology of the interactions between CD4+ T cells and antigen-presenting cells...

  11. Analysis of single biological cells

    International Nuclear Information System (INIS)

    The extraction of elemental information from single cultured cells using nuclear microscopy is an area of great potential because it can provide both quantitative information on the uptake of elements by the cell, and also its elemental response to a wide variety of external stimuli. A recent technique based on nuclear physics technology enables the analysis of single cells down to the parts per million level to be achieved

  12. Teaching Cell Biology in Primary Schools

    Directory of Open Access Journals (Sweden)

    Francele de Abreu Carlan

    2014-01-01

    Full Text Available Basic concepts of cell biology are essential for scientific literacy. However, because many aspects of cell theory and cell functioning are quite abstract, students experience difficulties understanding them. In this study, we investigated whether diverse teaching resources such as the use of replicas of Leeuwenhoek’s microscope, visualization of cells using an optical microscope, construction of three-dimensional cell models, and reading of a comic book about cells could mitigate the difficulties encountered when teaching cell biology to 8th-grade primary school students. The results suggest that these didactic activities improve students’ ability to learn concrete concepts about cell biology, such as the composition of living beings, growth, and cicatrization. Also, the development of skills was observed, as, for example, the notion of cell size. However, no significant improvements were observed in students’ ability to learn about abstract topics, such as the structures of subcellular organelles and their functions. These results suggest that many students in this age have not yet concluded Piaget’s concrete operational stage, indicating that the concepts required for the significant learning of abstract subjects need to be explored more thoroughly in the process of designing programs that introduce primary school students to cell biology.

  13. Deciphering The Complex Biological Interactions Of Nitric Oxide In Cancer

    Directory of Open Access Journals (Sweden)

    S. Perwez Hussain

    2015-08-01

    Full Text Available NO• is a free radical and is involved in a number of critical physiological processes including vasodilation, neurotransmission, immune regulation and inflammation. There are convincing evidence suggesting a role of NO• in the development and progression of different cancer types. However, the role of NO• in tumorigenesis is highly complex and both pro- and anti-neoplastic functions have been reported, which largely depends on the amount of NO•, cell types, cellular microenvironment, its interaction with other reactive species and presence of metals. An interesting interaction occurs between NO• and p53 tumor suppressor, in which NO•-induced DNA damage causes the stabilization and accumulation of p53, which in turn, transrepresses inducible nitric oxide synthase (NOS2 in a negative feedback loop. In chronic inflammatory diseases, for example ulcerative colitis, NO• induces p53 stabilization and the initiation of DNA-damage response pathway, and also generation of p53 mutation and subsequent clonal selection of p53 mutant cells. Genetic deletion of NOS2 in p53-deficient mice can either suppress or enhance lymphomagenesis depending on the inflammatory microenvironment. These findings highlight the importance of understanding the complex biological interaction of NO• in the context of the molecular makeup of each individual cancer to design NO•-targeted treatment strategies.

  14. Biologic correlates and significance of axonogenesis in prostate cancer.

    Science.gov (United States)

    Olar, Adriana; He, Dandan; Florentin, Diego; Ding, Yi; Ayala, Gustavo

    2014-07-01

    Cancer-related axonogenesis and neurogenesis are recently described biologic phenomena. Our previously published data showed that nerve density and the number of neurons in the parasympathetic ganglia are increased in prostate cancer (PCa) and associated with aggressive disease. Tissue microarrays were constructed from 640 radical prostatectomy specimens with PCa. Anti-protein gene product 9.5 (PGP 9.5) antibodies were used to identify and quantify nerve density. Protein expression was objectively analyzed using deconvolution imaging, image segmentation, and image analysis. Data were correlated with clinicopathological variables and tissue biomarkers available in our database. Nerve density, as measured by PGP 9.5 expression, had a weak but significant positive correlation with the lymph node status (ρ = 0.106; P = .0275). By Cox univariate analysis, PGP 9.5 was a predictor of time to biochemical recurrence, but not on multivariate analysis. Increased nerve density correlated with increased proliferation of PCa cells. It also correlated with expression of proteins involved in survival pathways (Phosphorylated alpha serine/threonine-protein kinase, NFκB, GSK-2, PIM-2, c-Myc, SKP-2, SRF, P27n, PTEN), with increased levels of hormonal regulation elements (androgen receptor, estrogen receptor α), and coregulators and repressors (SRC-1, SRC-2, AIB-1, DAX). Axonogenesis is a recently described phenomenon of paramount importance in the biology of PCa. Although the degree of axonogenesis is predictive of aggressive behavior in PCa, it does not add to the information present in current models on multivariate analysis. We present data that corroborate that axonogenesis is involved in biologic processes such as proliferation of PCa, through activation of survival pathways and interaction with hormonal regulation. PMID:24767770

  15. Radiobiological characteristics of cancer stem cells from esophageal cancer cell lines

    OpenAIRE

    Wang, Jian-Lin; Yu, Jing-Ping; Zhi-qiang SUN; Sun, Su-Ping

    2014-01-01

    AIM: To study the cancer stem cell population in esophageal cancer cell lines KYSE-150 and TE-1 and identify whether the resulting stem-like spheroid cells display cancer stem cells and radiation resistance characteristics.

  16. The cell biology of touch

    OpenAIRE

    Lumpkin, Ellen A.; Marshall, Kara L.; Nelson, Aislyn M.

    2010-01-01

    The sense of touch detects forces that bombard the body’s surface. In metazoans, an assortment of morphologically and functionally distinct mechanosensory cell types are tuned to selectively respond to diverse mechanical stimuli, such as vibration, stretch, and pressure. A comparative evolutionary approach across mechanosensory cell types and genetically tractable species is beginning to uncover the cellular logic of touch reception.

  17. Chemotherapy targeting cancer stem cells

    OpenAIRE

    Liu, Haiguang; Lv, Lin; Yang, Kai

    2015-01-01

    Conventional chemotherapy is the main treatment for cancer and benefits patients in the form of decreased relapse and metastasis and longer overall survival. However, as the target therapy drugs and delivery systems are not wholly precise, it also results in quite a few side effects, and is less efficient in many cancers due to the spared cancer stem cells, which are considered the reason for chemotherapy resistance, relapse, and metastasis. Conventional chemotherapy limitations and the cance...

  18. Biological cell controllable patch-clamp microchip

    Science.gov (United States)

    Penmetsa, Siva; Nagrajan, Krithika; Gong, Zhongcheng; Mills, David; Que, Long

    2010-12-01

    A patch-clamp (PC) microchip with cell sorting and positioning functions is reported, which can avoid drawbacks of random cell selection or positioning for a PC microchip. The cell sorting and positioning are enabled by air bubble (AB) actuators. AB actuators are pneumatic actuators, in which air pressure is generated by microheaters within sealed microchambers. The sorting, positioning, and capturing of 3T3 cells by this type of microchip have been demonstrated. Using human breast cancer cells MDA-MB-231 as the model, experiments have been demonstrated by this microchip as a label-free technical platform for real-time monitoring of the cell viability.

  19. Single cancer cell analysis on a chip

    OpenAIRE

    Yang, Yoonsun

    2016-01-01

    Cancer cells in blood may represent “a real time liquid biopsy” through the interrogation of single cancer cells thereby determining the outspread of their heterogeneity and guiding therapy. In this thesis, we focused on single cancer cell analysis downstream of the isolation of cancer cells from blood. We designed and developed various microfluidic devices for genetic and phenotypic characterization of single cancer cells. The limited DNA content in a single cell requires DNA amplification t...

  20. Cell of origin of lung cancer

    OpenAIRE

    Hanna, Jennifer M.; Onaitis, Mark W.

    2013-01-01

    Lung cancer is the leading cause of cancer deaths worldwide, and current therapies are disappointing. Elucidation of the cell(s) of origin of lung cancer may lead to new therapeutics. In addition, the discovery of putative cancer-initiating cells with stem cell properties in solid tumors has emerged as an important area of cancer research that may explain the resistance of these tumors to currently available therapeutics. Progress in our understanding of normal tissue stem cells, tumor cell o...

  1. Head and Neck Cancer Stem Cells

    OpenAIRE

    Krishnamurthy, S.; Nör, J.E.

    2012-01-01

    Most cancers contain a small sub-population of cells that are endowed with self-renewal, multipotency, and a unique potential for tumor initiation. These properties are considered hallmarks of cancer stem cells. Here, we provide an overview of the field of cancer stem cells with a focus on head and neck cancers. Cancer stem cells are located in the invasive fronts of head and neck squamous cell carcinomas (HNSCC) close to blood vessels (perivascular niche). Endothelial cell-initiated signalin...

  2. Control of Apoptosis in Treatment and Biology of Pancreatic Cancer.

    Science.gov (United States)

    Modi, Shrey; Kir, Devika; Banerjee, Sulagna; Saluja, Ashok

    2016-02-01

    Pancreatic cancer is estimated to be the 12th most common cancer in the United States in 2014 and yet this malignancy is the fourth leading cause of cancer-related death in the United States. Late detection and resistance to therapy are the major causes for its dismal prognosis. Apoptosis is an actively orchestrated cell death mechanism that serves to maintain tissue homoeostasis. Cancer develops from normal cells by accruing significant changes through one or more mechanisms, leading to DNA damage and mutations, which in a normal cell would induce this programmed cell death pathway. As a result, evasion of apoptosis is one of the hallmarks of cancer cells. PDAC is notoriously resistant to apoptosis, thereby explaining its aggressive nature and resistance to conventional treatment modalities. The current review is focus on understanding different intrinsic and extrinsic pathways in pancreatic cancer that may affect apoptosis in this disease. PMID:26206252

  3. Establishment and Its Biological Characteristics of Patient-derived Lung Cancer Xenograft Modelse

    Directory of Open Access Journals (Sweden)

    Ying ZHUO

    2010-06-01

    Full Text Available Background and objective With the ongoing need to improve therapy for lung cancer, there has been an increasing interest in the development of reliable preclinical models to test novel therapeutics. The aim of this study is to establish a patient-derived lung cancer xenograft model in mice and to observe the biological characteristics of xenografts. Methods Surgically resectected tumor specimens from patients with lung cancer were implanted in the subcutaneous layer of the NOD/SCID mice. Cancer specimens of percutaneous lung biopsy by CT fluoroscopy were implanted into the subrenal capsule of nude mouse. The subcutaneous carcinoma was surgically removed when it grew to approximately 1.0 cm in diameter, and then re-transplanted into new nude mice. The growth process of transplanted tumor was observed. Expression of CEA, cytokeratin, and Ki67 were detected by immunohistochemistry. Mutations in the exons 18-21 of EGFR and exons 12,59 of K-ras of primary and xenograft tumors were examined. The cell cycle of xenograft tumor cells was analyzed by flow cytometry. Results Eleven cases were conducted for NOD/SCID mice and nude mice modelling. The patient-derived lung cancer xenografts have been established successfully, and the tumor could be passed to new nude mice, including No 2 model (adenocasinoma, No. 3 model (small cell lung cancer, and No. 5 model (squamous cell cancer. High homogeneity was found between xenograft tumors and human lung cancer in histopathology, immunohistochemical phenotype, and EGFR, K-ras mutation status . The S-phase fraction of xenograft cell cycle was prolonged, which indicated that the xenografts remains highly proliferated. Conclusion The xenotransplantation models established for patient-derived lung cancer in immune deficient mice. The success rate is 27%. This model system displayed the biological characteristics of human lung cancer, suggesting that it may provide a stable, reliable, and useful animal model in human

  4. Foxp3 expression in human cancer cells

    Directory of Open Access Journals (Sweden)

    Gourgoulianis Konstantinos I

    2008-04-01

    Full Text Available Abstract Objective Transcription factor forkhead box protein 3 (Foxp3 specifically characterizes the thymically derived naturally occurring regulatory T cells (Tregs. Limited evidence indicates that it is also expressed, albeit to a lesser extent, in tissues other than thymus and spleen, while, very recently, it was shown that Foxp3 is expressed by pancreatic carcinoma. This study was scheduled to investigate whether expression of Foxp3 transcripts and mature protein occurs constitutively in various tumor types. Materials and methods Twenty five tumor cell lines of different tissue origins (lung cancer, colon cancer, breast cancer, melanoma, erythroid leukemia, acute T-cell leukemia were studied. Detection of Foxp3 mRNA was performed using both conventional RT-PCR and quantitative real-time PCR while protein expression was assessed by immunocytochemistry and flow cytometry, using different antibody clones. Results Foxp3 mRNA as well as Foxp3 protein was detected in all tumor cell lines, albeit in variable levels, not related to the tissue of origin. This expression correlated with the expression levels of IL-10 and TGFb1. Conclusion We offer evidence that Foxp3 expression, characterizes tumor cells of various tissue origins. The biological significance of these findings warrants further investigation in the context of tumor immune escape, and especially under the light of current anti-cancer efforts interfering with Foxp3 expression.

  5. Recent advances in hematopoietic stem cell biology

    DEFF Research Database (Denmark)

    Bonde, Jesper; Hess, David A; Nolta, Jan A

    2004-01-01

    made recently in the field of stem cell biology, researchers now have improved tools to define novel populations of stem cells, examine them ex vivo using conditions that promote self-renewal, track them into recipients, and determine whether they can contribute to the repair of damaged tissues......PURPOSE OF REVIEW: Exciting advances have been made in the field of hematopoietic stem cell biology during the past year. This review summarizes recent progress in the identification, culture, and in vivo tracking of hematopoietic stem cells. RECENT FINDINGS: The roles of Wnt and Notch proteins...... in regulating stem cell renewal in the microenvironment, and how these molecules can be exploited in ex vivo stem cell culture, are reviewed. The importance of identification of stem cells using functional as well as phenotypic markers is discussed. The novel field of nanotechnology is then discussed...

  6. Interfacing nanostructures to biological cells

    Energy Technology Data Exchange (ETDEWEB)

    Chen, Xing; Bertozzi, Carolyn R.; Zettl, Alexander K.

    2012-09-04

    Disclosed herein are methods and materials by which nanostructures such as carbon nanotubes, nanorods, etc. are bound to lectins and/or polysaccharides and prepared for administration to cells. Also disclosed are complexes comprising glycosylated nanostructures, which bind selectively to cells expressing glycosylated surface molecules recognized by the lectin. Exemplified is a complex comprising a carbon nanotube functionalized with a lipid-like alkane, linked to a polymer bearing repeated .alpha.-N-acetylgalactosamine sugar groups. This complex is shown to selectively adhere to the surface of living cells, without toxicity. In the exemplified embodiment, adherence is mediated by a multivalent lectin, which binds both to the cells and the .alpha.-N-acetylgalactosamine groups on the nanostructure.

  7. An Audiovisual Program in Cell Biology

    Science.gov (United States)

    Fedoroff, Sergey; Opel, William

    1978-01-01

    A subtopic of cell biology, the structure and function of cell membranes, has been developed as a series of seven self-instructional slide-tape units and tested in five medical schools. Organization of advisers, analysis and definition of objectives and content, and development and evaluation of scripts and storyboards are discussed. (Author/LBH)

  8. Common stemness regulators of embryonic and cancer stem cells

    Institute of Scientific and Technical Information of China (English)

    Christiana; Hadjimichael; Konstantina; Chanoumidou; Natalia; Papadopoulou; Panagiota; Arampatzi; Joseph; Papamatheakis; Androniki; Kretsovali

    2015-01-01

    Pluripotency of embryonic stem cells(ESCs) and induced pluripotent stem cells is regulated by a well characterized gene transcription circuitry. The circuitry is assembled by ESC specific transcription factors, signal trans-ducing molecules and epigenetic regulators. Growing understanding of stem-like cells, albeit of more complex phenotypes, present in tumors(cancer stem cells), provides a common conceptual and research frame-work for basic and applied stem cell biology. In this review, we highlight current results on biomarkers, gene signatures, signaling pathways and epigenetic regulators that are common in embryonic and cancer stem cells. We discuss their role in determining the cell phenotype and finally, their potential use to design next generation biological and pharmaceutical approaches for regenerative medicine and cancer therapies.

  9. DUAL ROLES OF CANCER CELL-EXPRESSED IMMUNOGLOBULINS IN CANCER IMMUNOLOGY

    Directory of Open Access Journals (Sweden)

    Gregory Lee

    2014-01-01

    Full Text Available While the expression of immunoglobulins and T cell receptors on cancer cells has been well-established for decades, the potential roles and mechanisms of action of these cancerous antigen receptors have not been fully elucidated. A monoclonal antibody designated as RP215, which reacts specifically with the carbohydrate-associated epitope located on the heavy chain region of cancerous immunoglobulins and T cell receptors, was used as a unique probe to study the roles of antigen receptors in the immunology of cancer cells. Through extensive cell-based biological and immunological studies, it was found that both anti-antigen receptors and RP215 demonstrated similar actions on the gene regulations involved in the growth/proliferation of cancer cells, as well as on toll-like receptors involved in innate immunity. In addition, RP215-specific cancerous immunoglobulins are believed to capture or neutralize circulating antigen/antibodies which may be harmful to cancer cells within the human body. In contrast to normal B and T cells and their respective receptors in the conventional immune system, cancer cells co-express both immunoglobulins and T cell receptors and immune protection is exercised by unique mechanisms. For example, these cancer cell-expressed antigen receptors display a lack of class switching, limited hyper-mutation, aberrant glycosylations and a strong influence on the toll-like receptors of cancer cells. Therefore, it is hypothesized that both normal and cancerous immune systems may co-exist and operate simultaneously within the human body. The balance of these two immune factors for respective surveillance and protection may be relevant to the outcome of cancer immunotherapy in humans. A potential therapeutic strategy is being developed by using RP215 as a drug candidate to target cancer cells based on these observations.

  10. Effects of space flight exposure on cell growth, tumorigenicity and gene expression in cancer cells

    Science.gov (United States)

    Yang, Cheng; Li, Yuehui; Zhang, Zhijie; Luo, Chen; Tong, Yongqing; Zhou, Guohua; Xie, Pingli; Hu, Jinyue; Li, Guancheng

    2008-12-01

    It is well recognized that harsh outer space environment, consisting of microgravity and radiation, poses significant health risks for human cells. To investigate potential effects of the space environment exposure on cancer cells we examined the biological changes in Caski cells carried by the "Shen Zhou IV" spaceship. After exposure for 7 days in spaceflight, 1440 survival subclonal cell lines were established and 4 cell lines were screened. 44F10 and 17E3 were selected because of their increased cell proliferation and tumorigenesis, while 48A9 and 31F2 had slower cytological events. Experiments with cell proliferation assay, flow cytometry, soft agar assay, tumorigenesis assay and DNA microarray analysis have shown that selected cell lines presented multiple biological changes in cell morphology, cell growth, tumorigenicity and gene expression. These results suggest that space environment exposure can make significant biological impact on cancer cells and provide an entry point to find the immunological target of tumorigenesis.

  11. Cancer stem cells, metabolism, and therapeutic significance.

    Science.gov (United States)

    Yang, Mengqi; Liu, Panpan; Huang, Peng

    2016-05-01

    Cancer stem cells (CSCs) have attracted much attention of the research community in the recent years. Due to their highly tumorigenic and drug-resistant properties, CSCs represent important targets for developing novel anticancer agents and therapeutic strategies. CSCs were first described in hematopoietic malignancies and subsequently identified in various types of solid tumors including brain, breast, lung, colon, melanoma, and ovarian cancer. CSCs possess special biological properties including long-term self-renewal capacity, multi-lineage differentiation, and resistance to conventional chemotherapy and radiotherapy. As such, CSCs are considered as a major source of residual disease after therapy leading to disease occurrence. Thus, it is very important to understand the cellular survival mechanisms specific to CSCs and accordingly develop effective therapeutic approaches to eliminate this subpopulation of cancer cells in order to improve the treatment outcome of cancer patients. Possible therapeutic strategies against CSCs include targeting the self-renewal pathways of CSCs, interrupting the interaction between CSCs and their microenvironment, and exploiting the unique metabolic properties of CSCs. In this review article, we will provide an overview of the biological characteristics of CSCs, with a particular focus on their metabolic properties and potential therapeutic strategies to eliminate CSCs. PMID:26864589

  12. 肺癌干细胞生物学特性研究进展%Research advancement on biological characteristics of lung cancer stem cells

    Institute of Scientific and Technical Information of China (English)

    安世民; 丁旭苹; 朱亮

    2014-01-01

    肺癌是具有高度侵袭性的一类恶性肿瘤,传统以手术结合放化疗的治疗手段对肺癌的治疗效果不佳,5年生存率仅为20%~30%,其中重要原因之一是肺癌容易转移与复发.在与肺癌长期斗争的过程中,人们发现肺癌组织中存在一小群肺癌干细胞(lung cancer stem cells,LCSCs),它们是肺癌难以治愈和复发的根本原因.从LCSCs的发现、相关的生物学特性和信号转导通路,以及LCSCs与表皮-间质转化(epithelial-mesenchymal transition,EMT)之间的关系等方面对LSCSs进行综述.

  13. Cancer Stem Cell Hypothesis: Implication for Cancer Prevention and Treatment

    OpenAIRE

    Anna Meiliana; Nurrani Mustika Dewi; Andi Wijaya

    2016-01-01

    BACKGROUND: Cancer is a disease of genomic instability, evasion of immune cells, and adaptation of the tumor cells to the changing environment. Genetic heterogeneity caused by tumors and tumor microenvironmental factors forms the basis of aggressive behavior of some cancer cell populations. CONTENT: Cancers arise in self-renewing cell populations and that the resulting cancers, like their normal organ counterparts, are composed of hierarchically organized cell populations. Self–renewing “...

  14. Procathepsin D and cancer: From molecular biology to clinical applications

    OpenAIRE

    Vetvicka, Vaclav; Vashishta, Aruna; Saraswat-Ohri, Sujata; Vetvickova, Jana

    2010-01-01

    Procathepsin D (pCD) is overexpressed and secreted by cells of various tumor types including breast and lung carcinomas. pCD affects multiple features of tumor cells including proliferation, invasion, metastases and apoptosis. Several laboratories have previously shown that the mitogenic effect of pCD on cancer cells is mediated via its propeptide part (APpCD). However, the exact mechanism of how pCD affects cancer cells has not been identified. Recent observations have also revealed the poss...

  15. Cell biology experiments conducted in space

    Science.gov (United States)

    Taylor, G. R.

    1977-01-01

    A review of cell biology experiments conducted during the first two decades of space flight is provided. References are tabulated for work done with six types of living test system: isolated viruses, bacteriophage-host, bacteria, yeasts and filamentous fungi, protozoans, and small groups of cells (such as hamster cell tissue and fertilized frog eggs). The general results of studies involving the survival of cells in space, the effect of space flight on growing cultures, the biological effects of multicharged high-energy particles, and the effects of space flight on the genetic apparatus of microorganisms are summarized. It is concluded that cell systems remain sufficiently stable during space flight to permit experimentation with models requiring a fixed cell line during the space shuttle era.

  16. Prostate Cancer Stem Cells: Research Advances

    OpenAIRE

    Dagmara Jaworska; Wojciech Król; Ewelina Szliszka

    2015-01-01

    Cancer stem cells have been defined as cells within a tumor that possesses the capacity to self-renew and to cause the heterogeneous lineages of cancer cells that comprise the tumor. Experimental evidence showed that these highly tumorigenic cells might be responsible for initiation and progression of cancer into invasive and metastatic disease. Eradicating prostate cancer stem cells, the root of the problem, has been considered as a promising target in prostate cancer treatment to improve th...

  17. Cell biology of mitotic recombination

    DEFF Research Database (Denmark)

    Lisby, Michael; Rothstein, Rodney

    2015-01-01

    Homologous recombination provides high-fidelity DNA repair throughout all domains of life. Live cell fluorescence microscopy offers the opportunity to image individual recombination events in real time providing insight into the in vivo biochemistry of the involved proteins and DNA molecules as w...

  18. BIOLOGICALLY INSPIRED HARDWARE CELL ARCHITECTURE

    DEFF Research Database (Denmark)

    2010-01-01

    Disclosed is a system comprising: - a reconfigurable hardware platform; - a plurality of hardware units defined as cells adapted to be programmed to provide self-organization and self-maintenance of the system by means of implementing a program expressed in a programming language defined as DNA...

  19. Measuring cell identity in noisy biological systems

    OpenAIRE

    Birnbaum, Kenneth D; Kussell, Edo

    2011-01-01

    Global gene expression measurements are increasingly obtained as a function of cell type, spatial position within a tissue and other biologically meaningful coordinates. Such data should enable quantitative analysis of the cell-type specificity of gene expression, but such analyses can often be confounded by the presence of noise. We introduce a specificity measure Spec that quantifies the information in a gene's complete expression profile regarding any given cell type, and an uncertainty me...

  20. Cancer Stem Cells: Foe or Reprogrammable Cells for Efficient Cancer Therapy?

    Directory of Open Access Journals (Sweden)

    Carlo Ventura

    2015-11-01

    Full Text Available Embryonic development and carcinogenesis share many molecular pathways and regulatory molecules. While the induction of a pluripotent state involves a significant oncogenic risk, as in induced pluripotent stem cells (iPSCs, the embryonic environment in vivo has been shown to suppress tumor development. In this review, we discuss the subtle equilibrium between the nanotopography (niche of the hosting tissue resident stem cells and their biological dynamics, including the transformation in cancer stem cells. We review consistent findings indicating the potential for modulating the biology of human cancer stem cells by the aid of naturally occurring or synthetic molecules, including developmental stage zebrafish embryo extracts, hyaluronan, butyric acid (BA and retinoic acid (RA, hyaluronan mixed esters of BA and RA, melatonin, vitamin D3, and endorphin peptides. Within this context, we dissect the multifaceted mechanisms orchestrated by endorphinergic systems, including paracrine cellto- cell communication, as well as the establishment of autocrine and intracrine (intracellular peptide actions driving transcriptional responses and self-sustaining loops that behave as long-lived signals imparting features characteristic of differentiation, growth regulation and cell memory. Based upon the remarkable action of electromagnetic fields and mechanical vibration on (stem cell signaling, differentiation, and senescence, we also consider the potential for using these physical energies as a tool to afford a fine tuning of cancer stem cell fate. On the whole, we forecast future deployment of the physical and/or chemical approaches described herein aiming at reprogramming, rather than destroying cancer stem cells, eventually placing cancer therapy within the context of Regenerative Medicine.

  1. Adoptive T cell therapy: Addressing challenges in cancer immunotherapy

    Directory of Open Access Journals (Sweden)

    Yee Cassian

    2005-04-01

    Full Text Available Abstract Adoptive T cell therapy involves the ex vivo selection and expansion of effector cells for the treatment of patients with cancer. In this review, the advantages and limitations of using antigen-specific T cells are discussed in counterpoint to vaccine strategies. Although vaccination strategies represent more readily available reagents, adoptive T cell therapy provides highly selected T cells of defined phenotype, specificity and function that may influence their biological behavior in vivo. Adoptive T cell therapy offers not only translational opportunities but also a means to address fundamental issues in the evolving field of cancer immunotherapy.

  2. Common stemness regulators of embryonic and cancer stem cells

    OpenAIRE

    Hadjimichael, Christiana; Chanoumidou, Konstantina; Papadopoulou, Natalia; Arampatzi, Panagiota; Papamatheakis, Joseph; Kretsovali, Androniki

    2015-01-01

    Pluripotency of embryonic stem cells (ESCs) and induced pluripotent stem cells is regulated by a well characterized gene transcription circuitry. The circuitry is assembled by ESC specific transcription factors, signal transducing molecules and epigenetic regulators. Growing understanding of stem-like cells, albeit of more complex phenotypes, present in tumors (cancer stem cells), provides a common conceptual and research framework for basic and applied stem cell biology. In this review, we h...

  3. Integrative computational biology for cancer research

    OpenAIRE

    Fortney, Kristen; Jurisica, Igor

    2011-01-01

    Over the past two decades, high-throughput (HTP) technologies such as microarrays and mass spectrometry have fundamentally changed clinical cancer research. They have revealed novel molecular markers of cancer subtypes, metastasis, and drug sensitivity and resistance. Some have been translated into the clinic as tools for early disease diagnosis, prognosis, and individualized treatment and response monitoring. Despite these successes, many challenges remain: HTP platforms are often noisy and ...

  4. Microsystems for biological cell characterization

    OpenAIRE

    Rissanen, Anna

    2012-01-01

    This thesis describes three techniques for the characterization of living cells using micro-electro-mechanical systems (MEMS) based devices. The study of cellular function and structure is essential for bioprocess control, disease diagnosis, patient treatment and drug discovery. Microsystem technology enables characterization of very small samples, minimal use of expensive reagents, testing of multiple samples in parallel, and point-of-care testing, all of which increase throughput and reduce...

  5. The national cancer institute (NCI) and cancer biology in a 'post genome world'

    International Nuclear Information System (INIS)

    The National Cancer Institute (NCI) exists to reduce the burden of all cancers through research and discovery. Extensive restructuring of the NCI over the past year has been aimed at assuring that the institution functions in all ways to promote opportunities for discovery in the laboratory, in the clinic, and in the community. To do this well requires the difficult and almost paradoxical problem of planning for scientific discovery which, in turn is based on the freedom to pursue the unanticipated. The intellectual and structural landscape of science is changing and it places new challenges, new demands and new opportunities for facilitating discovery. The nature of cancer as a disease of genomic instability and of accumulated genetic change, coupled with a possibility of the development of new technologies for reading, utilizing, interpreting and manipulating the genome of single cells, provides unprecedented opportunities for a new type of high through-put biology that will change the nature of discovery, cancer detection, diagnosis, prognosis, therapeutic decision-making and therapeutic discovery. To capture these new opportunities will require attention to be paid to integrate the development of technology and new scientific discoveries with the ability to apply advances rapidly and efficiently through clinical trials

  6. Shared signaling pathways in normal and breast cancer stem cells

    Directory of Open Access Journals (Sweden)

    Gautam K Malhotra

    2011-01-01

    Full Text Available Recent advances in our understanding of breast cancer biology have led to the identification of a subpopulation of cells within tumors that appear to be responsible for initiating and propagating the cancer. These tumor initiating cells are not only unique in their ability to generate tumors, but also share many similarities with elements of normal adult tissue stem cells, and have therefore been termed cancer stem cells (CSCs. These CSCs often inappropriately use many of the same signaling pathways utilized by their normal stem cell counterparts which may present a challenge to the development of CSC specific therapies. Here, we discuss three major stem cell signaling pathways (Notch, Wnt, and Hedgehog; with a focus on their function in normal mammary gland development and their misuse in breast cancer stem cell fate determination.

  7. Recursive Partitioning Analysis of Mediastinal N2 Lymph Node Involvement with Selected Biological Markers in Operable Non-small Cell Lung Cancer: A Correlative Study

    Directory of Open Access Journals (Sweden)

    Hakan Bozcuk

    2007-01-01

    Full Text Available Background: Expressions of various biomarkers in non-small cell lung cancer (NSCLC have been linked with the prognosis and involvement of mediastinal lymph nodes.Methods: In this study, we utilized recursive partitioning analysis (RPA by using P53, c-erb-B2, and P-glycoprotein (PGP expressions evaluated by immunohistochemistry to estimate retrospectively the likelihood of the occult N2 mediastinal lymph node involvement in patients with operable NSCLC.Results: In univariate tests, immunohistochemical staining of the primary tumor for these 3 markers in 61 patients undergoing surgery revealed no direct relationship with the N2 involvement. However, RPA demonstrated in patients aged 75 and with 4 mediastinal lymph nodes removed that, high PGP expression frequency (20% predicted an increased likelihood of the N2 involvement (46.7%, R2 = 0.25. Univariate nominal logistic regression analysis revealed that RPA group affiliation, and the number of mediastinal lymph nodes resected (logarithmic transformation were associated with the metastasis to N2 lymph nodes (χ2 = 17.59, p = 0.0005, and χ2 = 2.40, p = 0.0654, respectively. Multivariate analysis confirmed that only RPA group affiliation predicted the N2 involvement (χ2 = 14.63, p = 0.0022.Conclusion: This study shows for the first time that PGP expression of the primary tumor may help to predict the occult N2 mediastinal lymph node involvement in NSCLC. Thus, further research is required to understand whether PGP expression may aid in the decision process for preoperative mediastinoscopy.

  8. The biology of hematopoietic stem cells.

    Science.gov (United States)

    Szilvassy, Stephen J

    2003-01-01

    Rarely has so much interest from the lay public, government, biotechnology industry, and special interest groups been focused on the biology and clinical applications of a single type of human cell as is today on stem cells, the founder cells that sustain many, if not all, tissues and organs in the body. Granting organizations have increasingly targeted stem cells as high priority for funding, and it appears clear that the evolving field of tissue engineering and regenerative medicine will require as its underpinning a thorough understanding of the molecular regulation of stem cell proliferation, differentiation, self-renewal, and aging. Despite evidence suggesting that embryonic stem (ES) cells might represent a more potent regenerative reservoir than stem cells collected from adult tissues, ethical considerations have redirected attention upon primitive cells residing in the bone marrow, blood, brain, liver, muscle, and skin, from where they can be harvested with relative sociological impunity. Among these, it is arguably the stem and progenitor cells of the mammalian hematopoietic system that we know most about today, and their intense study in rodents and humans over the past 50 years has culminated in the identification of phenotypic and molecular genetic markers of lineage commitment and the development of functional assays that facilitate their quantitation and prospective isolation. This review focuses exclusively on the biology of hematopoietic stem cells (HSCs) and their immediate progeny. Nevertheless, many of the concepts established from their study can be considered fundamental tenets of an evolving stem cell paradigm applicable to many regenerating cellular systems. PMID:14734085

  9. Stem cells in human breast cancer

    OpenAIRE

    Roberto Oliveira, Lucinei; Jeffrey, Stefanie S; Ribeiro Silva, Alfredo

    2010-01-01

    Increasing data support cancer as a stem cell-based disease. Cancer stem cells (CSCs) have beenfound in different human cancers, and recent evidenceindicates that breast cancer originates from and ismaintained by its own CSCs, as well as the normalmammary gland. Mammary stem cells and breast CSCshave been identified and purified in in vitroculturesystems, transplantation assays and/or by cell surfaceantigen identification. Cell surface markers enable thefunctional isolation of stem cells that...

  10. Tamoxifen-resistant breast cancer cells possess cancer stem-like cell properties

    Institute of Scientific and Technical Information of China (English)

    LIU Hui; ZHANG Heng-wei; SUN Xian-fu; GUO Xu-hui; HE Ya-ning; CUI Shu-de; FAN Qing-xia

    2013-01-01

    Background Cancer stem cells (CSCs) are the cause of cancer recurrence because they are resistant to conventional therapy and contribute to cancer growth and metastasis.Endocrinotherapy is the most common breast cancer therapy and acquired tamoxifen (TAM) resistance is the main reason for endocrinotherapy failure during such therapy.Although acquired resistance to endocrine treatment has been extensively studied,the underlying mechanisms are unclear.We hypothesized that breast CSCs played an important role in TAM-induced resistance during breast cancer therapy.Therefore,we investigated the biological characteristics of TAM-resistant (TAM-R) breast cancer cells.Methods Mammosphere formation and tumorigenicity of wild-type (WT) and TAM-R MCF7 cells were tested by a mammosphere assay and mouse tumor xenografts respectively.Stem-cell markers (SOX-2,OCT-4,and CD133) and epithelial-mesenchymal transition (EMT) markers were tested by quantitative real-time (qRT)-PCR.Morphological observation was performed to characterize EMT.Results After induction of TAM resistance,TAM-R MCF7 cells exhibited increased proliferation in the presence of TAM compared to that of WT MCF7 cells (P <0.05),indicating enhanced TAM resistance of TAM-R MCF7 cells compared to that of WT MCF7 cells.TAM-R MCF7 cells showed enhanced mammosphere formation and tumorigenicity in nude mice compared to that of WT MCF7 cells (P <0.01),demonstrating the elevated CSC properties of TAM-R MCF7 cells.Consistently,qRT-PCR revealed that TAM-R MCF7 cells expressed increased mRNA levels of stem cell markers including SOX-2,OCT-4,and CD133,compared to those of WT MCF7 cells (P <0.05).Morphologically,TAM-R MCF7 cells showed a fibroblastic phenotype,but WT MCF7 cells were epithelial-like.After induction of TAM resistance,qRT-PCR indicated that MCF7 cells expressed increased mRNA levels of Snail,vimentin,and N-cadherin and decreased levels of E-cadherin,which are considered as EMT characteristics (P <0

  11. New insights into pancreatic cancer stem cells

    Institute of Scientific and Technical Information of China (English)

    Chinthalapally V Rao; Altaf Mohammed

    2015-01-01

    Pancreatic cancer (PC) has been one of the deadliest of allcancers, with almost uniform lethality despite aggressivetreatment. Recently, there have been important advancesin the molecular, pathological and biological understandingof pancreatic cancer. Even after the emergence of recentnew targeted agents and the use of multiple therapeuticcombinations, no treatment option is viable in patients withadvanced cancer. Developing novel strategies to targetprogression of PC is of intense interest. A small populationof pancreatic cancer stem cells (CSCs) has been foundto be resistant to chemotherapy and radiation therapy.CSCs are believed to be responsible for tumor initiation,progression and metastasis. The CSC research has recentlyachieved much progress in a variety of solid tumors,including pancreatic cancer to some extent. This leads tofocus on understanding the role of pancreatic CSCs. Thefocus on CSCs may offer new targets for prevention andtreatment of this deadly cancer. We review the most salientdevelopments in important areas of pancreatic CSCs. Here,we provide a review of current updates and new insightson the role of CSCs in pancreatic tumor progression withspecial emphasis on DclK1 and Lgr5, signaling pathwaysaltered by CSCs, and the role of CSCs in prevention andtreatment of PC.

  12. Cancer stem cell markers in common cancers - therapeutic implications

    DEFF Research Database (Denmark)

    Klonisch, Thomas; Wiechec, Emilia; Hombach-Klonisch, Sabine;

    2008-01-01

    Rapid advance in the cancer stem cell field warrants optimism for the development of more reliable cancer therapies within the next 2-3 decades. Below, we characterize and compare the specific markers that are present on stem cells, cancer cells and cancer stem cells (CSC) in selected tissues......, the last part of the review discusses future directions of this intriguing new research field in the context of new diagnostic and therapeutic opportunities....

  13. Metformin kills and radiosensitizes cancer cells and preferentially kills cancer stem cells

    OpenAIRE

    Chang W. Song; Hyemi Lee; Dings, Ruud P. M.; Brent Williams; John Powers; Troy Dos Santos; Bo-Hwa Choi; Heon Joo Park

    2012-01-01

    The anti-cancer effects of metformin, the most widely used drug for type 2 diabetes, alone or in combination with ionizing radiation were studied with MCF-7 human breast cancer cells and FSaII mouse fibrosarcoma cells. Clinically achievable concentrations of metformin caused significant clonogenic death in cancer cells. Importantly, metformin was preferentially cytotoxic to cancer stem cells relative to non-cancer stem cells. Metformin increased the radiosensitivity of cancer cells in vitro, ...

  14. Technologies for deriving primary tumor cells for use in personalized cancer therapy

    OpenAIRE

    Mitra, Abhisek; Mishra, Lopa; Li, Shulin

    2013-01-01

    For decades, immortal cancer cell lines have constituted an accessible, easily usable set of biological models to investigate cancer biology and explore the potential efficacy of anticancer drugs. However, numerous studies suggest that these cell lines poorly represent the diversity, heterogeneity and drug-resistant tumors occurring in patients. The derivation and short -term culture of primary cells from solid tumors have thus gained significant importance in personalized cancer therapy. Thi...

  15. Cancer Theory from Systems Biology Point of View

    Science.gov (United States)

    Wang, Gaowei; Tang, Ying; Yuan, Ruoshi; Ao, Ping

    In our previous work, we have proposed a novel cancer theory, endogenous network theory, to understand mechanism underlying cancer genesis and development. Recently, we apply this theory to hepatocellular carcinoma (HCC). A core endogenous network of hepatocyte was established by integrating the current understanding of hepatocyte at molecular level. Quantitative description of the endogenous network consisted of a set of stochastic differential equations which could generate many local attractors with obvious or non-obvious biological functions. By comparing with clinical observation and experimental data, the results showed that two robust attractors from the model reproduced the main known features of normal hepatocyte and cancerous hepatocyte respectively at both modular and molecular level. In light of our theory, the genesis and progression of cancer is viewed as transition from normal attractor to HCC attractor. A set of new insights on understanding cancer genesis and progression, and on strategies for cancer prevention, cure, and care were provided.

  16. A mathematical model of cancer cells with phenotypic plasticity

    Directory of Open Access Journals (Sweden)

    Da Zhou

    2015-08-01

    Full Text Available Purpose: The phenotypic plasticity of cancer cells is recently becoming a cutting-edge research area in cancer, which challenges the cellular hierarchy proposed by the conventional cancer stem cell theory. In this study, we establish a mathematical model for describing the phenotypic plasticity of cancer cells, based on which we try to find some salient features that can characterize the dynamic behavior of the phenotypic plasticity especially in comparison to the hierarchical model of cancer cells. Methods: We model cancer as population dynamics composed of different phenotypes of cancer cells. In this model, not only can cancer cells divide (symmetrically and asymmetrically and die, but they can also convert into other cellular phenotypes. According to the Law of Mass Action, the cellular processes can be captured by a system of ordinary differential equations (ODEs. On one hand, we can analyze the long-term stability of the model by applying qualitative method of ODEs. On the other hand, we are also concerned about the short-term behavior of the model by studying its transient dynamics. Meanwhile, we validate our model to the cell-state dynamics in published experimental data.Results: Our results show that the phenotypic plasticity plays important roles in both stabilizing the distribution of different phenotypic mixture and maintaining the cancer stem cells proportion. In particular, the phenotypic plasticity model shows decided advantages over the hierarchical model in predicting the phenotypic equilibrium and cancer stem cells’ overshoot reported in previous biological experiments in cancer cell lines.Conclusion: Since the validity of the phenotypic plasticity paradigm and the conventional cancer stem cell theory is still debated in experimental biology, it is worthy of theoretically searching for good indicators to distinguish the two models through quantitative methods. According to our study, the phenotypic equilibrium and overshoot

  17. Culturing intestinal stem cells: applications for colorectal cancer research

    OpenAIRE

    Fujii, Masayuki; Sato, Toshiro

    2014-01-01

    Recent advance of sequencing technology has revealed genetic alterations in colorectal cancer (CRC). The biological function of recurrently mutated genes has been intensively investigated through mouse genetic models and CRC cell lines. Although these experimental models may not fully reflect biological traits of human intestinal epithelium, they provided insights into the understanding of intestinal stem cell self-renewal, leading to the development of novel human intestinal organoid culture...

  18. Countercurrent distribution of biological cells

    Science.gov (United States)

    1982-01-01

    It is known that the addition of phosphate buffer to two polymer aqueous phase systems has a strong effect on the partition behavior of cells and other particles in such mixtures. The addition of sodium phosphate to aqueous poly(ethylene glycol) dextran phase systems causes a concentration-dependent shift in binodial on the phase diagram, progressively lowering the critical conditions for phase separation as the phosphate concentration is increased. Sodium chloride produces no significant shift in the critical point relative to the salt-free case. Accurate determinations of the phase diagram require measurements of the density of the phases; data is presented which allows this parameter to be calculated from polarimetric measurements of the dextran concentrations of both phases. Increasing polymer concentrations in the phase systems produce increasing preference of the phosphate for the dextran-rich bottom phase. Equilibrium dialysis experiments showed that poly(ethylene glycol) effectively rejected phosphate, and to a lesser extent chloride, but that dextran had little effect on the distribution of either salt. Increasing ionic strength via addition of 0.15 M NaCl to phase systems containing 0.01 M phosphate produces an increased concentration of phosphate ions in the bottom dextran-rich phase, the expected effect in this type of Donnan distribution.

  19. Autotaxin: Its Role in Biology of Melanoma Cells and as a Pharmacological Target

    Directory of Open Access Journals (Sweden)

    Maciej Jankowski

    2011-01-01

    Full Text Available Autotaxin (ATX is an extracellular lysophospholipase D (lysoPLD released from normal cells and cancer cells. Activity of ATX is detected in various biological fluids. The lysophosphatidic acid (LPA is the main product of ATX. LPA acting through specific G protein-coupled receptors (LPA1-LPA6 affects immunological response, normal development, and malignant tumors' formation and progression. In this review, the impact of autotoxin on biology of melanoma cells and potential treatment is discussed.

  20. The Biology of Allogeneic Hematopoietic Cell Resistance

    Science.gov (United States)

    Shizuru, Judith A.; Bhattacharya, Deepta; Cavazzana-Calvo, Marina

    2016-01-01

    At the most basic level, success of an allogeneic hematopoietic cell transplantation (HCT) procedure relies upon the engraftment of recipients with donor hematopoietic stem cells (HSCs) that will generate blood formation for the life of that individual. The formula to achieve durable HSC engraftment involves multiple factors including the recipient conditioning regimen, the nature of the genetic disparity between donor and recipient, and the content of the hematopoietic graft. Animal and clinical studies have shown that the biology of host resistance is complex, involving both immune and nonimmune elements. In this article, we review the factors that contribute to host resistance, describe emerging concepts on the basic biology of resistance, and discuss hematopoietic resistance as it relates specifically to patients with severe combined immunodeficiencies (SCID)— disorders that bring unique insights into the dynamics of cell replacement by allogeneic HSCs and progenitor cells. PMID:19913629

  1. Niche construction game cancer cells play

    Science.gov (United States)

    Bergman, Aviv; Gligorijevic, Bojana

    2015-10-01

    Niche construction concept was originally defined in evolutionary biology as the continuous interplay between natural selection via environmental conditions and the modification of these conditions by the organism itself. Processes unraveling during cancer metastasis include construction of niches, which cancer cells use towards more efficient survival, transport into new environments and preparation of the remote sites for their arrival. Many elegant experiments were done lately illustrating, for example, the premetastatic niche construction, but there is practically no mathematical modeling done which would apply the niche construction framework. To create models useful for understanding niche construction role in cancer progression, we argue that a) genetic, b) phenotypic and c) ecological levels are to be included. While the model proposed here is phenomenological in its current form, it can be converted into a predictive outcome model via experimental measurement of the model parameters. Here we give an overview of an experimentally formulated problem in cancer metastasis and propose how niche construction framework can be utilized and broadened to model it. Other life science disciplines, such as host-parasite coevolution, may also benefit from niche construction framework adaptation, to satisfy growing need for theoretical considerations of data collected by experimental biology.

  2. Progress of transcription factor Twist expression in breast cancer and its biological effect

    Institute of Scientific and Technical Information of China (English)

    Tian Qian

    2016-01-01

    Breast cancer is the most common malignant tumor in women and the pathogenesis is not fully elucidated. Proliferation, invasion, epithelial-mesenchymal transition and angiogenesis are the links closely related to the occurrence and development of breast cancer. Twist is a type of basic helix-loop-helix transcription factor that can affect cell proliferation and invasion process, epithelial-mesenchymal transition process and angiogenesis process through regulating the transcription of downstream target genes. In the research, the study of transcription factor Twist expression in breast cancer and its biological effect is reviewed.

  3. Targeted therapy in non-small cell lung cancer

    Institute of Scientific and Technical Information of China (English)

    Shou-Ching Tang

    2004-01-01

    @@ 1 Introduction Recent progress in molecular biology has enabled us to better understand the molecular mechanism underlying pathogenesis of human malignancy including lung cancer. Sequencing of human genome has identified many oncogenes and tumor suppressor genes,giving us a better understanding of the molecular events leading to the formation, progression, metastasis, and the development of drug resistance in human lung cancer. In addition, many signal transduction pathways have been discovered that play important roles in lung cancer. Novel strategy of anti-cancer drug development now involves the identification and development of targeted therapy that interrupts one or more than one pathways or cross-talk among different signal transduction pathways. In addition, efforts are underway that combine the traditional cytotoxic (non-targeted) agents with the biological (targeted) therapy to increase the response rate and survival in patients with lung cancer, especially advanced non-small cell lung cancer (NSCLC).

  4. Biological cell as IR-optical resonator

    Czech Academy of Sciences Publication Activity Database

    Cifra, Michal

    Recife : OSA, 2011, TuA2. ISBN 978-1-55752-903-9. ISSN 2162-2701. [Latin America Optics and Photonics Conference, LAOP 2010. Recife (BR), 27.09.2010-30.09.2010] R&D Projects: GA ČR GPP102/10/P454 Institutional research plan: CEZ:AV0Z20670512 Keywords : Biological cells * Eigen modes * Living cell Subject RIV: JA - Electronics ; Optoelectronics, Electrical Engineering

  5. Towards systems thinking in cell biology education

    OpenAIRE

    Verhoeff, Roald Pieter

    2003-01-01

    Students are taught a large variety of life structures and processes at the cellular level. The concepts used to describe them are mainly drawn from the sub-cellular level, but this knowledge seems to be fragmentary if its integration at the cellular and organismic level remains undone. As a consequence, many students fail to acquire coherent conceptual understanding of the cell as a basic and functional unit of the organism. To enhance the coherence in students’ cell biological knowledge we ...

  6. Evaluation of treatment response for breast cancer: are we entering the era of "biological complete remission"?

    Institute of Scientific and Technical Information of China (English)

    Li Bian; Tao Wang; Yi Liu; Hui-Qiang Zhang; Jin-Jie Song; Shao-Hua Zhang; Shi-Kai Wu; San-Tai Song; Ze-Fei Jiang

    2012-01-01

    Breast cancer is one of the most common malignancies in women.The post-operative recurrence and metastasis are the leading causes of breast cancer-related mortality.In this study,we tried to explore the role of circulating tumor cell (CTC) detection combination PET/CT technology evaluating the prognosis and treatment response of patients with breast cancer; meanwhile,we attempted to assess the concept of "biological complete remission" (bCR) in this regard.A 56-year-old patient with breast cancer (T2N1M1,stage Ⅳ left breast cancer,with metastasis to axillary lymph nodes and lungs) received 6 cycles of salvage treatment with albumin-bound paclitaxel plus capecitabine and trastuzumab.Then,she underwent CTC detection and PET/CT for efficacy evaluation.CTC detection combination PET/CT is useful for the evaluation of the biological efficacy of therapies for breast cancer.The bCR of the patient appeared earlier than the conventional clinical imaging complete remission and promised the histological (pathological) complete remission.The integrated application of the concepts including bCR,imageological CR,and histological CR can achieve the early and accurate assessment of biological therapeutic reponse and prognosis of breast cancer.

  7. Biology of Human Papillomavirus–Related Oropharyngeal Cancer

    OpenAIRE

    Howard, Jason D.; Chung, Christine H.

    2012-01-01

    Recent data show that human papillomavirus–positive oropharyngeal cancer (OPC) has a distinct biological and clinical behavior compared with human papillomavirus–negative OPC. As this subset of head and neck cancer represents an increasing public health concern, a thorough understanding of the causative and mechanistic differences between these diseases and how these distinctions impact clinical treatment is required. In this review, we will summarize recent data in epidemiology, the mechanis...

  8. Cancer: A Problem of Developmental Biology; Scientific Evidence for Reprogramming and Differentiation Therapy.

    Science.gov (United States)

    Sell, Stewart; Nicolini, Andrea; Ferrari, Paola; Biava, Pier M

    2016-01-01

    Current medical literature acknowledges that embryonic micro-environment is able to suppress tumor development. Administering carcinogenic substances during organogenesis in fact leads to embryonic malformations, but not to offspring tumor growth. Once organogenesis has ended, administration of carcinogenic substances causes a rise in offspring tumor development. These data indicate that cancer can be considered a deviation in normal development, which can be regulated by factors of the embryonic microenvironment. Furthermore, it has been demonstrated that teratoma differentiates into normal tissues once it is implanted in the embryo. Recently, it has been shown that implanting a melanoma in Zebrafish embryo did not result in a tumor development; however, it did in the adult specimen. This demonstrates that cancer cells can differentiate into normal tissues when implanted in the embryo. In addition, it was demonstrated that other tumors can revert into a normal phenotype and/or differentiate into normal tissue when implanted in the embryo. These studies led some authors to define cancer as a problem of developmental biology and to predict the present concept of "cancer stem cells theory". In this review, we record the most important researches about the reprogramming and differentiation treatments of cancer cells to better clarify how the substances taken from developing embryo or other biological substances can induce differentiation of malignant cells. Lastly, a model of cancer has been proposed here, conceived by one of us, which is consistent with the reality, as demonstrated by a great number of researches. This model integrates the theory of the "maturation arrest" of cancer cells as conceived by B. Pierce with the theory which describes cancer as a process of deterministic chaos determined by genetic and/or epigenetic alterations in differentiated cells, which leads a normal cell to become cancerous. All the researches here described demonstrated that cancer

  9. Natural killer cells: Biology, functions and clinical relevance

    Directory of Open Access Journals (Sweden)

    Vojvodić Svetlana

    2010-01-01

    Full Text Available Introduction. Natural Killer cells (NK cells represent the subset of peripheral lymphocytes that play critical role in the innate immune response to virus-infected and tumor transformed cells. Lysis of NK sensitive target cells could be mediated independently of antigen stimulation and without requirement of peptide presentation by the major histocompatibility complex (MHC molecules. NK cell activity and functions are controlled by a considerable number of cell surface receptors, which exist in both inhibitory and activating isoforms. There are several groups of NK cell surface receptors: 1 killer immunoglobulin like receptors-KIR, 2 C-type lectin receptors,3natural citotoxicity receptors-NCR and 4 Toll-like receptors-TLR. Functions of NK receptors. Defining the biology of NK cell surface receptors has contributed to the concept of the manner how NK cells selectively recognize and lyse tumor and virally infected cells while sparing normal cells. Further, identification of NK receptor ligands and their expression on the normal and transformed cells has led to the development of clinical approaches to manipulating receptor/ligand interactions that showed clinical benefit. NK cells are the first lymphocyte subset that reconstitute the peripheral blood following allogeneic HSCT and multiple roles for alloreactive donor NK cells have been demonstrated, in diminishing Graft vs. Host Disease (GvHD through selective killing recipient dendritic cells, prevention of graft rejection by killing recipient T cells and participation in Graft vs. Leukaemia (GvL effect through destruction of residual host tumor cells. Conclusion. Besides their role in HSCT, NK cell receptors have an important clinical relevance that reflects from the fact that they play a crucial role in the development of some diseases as well as in possibilities of managing all NK receptors through selective expansion and usage of NK cells in cancer immunotherapy.

  10. Molecular biology of breast cancer metastasis: Clinical implications of experimental studies on metastatic inefficiency

    International Nuclear Information System (INIS)

    Recent technological advances have led to an increasing ability to detect isolated tumour cells and groups of tumour cells in patients' blood, lymph nodes or bone marrow. However, the clinical significance of these cells is unclear. Should they be considered as evidence of metastasis, necessitating aggressive treatment, or are they in some cases unrelated to clinical outcome? Quantitative experimental studies on the basic biology of metastatic inefficiency are providing clues that may help in understanding the significance of these cells. This understanding will be of use in guiding clinical studies to assess the significance of isolated tumour cells and micrometastases in cancer patients

  11. Computational Systems Biology in Cancer: Modeling Methods and Applications

    OpenAIRE

    Wayne Materi; Wishart, David S.

    2007-01-01

    In recent years it has become clear that carcinogenesis is a complex process, both at the molecular and cellular levels. Understanding the origins, growth and spread of cancer, therefore requires an integrated or system-wide approach. Computational systems biology is an emerging sub-discipline in systems biology that utilizes the wealth of data from genomic, proteomic and metabolomic studies to build computer simulations of intra and intercellular processes. Several useful descriptive and pre...

  12. Multiscale approach predictions for biological outcomes in ion-beam cancer therapy

    OpenAIRE

    Alexey Verkhovtsev; Eugene Surdutovich; Solov’yov, Andrey V.

    2016-01-01

    Ion-beam therapy provides advances in cancer treatment, offering the possibility of excellent dose localization and thus maximising cell-killing within the tumour. The full potential of such therapy can only be realised if the fundamental mechanisms leading to lethal cell damage under ion irradiation are well understood. The key question is whether it is possible to quantitatively predict macroscopic biological effects caused by ion radiation on the basis of physical and chemical effects rela...

  13. Cancer Systems Biology: a peak into the future of patient care?

    OpenAIRE

    Werner, Henrica M. J.; Mills, Gordon B.; Ram, Prahlad T.

    2014-01-01

    Traditionally, scientific research has focused on studying individual events, such as single mutations, gene function or the effect of the manipulation of one protein on a biological phenotype. A range of technologies, combined with the ability to develop robust and predictive mathematical models, is beginning to provide information that will enable a holistic view of how the genomic and epigenetic aberrations in cancer cells can alter the homeostasis of signalling networks within these cells...

  14. Advances in radiation biology: Radiosensitization in DNA and living cells

    Science.gov (United States)

    Lacombe, S.; Sech, C. Le

    2009-06-01

    One fundamental goal of radiation biology is the evolution of concepts and methods for the elaboration of new approaches and protocols for the treatment of cancers. In this context, the use of fast ions as ionizing particles offers the advantage of optimizing cell killing inside the tumor whilst preserving the surrounding healthy tissues. One extremely promising strategy investigated recently is the addition of radiosensitizers in the targeted tissue. The optimization of radiotherapy with fast ions implies a multidisciplinary approach to ionizing radiation effects on complex living systems, ranging from studies on single molecules to investigations of entire organisms. In this article we review recent studies on ion induced damages in simple and complex biological systems, from DNA to living cells. The specific aspect of radiosensitization induced by metallic atoms is described. As a fundamental result, the addition of sensitizing compounds with ion irradiation may improve therapeutic index in cancer therapy. In conclusion, new perspectives are proposed based on the experience and contribution of different communities including Surface Sciences, to improve the development of radiation biology.

  15. Discovery of the cancer stem cell related determinants of radioresistance

    International Nuclear Information System (INIS)

    Tumors are known to be heterogeneous containing a dynamic mixture of phenotypically and functionally different tumor cells. The two concepts attempting to explain the origin of intratumor heterogeneity are the cancer stem cell hypothesis and the clonal evolution model. The stochastic model argues that tumors are biologically homogenous and all cancer cells within the tumor have equal ability to propagate the tumor growth depending on continuing mutations and selective pressure. By contrast, the stem cells model suggests that cancer heterogeneity is due to the hierarchy that originates from a small population of cancer stem cells (CSCs) which are biologically distinct from the bulk tumor and possesses self-renewal, tumorigenic and multilineage potential. Although these two hypotheses have been discussed for a long time as mutually exclusive explanations of tumor heterogeneity, they are easily reconciled serving as a driving force of cancer evolution and diversity. Recent discovery of the cancer cell plasticity and heterogeneity makes the CSC population a moving target that could be hard to track and eradicate. Understanding the signaling mechanisms regulating CSCs during the course of cancer treatment can be indispensable for the optimization of current treatment strategies

  16. An electrostatic model for biological cell division

    CERN Document Server

    Faraggi, Eshel

    2010-01-01

    Probably the most fundamental processes for biological systems is their ability to create themselves through the use of cell division and cell differentiation. In this work a simple physical model is proposed for biological cell division. The model consists of a positive ionic gradient across the cell membrane, and concentration of charge at the nodes of the spindle and on the chromosomes. A simple calculation, based on Coulomb's Law, shows that under such circumstances a chromosome will tend to break up to its constituent chromatids and that the chromatids will be separated by a distance that is an order of thirty percent of the distance between the spindle nodes. Further repulsion between the nodes will tend to stretch the cell and eventually break the cell membrane between the separated chromatids, leading to cell division. The importance of this work is in continuing the understanding of the electromagnetic basis of cell division and providing it with an analytical model. A central implication of this and...

  17. Nanomechanical analysis of cells from cancer patients

    Science.gov (United States)

    Cross, Sarah E.; Jin, Yu-Sheng; Rao, Jianyu; Gimzewski, James K.

    2007-12-01

    Change in cell stiffness is a new characteristic of cancer cells that affects the way they spread. Despite several studies on architectural changes in cultured cell lines, no ex vivo mechanical analyses of cancer cells obtained from patients have been reported. Using atomic force microscopy, we report the stiffness of live metastatic cancer cells taken from the body (pleural) fluids of patients with suspected lung, breast and pancreas cancer. Within the same sample, we find that the cell stiffness of metastatic cancer cells is more than 70% softer, with a standard deviation over five times narrower, than the benign cells that line the body cavity. Different cancer types were found to display a common stiffness. Our work shows that mechanical analysis can distinguish cancerous cells from normal ones even when they show similar shapes. These results show that nanomechanical analysis correlates well with immunohistochemical testing currently used for detecting cancer.

  18. Mesenchymal Stem/Stromal Cells in Stromal Evolution and Cancer Progression

    OpenAIRE

    Francesca Cammarota; Laukkanen, Mikko O

    2016-01-01

    The study of cancer biology has mainly focused on malignant epithelial cancer cells, although tumors also contain a stromal compartment, which is composed of stem cells, tumor-associated fibroblasts (TAFs), endothelial cells, immune cells, adipocytes, cytokines, and various types of macromolecules comprising the extracellular matrix (ECM). The tumor stroma develops gradually in response to the needs of epithelial cancer cells during malignant progression initiating from increased local vascul...

  19. Telomerase and telomeres : From basic biology to cancer treatment

    NARCIS (Netherlands)

    Helder, MN; Wisman, GBA; van der Zee, AGJ

    2002-01-01

    The limited capacity to divide is one of the major differences between normal somatic cells and cancerous cells. This finite life span' of somatic cells is closely linked to loss of telomeric DNA at telomeres, the 'chromosome caps' consisting of repeated (TTAGGG) sequences. In more than 85% of advan

  20. Electron Tomography in Plant Cell Biology

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    This review focuses on the contribution of electron tomography-based techniques to our understanding of cellular processes in plant cells. Electron microscopy techniques have evolved to provide better three-dimensional resolution and improved preservation of the subcellular components. In particular, the combination of cryofixation/freeze substitution and electron tomography have allowed plant cell biologists to image organelles and macromolecular complexes in their native cellular context with unprecedented three-dimensional resolution (4-7 nm). Until now, electron tomography has been applied in plant cell biology for the study of cytokinesis, Golgi structure and trafficking, formation of plant endosome/prevacuolar compartments, and organization of photosynthetic membranes. We discuss in this review the new insights that these tomographic studies have brought to the plant biology field.

  1. Measuring density and compressibility of white blood cells and prostate cancer cells by microchannel acoustophoresis

    DEFF Research Database (Denmark)

    Barnkob, Rune; Augustsson, Per; Magnusson, Cecilia; Lilja, Hans; Laurell, Thomas; Bruus, Henrik

    determine the density and compressibility of individual cells enables the prediction and alteration of the separation outcome for a given cell mixture. We apply the method on white blood cells (WBCs) and DU145 prostate cancer cells (DUCs) aiming to improve isolation of circulating tumor cells from blood, an......We present a novel method for the determination of density and compressibility of individual particles and cells undergoing microchannel acoustophoresis in an arbitrary 2D acoustic field. Our method is a critical advancement within acoustophoretic separation of biological cells, as the ability to...... emerging tool in the monitoring and characterizing of metastatic cancer....

  2. Role of cancer stem cells in hepatocarcinogenesis

    OpenAIRE

    Wang, Bo; Jacob, Samson T.

    2011-01-01

    There has been considerable interest in cancer stem cells (CSCs) among cancer biologists and clinicians, most likely because of their role in the heterogeneity of cancer and their potential application in cancer therapeutics. Recent studies suggest that CSCs play a key role in liver carcinogenesis. A small subpopulation of cancer cells with CSC properties has been identified and characterized from hepatocellular carcinoma (HCC) cell lines, animal models and human primary HCCs. Considering the...

  3. Neuroendocrine differentiation of prostate cancer cells

    Czech Academy of Sciences Publication Activity Database

    Souček, Karel; Pernicová, Zuzana; Lincová, Eva; Staršíchová, Andrea; Kozubík, Alois

    2008-01-01

    Roč. 102, č. 5 (2008), s. 393. ISSN 0009-2770. [Mezioborové setkání mladých biologů, biochemiků a chemiků. Konference Sigma-Aldrich /8./. 10.06.2008-13.06.2008, Devět skal - Žďárské vrchy] R&D Projects: GA ČR(CZ) GA204/07/0834; GA ČR(CZ) GA310/07/0961 Institutional research plan: CEZ:AV0Z50040507; CEZ:AV0Z50040702 Keywords : neuroendocrine differentiation * prostate cancer * neuroendocrine-like cells Subject RIV: BO - Biophysics

  4. HMGCR is up-regulated in gastric cancer and promotes the growth and migration of the cancer cells.

    Science.gov (United States)

    Chushi, Li; Wei, Wu; Kangkang, Xie; Yongzeng, Feng; Ning, Xie; Xiaolei, Chen

    2016-08-01

    Alteration of metabolic profile is one of the hallmarks of cancer cells. Statin, the inhibitors for synthesis of cholesterol, has shown anti-cancer effects on the gastric cancer cells. However, the functions of its target, HMGCR, in the progression of gastric cancer remain unknown. In the present study, we investigated the expression profile and the biological functions of HMGCR in gastric cancer. It was found that the expression of HMGCR was increased in gastric cancer tissues. Over-expression of HMGCR promoted the growth and migration of gastric cancer cells, while knocking down the expression of HMGCR inhibited the growth, migration and tumorigenesis of gastric cancer cells. In the further molecular mechanism study, HMGCR was shown to activate Hedgehog/Gli1 signaling and promoted the expression of Gli1 target genes. Taken together, this study demonstrated the tumor-promoting effects of HMGCR in gastric cancer and suggested HMGCR as a promising therapeutic target. PMID:27085483

  5. Do Cell Phones Cause Cancer?

    CERN Document Server

    Leikind, Bernard

    2010-01-01

    Do cell phones, household electrical power wiring or appliance, or high voltage power lines cause cancer? Fuggedaboudit! No way! When pigs fly! When I'm the Pope! Don't text while you're driving, however, or eat your cell phone. All organisms absorb microwave radiation directly as thermal energy. In living organisms, the organisms' thermal control systems, including the blood flow, and various cooling mechanisms, such as sweating in humans, that work to maintain a stable body temperature rapidly transfer the absorbed energy to the environment. Any temperature rise is small or even unobserved. Any proposed mechanism by which cell phone radiation might cause cancer must begin with this fact. But the amount of radiation absorbed from a cell phone is less than that produced by normal metabolic processes, and much less than that produced by, for example, exercise. None of these normal metabolic processes cause cancer. Therefore, the much smaller amounts of energy from cell phones doesn't cause cancer either. All f...

  6. Ganoderma lucidum (Reishi) inhibits cancer cell growth and expression of key molecules in inflammatory breast cancer.

    Science.gov (United States)

    Martínez-Montemayor, Michelle M; Acevedo, Raysa Rosario; Otero-Franqui, Elisa; Cubano, Luis A; Dharmawardhane, Suranganie F

    2011-01-01

    Inflammatory breast cancer (IBC) is the most lethal and least understood form of advanced breast cancer. Its lethality originates from its nature of invading the lymphatic system and absence of a palpable tumor mass. Different from other metastatic breast cancer cells, IBC cells invade by forming tumor spheroids that retain E-cadherin-based cell-cell adhesions. Herein we describe the potential of the medicinal mushroom Ganoderma lucidum (Reishi) as an attractive candidate for anti-IBC therapy. Reishi contains biological compounds that are cytotoxic against cancer cells. We report the effects of Reishi on viability, apoptosis, invasion, and its mechanism of action in IBC cells (SUM-149). Results show that Reishi selectively inhibits cancer cell viability although it does not affect the viability of noncancerous mammary epithelial cells. Apoptosis induction is consistent with decreased cell viability. Reishi inhibits cell invasion and disrupts the cell spheroids that are characteristic of the IBC invasive pathology. Reishi decreases the expression of genes involved in cancer cell survival and proliferation (BCL-2, TERT, PDGFB), and invasion and metastasis (MMP-9), whereas it increases the expression of IL8. Reishi reduces BCL-2, BCL-XL, E-cadherin, eIF4G, p120-catenin, and c-Myc protein expression and gelatinase activity. These findings suggest that Reishi is an effective anti-IBC therapeutic. PMID:21888505

  7. Cellular transfer and AFM imaging of cancer cells using Bioimprint

    Directory of Open Access Journals (Sweden)

    Melville DOS

    2006-01-01

    Full Text Available Abstract A technique for permanently capturing a replica impression of biological cells has been developed to facilitate analysis using nanometer resolution imaging tools, namely the atomic force microscope (AFM. The method, termed Bioimprint™, creates a permanent cell 'footprint' in a non-biohazardous Poly (dimethylsiloxane (PDMS polymer composite. The transfer of nanometer scale biological information is presented as an alternative imaging technique at a resolution beyond that of optical microscopy. By transferring cell topology into a rigid medium more suited for AFM imaging, many of the limitations associated with scanning of biological specimens can be overcome. Potential for this technique is demonstrated by analyzing Bioimprint™ replicas created from human endometrial cancer cells. The high resolution transfer of this process is further detailed by imaging membrane morphological structures consistent with exocytosis. The integration of soft lithography to replicate biological materials presents an enhanced method for the study of biological systems at the nanoscale.

  8. Renal cell cancer among African Americans: an epidemiologic review

    Directory of Open Access Journals (Sweden)

    Lipworth Loren

    2011-04-01

    Full Text Available Abstract Incidence rates for renal cell cancer, which accounts for 85% of kidney cancers, have been rising more rapidly among blacks than whites, almost entirely accounted for by an excess of localized disease. This excess dates back to the 1970s, despite less access among blacks to imaging procedures in the past. In contrast, mortality rates for this cancer have been virtually identical among blacks and whites since the early 1990s, despite the fact that nephrectomy rates, regardless of stage, are lower among blacks than among whites. These observations suggest that renal cell cancer may be a less aggressive tumor in blacks. We have reviewed the epidemiology of renal cell cancer, with emphasis on factors which may potentially play a role in the observed differences in incidence and mortality patterns of renal cell cancer among blacks and whites. To date, the factors most consistently, albeit modestly, associated with increased renal cell cancer risk in epidemiologic studies among whites - obesity, hypertension, cigarette smoking - likely account for less than half of these cancers, and there is virtually no epidemiologic evidence in the literature pertaining to their association with renal cell cancer among blacks. There is a long overdue need for detailed etiologic cohort and case-control studies of renal cell cancer among blacks, as they now represent the population at highest risk in the United States. In particular, investigation of the influence on renal cell cancer development of hypertension and chronic kidney disease, both of which occur substantially more frequently among blacks, is warranted, as well as investigations into the biology and natural history of this cancer among blacks.

  9. Integration of proteomics into systems biology of cancer

    OpenAIRE

    Hanash, S; Schliekelman, M.; Q. Zhang; Taguchi, A

    2012-01-01

    Deciphering the complexity and heterogeneity of cancer benefits from integration of proteomic level data into systems biology efforts. The opportunities available as a result of advances in proteomic technologies, the successes to date and the challenges involved in integrating diverse datasets are addressed in this review.

  10. Treatment Option Overview (Renal Cell Cancer)

    Science.gov (United States)

    ... Genetics of Kidney Cancer Research Renal Cell Cancer Treatment (PDQ®)–Patient Version General Information About Renal Cell ... Certain factors affect prognosis (chance of recovery) and treatment options. The prognosis (chance of recovery ) and treatment ...

  11. Treatment Options for Renal Cell Cancer

    Science.gov (United States)

    ... Genetics of Kidney Cancer Research Renal Cell Cancer Treatment (PDQ®)–Patient Version General Information About Renal Cell ... Certain factors affect prognosis (chance of recovery) and treatment options. The prognosis (chance of recovery ) and treatment ...

  12. Effect of Protein Hydrolysates on Pancreatic Cancer Cells

    DEFF Research Database (Denmark)

    Ossum, Carlo G.; Andersen, Lisa Lystbæk; Nielsen, Henrik Hauch;

    Effect of Fish Protein Hydrolysates on Pancreatic Cancer Cells Carlo G. Ossum1, Lisa Lystbæk Andersen2, Henrik Hauch Nielsen2, Else K. Hoffmann1, and Flemming Jessen2 1University of Copenhagen, Department of Biology, Denmark, 2Technical University of Denmark (DTU), National Food Institute, Denmark...... activities affecting cell proliferation and ability to modulate caspase activity in pancreatic cancer cells COLO357 and BxPC-3 in vitro. A number of the hydrolysates showed caspase promoting activity; in particular products containing muscle tissue, i.e. belly flap, were able to stimulate caspase activity...... hydrolysates obtained by enzymatic hydrolysis on cancer cell proliferation. Skin and belly flap muscle from trout were hydrolysed with the unspecific proteases Alcalase, Neutrase, or UE1 (all from Novozymes, Bagsværd, Denmark) to a hydrolysis degree of 1-15%. The hydrolysates were tested for biological...

  13. Colon cancer stem cells: implications in carcinogenesis

    OpenAIRE

    Sanders, Matthew A.; Majumdar, Adhip P. N.

    2011-01-01

    The cancer stem cell model was described for hematologic malignancies in 1997 and since then evidence has emerged to support it for many solid tumors as well, including colon cancer. This model proposes that certain cells within the tumor mass are pluripotent and capable of self-renewal and have an enhanced ability to initiate distant metastasis. The cancer stem cell model has important implications for cancer treatment, since most current therapies target actively proliferating cells and may...

  14. Brain Cancer Stem Cells: Current Status on Glioblastoma Multiforme

    Directory of Open Access Journals (Sweden)

    Gilbert Bernier

    2011-03-01

    Full Text Available Glioblastoma multiforme (GBM, an aggressive brain tumor of astrocytic/neural stem cell origin, represents one of the most incurable cancers. GBM tumors are highly heterogeneous. However, most tumors contain a subpopulation of cells that display neural stem cell characteristics in vitro and that can generate a new brain tumor upon transplantation in mice. Hence, previously identified molecular pathways regulating neural stem cell biology were found to represent the cornerstone of GBM stem cell self-renewal mechanism. GBM tumors are also notorious for their resistance to radiation therapy. Notably, GBM “cancer stem cells” were also found to be responsible for this radioresistance. Herein, we will analyze the data supporting or not the cancer stem cell model in GBM, overview the current knowledge regarding GBM stem cell self-renewal and radioresistance molecular mechanisms, and discuss the potential therapeutic application of these findings.

  15. Brain Cancer Stem Cells: Current Status on Glioblastoma Multiforme

    Energy Technology Data Exchange (ETDEWEB)

    Facchino, Sabrina; Abdouh, Mohamed [Developmental Biology Laboratory, Hopital Maisonneuve-Rosemont, 5415 Boul. l' Assomption, Montreal, H1T 2M4 (Canada); Bernier, Gilbert, E-mail: gbernier.hmr@ssss.gouv.qc.ca [Developmental Biology Laboratory, Hopital Maisonneuve-Rosemont, 5415 Boul. l' Assomption, Montreal, H1T 2M4 (Canada); Faculté de Médecine, Université de Montréal, Montréal, H3T 1J4 (Canada)

    2011-03-30

    Glioblastoma multiforme (GBM), an aggressive brain tumor of astrocytic/neural stem cell origin, represents one of the most incurable cancers. GBM tumors are highly heterogeneous. However, most tumors contain a subpopulation of cells that display neural stem cell characteristics in vitro and that can generate a new brain tumor upon transplantation in mice. Hence, previously identified molecular pathways regulating neural stem cell biology were found to represent the cornerstone of GBM stem cell self-renewal mechanism. GBM tumors are also notorious for their resistance to radiation therapy. Notably, GBM “cancer stem cells” were also found to be responsible for this radioresistance. Herein, we will analyze the data supporting or not the cancer stem cell model in GBM, overview the current knowledge regarding GBM stem cell self-renewal and radioresistance molecular mechanisms, and discuss the potential therapeutic application of these findings.

  16. Brain Cancer Stem Cells: Current Status on Glioblastoma Multiforme

    International Nuclear Information System (INIS)

    Glioblastoma multiforme (GBM), an aggressive brain tumor of astrocytic/neural stem cell origin, represents one of the most incurable cancers. GBM tumors are highly heterogeneous. However, most tumors contain a subpopulation of cells that display neural stem cell characteristics in vitro and that can generate a new brain tumor upon transplantation in mice. Hence, previously identified molecular pathways regulating neural stem cell biology were found to represent the cornerstone of GBM stem cell self-renewal mechanism. GBM tumors are also notorious for their resistance to radiation therapy. Notably, GBM “cancer stem cells” were also found to be responsible for this radioresistance. Herein, we will analyze the data supporting or not the cancer stem cell model in GBM, overview the current knowledge regarding GBM stem cell self-renewal and radioresistance molecular mechanisms, and discuss the potential therapeutic application of these findings

  17. What makes cancer stem cell markers different?

    OpenAIRE

    Karsten, Uwe; Goletz, Steffen

    2013-01-01

    Since the cancer stem cell concept has been widely accepted, several strategies have been proposed to attack cancer stem cells (CSC). Accordingly, stem cell markers are now preferred therapeutic targets. However, the problem of tumor specificity has not disappeared but shifted to another question: how can cancer stem cells be distinguished from normal stem cells, or more specifically, how do CSC markers differ from normal stem cell markers? A hypothesis is proposed which might help to solve t...

  18. Effect of small interfering RNA targeting survivin gene on biological behaviour of bladder cancer

    Institute of Scientific and Technical Information of China (English)

    HOU Jian-quan; HE Jun; WANG Xiao-lin; WEN Duan-gai; CHEN Zi-xing

    2006-01-01

    Background Bladder cancer is the most common type of urinary system tumours. It is frequently associated with genetic mutations that deregulate the cell cycle and render these tumours resistant to apoptosis. Survivin, a newly discovered member inhibitor of apoptosis protein (IAP) family in several human cancers, by inducing cell proliferation and inhibiting apoptosis is frequently activated in bladder cancer. We studied the influence of small interfering RNA (siRNA) targeting survivin on the biological behaviour of bladder cancer cells.Methods A double strand survivin target sequence specific siRNA was designed and synthesized. After transfection of bladder cancer cell line T24 by siRNA/liposome complex with increasing concentrations(50-200 nmol/L), the transfectant cells were intratumourally injected at different doses (5 μg or 50μg). The effects were measured in vitro and in vivo.Results The selected siRNA efficiently down-regulated survivin mRNA expression in a dose and time dependent manner. The maximal effect was achieved at the concentration of 100 nmol/L, at which survivin expression level was down-regulated by 75.91%. The inhibition rate of cell growth was 55.29% (P<0.01) and the markedly increased apoptotic rate was 45.70% (P<0.01). In vivo intratumoural injection of 50 μg siRNA-survivin could notably prevent the growth of bladder cancer (P<0.01) in xenografted animals.Conclusion The application of siRNA-survivin could markedly inhibit survivin expression in bladder cancer cell line by inducing apoptosis and inhibiting the growth of the tumour. It may become a new gene therapy tool for bladder cancer.

  19. Noncoding RNA small nucleolar RNA host gene 1 promote cell proliferation in nonsmall cell lung cancer

    Directory of Open Access Journals (Sweden)

    J You

    2014-01-01

    Full Text Available Background: Nonsmall cell lung cancer (NSCLC is the major cause of cancer death worldwide. Increasing evidence shows that noncoding RNAs (ncRNAs are widely involved in the development and progression of NSCLC. ncRNA small nucleolar RNA host gene 1 (SNHG1 has not been studied in cancer, especially its role in lung cancer remains unknown. Our studies were designed to investigate the expression and biological significance of SNHG1 in lung cancer. SNHG1 may be a novel ncRNA in early diagnosis in lung cancer. Methods: Noncoding RNA SNHG1 expression in 7 lung cancer cell lines was measured by quantitative real-time polymerase chain reaction. RNA interference approaches were used to find the biological functions of SNHG1. The effect of SNHG1 on proliferation was evaluated by cell count and crystal violet stains. Results: Noncoding RNA SNHG1 expression was significantly upregulated in lung cancer cells when compared with normal bronchial epithelial cells. In addition, in vitro assays our results indicated that knockdown of SNHG1 inhibited cell proliferation. Conclusions: Our data indicated that ncRNA SNHG1 is significantly upregulated in NSCLC cell lines and may represent a new biomarker and a potential therapeutic target for NSCLC intervention.

  20. Mathematical and Statistical Modeling in Cancer Systems Biology

    Directory of Open Access Journals (Sweden)

    Rachael eHageman Blair

    2012-06-01

    Full Text Available Cancer is a major health problem with high mortality rates. In the post-genome era, investigators have access to massive amounts of rapidly accumulating high-throughput data in publicly available databases, some of which are exclusively devoted to housing Cancer data. However, data interpretation efforts have not kept pace with data collection, and gained knowledge is not necessarily translating into better diagnoses and treatments. A fundamental problem is to integrate and interpret data to further our understanding in Cancer Systems Biology. Viewing cancer as a network provides insights into the complex mechanisms underlying the disease. Mathematical and statistical models provide an avenue for cancer network modeling. In this article, we review two widely used modeling paradigms: deterministic metabolic models and statistical graphical models. The strength of these approaches lies in their flexibility and predictive power. Once a model has been validated, it can be used to make predictions and generate hypotheses. We describe a number of diverse applications to Cancer Biology, including, the system-wide effects of drug-treatments, disease prognosis, tumor classification, forecasting treatment outcomes, and survival predictions.

  1. Cancer stem cells and resistance to chemo and radio therapy.

    Science.gov (United States)

    Malik, Babar; Nie, Daotai

    2012-01-01

    Cancer stem cells (CSCs, or tumor initiating cells) are responsible for tumor initiation. If cancer treatment kills most of cancer cells in the stage of transit amplifying and differentiation without killing the stem cells, the surviving CSCs will eventually lead to recurrence of tumors. Studies have suggested that CSCs may be the primary mediators of resistance to chemo- and radio-therapy, leading to failure in cancer therapy. Numerous targets are being investigated for their potential involvement in the self-renewal and chemo- and radio-resistance of cancer cells. However, despite the intensive efforts invested into characterizing the role of cancer stem cells, there is a sense of uncertainty regarding the identity and number of these cells as well as the implications in cancer treatment. In this review, we will discuss the identification of CSCs by cell surface markers, the biology of CSCs, and the role of CSCs in resistance to radio- and chemo-therapy. This review will discuss the advances in targeting CSCs to improve the efficacy of chemo- and radio-therapy. PMID:22202026

  2. Surgery for nonsmall cell lung cancer

    Directory of Open Access Journals (Sweden)

    Loïc Lang-Lazdunski

    2013-09-01

    Full Text Available Surgery remains the best curative option in patients with early stage lung cancer (stage I and II. Developments in minimally invasive techniques now allow surgeons to perform lung resections on elderly patients, patients with poor pulmonary function or significant cardiopulmonary comorbidities. New techniques, such as stereotactic radiotherapy and ablative procedures, are being evaluated in early-stage lung cancer and may represent an alternative to surgery in patients unfit for lung resection. Perioperative mortality rates have dropped significantly at most institutions in the past two decades and complications are managed more efficiently. Progress in imaging and staging techniques have helped cut futile thoracotomy rates and offer patients the most adequate treatment options. Large randomised trials have helped clarify the role of neoadjuvant, induction and adjuvant chemotherapy, as well as radiotherapy. Surgery remains an essential step in the multimodality therapy of selected patients with advanced-stage lung cancer (stage III and IV. Interventional and endoscopic techniques have reduced the role of surgery in the diagnosis and staging of nonsmall cell lung cancer, but surgery remains an important tool in the palliation of advanced-stage lung cancer. Large national/international surgical databases have been developed and predictive risk-models for surgical mortality/morbidity published by learned surgical societies. Nonetheless, lung cancer overall survival rates remain deceptively low and it is hoped that early detection/screening, better understanding of tumour biology and development of biomarkers, and development of efficient targeted therapies will help improve the prognosis of lung cancer patients in the next decade.

  3. Lung cancer - non-small cell

    Science.gov (United States)

    Cancer - lung - non-small cell; Non-small cell lung cancer; NSCLC; Adenocarcinoma - lung; Squamous cell carcinoma - lung ... Smoking causes most cases (around 90%) of lung cancer. The risk ... day and for how long you have smoked. Being around the smoke ...

  4. Breast cancer biology and ethnic disparities in breast cancer mortality in new zealand: a cohort study.

    Directory of Open Access Journals (Sweden)

    Sanjeewa Seneviratne

    Full Text Available Indigenous Māori women have a 60% higher breast cancer mortality rate compared with European women in New Zealand. We investigated differences in cancer biological characteristics and their impact on breast cancer mortality disparity between Māori and NZ European women.Data on 2849 women with primary invasive breast cancers diagnosed between 1999 and 2012 were extracted from the Waikato Breast Cancer Register. Differences in distribution of cancer biological characteristics between Māori and NZ European women were explored adjusting for age and socioeconomic deprivation in logistic regression models. Impacts of socioeconomic deprivation, stage and cancer biological characteristics on breast cancer mortality disparity between Māori and NZ European women were explored in Cox regression models.Compared with NZ European women (n=2304, Māori women (n=429 had significantly higher rates of advanced and higher grade cancers. Māori women also had non-significantly higher rates of ER/PR negative and HER-2 positive breast cancers. Higher odds of advanced stage and higher grade remained significant for Māori after adjusting for age and deprivation. Māori women had almost a 100% higher age and deprivation adjusted breast cancer mortality hazard compared with NZ European women (HR=1.98, 1.55-2.54. Advanced stage and lower proportion of screen detected cancer in Māori explained a greater portion of the excess breast cancer mortality (HR reduction from 1.98 to 1.38, while the additional contribution through biological differences were minimal (HR reduction from 1.38 to 1.35.More advanced cancer stage at diagnosis has the greatest impact while differences in biological characteristics appear to be a minor contributor for inequities in breast cancer mortality between Māori and NZ European women. Strategies aimed at reducing breast cancer mortality in Māori should focus on earlier diagnosis, which will likely have a greater impact on reducing breast

  5. Cancer Systems Biology: a peek into the future of patient care?

    Science.gov (United States)

    Werner, Henrica M J; Mills, Gordon B; Ram, Prahlad T

    2014-03-01

    Traditionally, scientific research has focused on studying individual events, such as single mutations, gene function, or the effect that mutating one protein has on a biological phenotype. A range of technologies is beginning to provide information that will enable a holistic view of how genomic and epigenetic aberrations in cancer cells can alter the homeostasis of signalling networks within these cells, between cancer cells and the local microenvironment, and at the organ and organism level. This process, termed Systems Biology, needs to be integrated with an iterative approach wherein hypotheses and predictions that arise from modelling are refined and constrained by experimental evaluation. Systems biology approaches will be vital for developing and implementing effective strategies to deliver personalized cancer therapy. Specifically, these approaches will be important to select those patients who are most likely to benefit from targeted therapies and for the development and implementation of rational combinatorial therapies. Systems biology can help to increase therapy efficacy or bypass the emergence of resistance, thus converting the current-often short term-effects of targeted therapies into durable responses, ultimately to improve patient quality of life and provide a cure. PMID:24492837

  6. Cancer-Specific Telomerase Reverse Transcriptase (TERT Promoter Mutations: Biological and Clinical Implications

    Directory of Open Access Journals (Sweden)

    Tiantian Liu

    2016-07-01

    Full Text Available The accumulated evidence has pointed to a key role of telomerase in carcinogenesis. As a RNA-dependent DNA polymerase, telomerase synthesizes telomeric DNA at the end of linear chromosomes, and attenuates or prevents telomere erosion associated with cell divisions. By lengthening telomeres, telomerase extends cellular life-span or even induces immortalization. Consistent with its functional activity, telomerase is silent in most human normal somatic cells while active only in germ-line, stem and other highly proliferative cells. In contrast, telomerase activation widely occurs in human cancer and the enzymatic activity is detectable in up to 90% of malignancies. Recently, hotspot point mutations in the regulatory region of the telomerase reverse transcriptase (TERT gene, encoding the core catalytic component of telomerase, was identified as a novel mechanism to activate telomerase in cancer. This review discusses the cancer-specific TERT promoter mutations and potential biological and clinical significances.

  7. Cancer-Specific Telomerase Reverse Transcriptase (TERT) Promoter Mutations: Biological and Clinical Implications

    Science.gov (United States)

    Liu, Tiantian; Yuan, Xiaotian; Xu, Dawei

    2016-01-01

    The accumulated evidence has pointed to a key role of telomerase in carcinogenesis. As a RNA-dependent DNA polymerase, telomerase synthesizes telomeric DNA at the end of linear chromosomes, and attenuates or prevents telomere erosion associated with cell divisions. By lengthening telomeres, telomerase extends cellular life-span or even induces immortalization. Consistent with its functional activity, telomerase is silent in most human normal somatic cells while active only in germ-line, stem and other highly proliferative cells. In contrast, telomerase activation widely occurs in human cancer and the enzymatic activity is detectable in up to 90% of malignancies. Recently, hotspot point mutations in the regulatory region of the telomerase reverse transcriptase (TERT) gene, encoding the core catalytic component of telomerase, was identified as a novel mechanism to activate telomerase in cancer. This review discusses the cancer-specific TERT promoter mutations and potential biological and clinical significances. PMID:27438857

  8. Cancer-Specific Telomerase Reverse Transcriptase (TERT) Promoter Mutations: Biological and Clinical Implications.

    Science.gov (United States)

    Liu, Tiantian; Yuan, Xiaotian; Xu, Dawei

    2016-01-01

    The accumulated evidence has pointed to a key role of telomerase in carcinogenesis. As a RNA-dependent DNA polymerase, telomerase synthesizes telomeric DNA at the end of linear chromosomes, and attenuates or prevents telomere erosion associated with cell divisions. By lengthening telomeres, telomerase extends cellular life-span or even induces immortalization. Consistent with its functional activity, telomerase is silent in most human normal somatic cells while active only in germ-line, stem and other highly proliferative cells. In contrast, telomerase activation widely occurs in human cancer and the enzymatic activity is detectable in up to 90% of malignancies. Recently, hotspot point mutations in the regulatory region of the telomerase reverse transcriptase (TERT) gene, encoding the core catalytic component of telomerase, was identified as a novel mechanism to activate telomerase in cancer. This review discusses the cancer-specific TERT promoter mutations and potential biological and clinical significances. PMID:27438857

  9. The Kynurenine Pathway in Stem Cell Biology

    OpenAIRE

    Jones, Simon P; Guillemin, Gilles J; Bruce J Brew

    2013-01-01

    The kynurenine pathway (KP) is the main catabolic pathway of the essential amino acid tryptophan. The KP has been identified to play a critical role in regulating immune responses in a variety of experimental settings. It is also known to be involved in several neuroinflammatory diseases including Huntington’s disease, amyotrophic lateral sclerosis, and Alzheimer’s disease. This review considers the current understanding of the role of the KP in stem cell biology. Both of these fundamental ar...

  10. Expression of Telomerase Activity in Gastric Cancer Cells

    Institute of Scientific and Technical Information of China (English)

    2002-01-01

    Objective To study the relationship between telomerase activity and biological behavior in human gastric cells and appraise the clinical significance of detecting telomerase activity. Methods The telomerase activity in 47 gastric cancer tissue samples,their matched nomal tissues,7 gastric ulcer and 2 gastric cancer cell lines was detected using a PCR-based non-radioisotopic telomeric repeat amplification protocol(TRAP) assay. Results None of the 47 samples from normal gastric tissues expressed telomerase activity.The 41 of 47 cases of gastric cancer presented telomerase activity with an 87.2% positive rate (P<0.001). 2/2 gastric cancer cell lines and 0/7 gastric ulcer line were also positive for telmerase activity.The activity of telomerase was associated with the pathological differentiation of gastric cancer. Conclusion Telomerase activity may be related to the biological behavior of gastric cancer and can help in assessing the malignant poten-tial of gastric cancer.Telomerase activity will be a good diagnostic marker for the detection of gastric cancer.

  11. Biological cell manipulation by magnetic nanoparticles

    Science.gov (United States)

    Gertz, Frederick; Khitun, Alexander

    2016-02-01

    We report a manipulation of biological cells (erythrocytes) by magnetite (Fe3O4) nanoparticles in the presence of a magnetic field. The experiment was accomplished on the top of a micro-electromagnet consisting of two magnetic field generating contours. An electric current flowing through the contour(s) produces a non-uniform magnetic field, which is about 1.4 mT/μm in strength at 100 mA current in the vicinity of the current-carrying wire. In responses to the magnetic field, magnetic nanoparticles move towards the systems energy minima. In turn, magnetic nanoparticles drag biological cells in the same direction. We present experimental data showing cell manipulation through the control of electric current. This technique allows us to capture and move cells located in the vicinity (10-20 microns) of the current-carrying wires. One of the most interesting results shows a periodic motion of erythrocytes between the two conducting contours, whose frequency is controlled by an electric circuit. The obtained results demonstrate the feasibility of non-destructive cell manipulation by magnetic nanoparticles with micrometer-scale precision.

  12. Colorectal Cancer Stem Cells and Cell Death

    International Nuclear Information System (INIS)

    Nowadays it is reported that, similarly to other solid tumors, colorectal cancer is sustained by a rare subset of cancer stem–like cells (CSCs), which survive conventional anticancer treatments, thanks to efficient mechanisms allowing escape from apoptosis, triggering tumor recurrence. To improve patient outcomes, conventional anticancer therapies have to be replaced with specific approaches targeting CSCs. In this review we provide strong support that BMP4 is an innovative therapeutic approach to prevent colon cancer growth increasing differentiation markers expression and apoptosis. Recent data suggest that in colorectal CSCs, protection from apoptosis is achieved by interleukin-4 (IL-4) autocrine production through upregulation of antiapoptotic mediators, including survivin. Consequently, IL-4 neutralization could deregulate survivin expression and localization inducing chemosensitivity of the colon CSCs pool

  13. The relationship of cancer stem cells in urological cancers

    OpenAIRE

    Marta Pokrywczyńska; Jan Adamowicz; Jakub Tworkiewicz; Zbigniew Wolski; Tomasz Drewa

    2013-01-01

    Numerous studies are ongoing to identify and isolate cancer stem cells from cancers of genito-urinary tracts. Better understanding of their role in prostate, urothelial and kidney cancer origin, growth and progression opens new pathways in development of more effective treatment methods. However there are still many issues before advances in this field can be introduced for clinical application. This review addresses current achievements in cancer stem cells research in uro-oncology.

  14. The relationship of cancer stem cells in urological cancers

    Directory of Open Access Journals (Sweden)

    Marta Pokrywczyńska

    2013-08-01

    Full Text Available Numerous studies are ongoing to identify and isolate cancer stem cells from cancers of genito-urinary tracts. Better understanding of their role in prostate, urothelial and kidney cancer origin, growth and progression opens new pathways in development of more effective treatment methods. However there are still many issues before advances in this field can be introduced for clinical application. This review addresses current achievements in cancer stem cells research in uro-oncology.

  15. Glutathione in Cancer Cell Death

    International Nuclear Information System (INIS)

    Glutathione (L-γ-glutamyl-L-cysteinyl-glycine; GSH) in cancer cells is particularly relevant in the regulation of carcinogenic mechanisms; sensitivity against cytotoxic drugs, ionizing radiations, and some cytokines; DNA synthesis; and cell proliferation and death. The intracellular thiol redox state (controlled by GSH) is one of the endogenous effectors involved in regulating the mitochondrial permeability transition pore complex and, in consequence, thiol oxidation can be a causal factor in the mitochondrion-based mechanism that leads to cell death. Nevertheless GSH depletion is a common feature not only of apoptosis but also of other types of cell death. Indeed rates of GSH synthesis and fluxes regulate its levels in cellular compartments, and potentially influence switches among different mechanisms of death. How changes in gene expression, post-translational modifications of proteins, and signaling cascades are implicated will be discussed. Furthermore, this review will finally analyze whether GSH depletion may facilitate cancer cell death under in vivo conditions, and how this can be applied to cancer therapy

  16. Glutathione in Cancer Cell Death

    Energy Technology Data Exchange (ETDEWEB)

    Ortega, Angel L. [Department of Physiology, Faculty of Medicine and Odontology, University of Valencia, 17 Av. Blasco Ibanez, 46010 Valencia (Spain); Mena, Salvador [Green Molecular SL, Pol. Ind. La Coma-Parc Cientific, 46190 Paterna, Valencia (Spain); Estrela, Jose M., E-mail: jose.m.estrela@uv.es [Department of Physiology, Faculty of Medicine and Odontology, University of Valencia, 17 Av. Blasco Ibanez, 46010 Valencia (Spain)

    2011-03-11

    Glutathione (L-γ-glutamyl-L-cysteinyl-glycine; GSH) in cancer cells is particularly relevant in the regulation of carcinogenic mechanisms; sensitivity against cytotoxic drugs, ionizing radiations, and some cytokines; DNA synthesis; and cell proliferation and death. The intracellular thiol redox state (controlled by GSH) is one of the endogenous effectors involved in regulating the mitochondrial permeability transition pore complex and, in consequence, thiol oxidation can be a causal factor in the mitochondrion-based mechanism that leads to cell death. Nevertheless GSH depletion is a common feature not only of apoptosis but also of other types of cell death. Indeed rates of GSH synthesis and fluxes regulate its levels in cellular compartments, and potentially influence switches among different mechanisms of death. How changes in gene expression, post-translational modifications of proteins, and signaling cascades are implicated will be discussed. Furthermore, this review will finally analyze whether GSH depletion may facilitate cancer cell death under in vivo conditions, and how this can be applied to cancer therapy.

  17. Celebrating Plant Cells: A Special Issue on Plant Cell Biology

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    @@ A special issue on plant cell biology is long overdue for JIPB! In the last two decades or so, the plant biology community has been thrilled by explosive discoveries regarding the molecular and genetic basis of plant growth, development, and responses to the environment, largely owing to recent maturation of model systems like Arabidopsis thaliana and the rice Oryza sativa, as well as the rapid development of high throughput technologies associated with genomics and proteomics.

  18. A Synthetic Biology Approach Reveals a CXCR4-G13-Rho Signaling Axis Driving Transendothelial Migration of Metastatic Breast Cancer Cells

    OpenAIRE

    Yagi, Hiroshi; Tan, Wenfu; Dillenburg-Pilla, Patricia; Armando, Sylvain; Amornphimoltham, Panomwat; Simaan, May; Weigert, Roberto; Molinolo, Alfredo A.; Bouvier, Michel; Gutkind, J. Silvio

    2011-01-01

    Tumor cells can co-opt the pro-migratory activity of chemokines and their cognate G protein-coupled receptors (GPCRs) to metastasize to regional lymph nodes or distant organs. Indeed, the migration toward SDF-1 (stromal cell-derived factor-1) of tumor cells bearing CXCR4 [chemokine (C-X-C motif) receptor 4] has been implicated in the lymphatic and organ-specific metastasis of various human malignancies. Here, we used chimeric G proteins and GPCRs activated solely by artificial ligands to sele...

  19. [Dendritic cells in cancer immunotherapy].

    Science.gov (United States)

    Gato, M; Liechtenstein, T; Blanco-Luquín, I; Zudaire, M I; Kochan, G; Escors, D

    2015-01-01

    Since the beginning of the 20th century, biomedical scientists have tried to take advantage of the natural anti-cancer activities of the immune system. However, all the scientific and medical efforts dedicated to this have not resulted in the expected success. In fact, classical antineoplastic treatments such as surgery, radio and chemotherapy are still first line treatments. Even so, there is a quantity of experimental evidence demonstrating that cancer cells are immunogenic. However, the effective activation of anti-cancer T cell responses closely depends on an efficient antigen presentation carried out by professional antigen presenting cells such as DC. Although there are a number of strategies to strengthen antigen presentation by DC, anti-cancer immunotherapy is not as effective as we would expect according to preclinical data accumulated in recent decades. We do not aim to make an exhaustive review of DC immunotherapy here, which is an extensive research subject already dealt with in many specialised reviews. Instead, we present the experimental approaches undertaken by our group over the last decade, by modifying DC to improve their anti-tumour capacities. PMID:26486534

  20. Metabolic oxidative stress in cancer biology and therapy

    International Nuclear Information System (INIS)

    Cancer cells (relative to normal cells) exhibit increased glycolysis and pentose cycle activity. These metabolic alterations were thought to arise from damage to the respiratory mechanism and cancer cells were thought to compensate for this defect by increasing glycolysis (Science 132:309). In addition to its role in ATP production, glucose metabolism results in the formation of pyruvate and NADPH which both play an integral role in peroxide detoxification (Ann. NY Acad. Sci. 899:349). Recently, cancer cells have been shown to have enhanced susceptibility to glucose deprivation-induced oxidative stress, relative to normal cells, that is mediated by reactive oxygen species (ROS; Biochem.J. 418:29-37). These results support the hypothesis that cancer cells may have a defect in mitochondrial respiration leading to increased steady-state levels of ROS (i.e., O2 and H2O2) and glucose metabolism may be increased to provide reducing equivalents to compensate for this defect. The application of these findings to developing new combined modality cancer therapy protocols will be discussed. (author)

  1. Cancer Stem Cell Radioresistance and Enrichment: Where Frontline Radiation Therapy May Fail in Lung and Esophageal Cancers

    International Nuclear Information System (INIS)

    Many studies have highlighted the role cancer stem cells (CSC) play in the development and progression of various types of cancer including lung and esophageal cancer. More recently, it has been proposed that the presence of CSCs affects treatment efficacy and patient prognosis. In reviewing this new area of cancer biology, we will give an overview of the current literature regarding lung and esophageal CSCs and radioresistance of CSC, and discuss the potential therapeutic applications of these findings

  2. The biological approach to the radiotherapy of the oral cancers of South India

    International Nuclear Information System (INIS)

    Two-thirds of all cancers in South India are squamous cell carcinomas, of which 78% to 93% are late cases requiring radiotherapy. Oral cancers, which constitute the majority of these, provided an excellent clinical model for studies in radiotherapeutic biology. Their characteristics made them ideally suited for our clinical trials. The paper reviews the special biology of these lesions, the factors involved in their radiation non-response, the therapeutic postulations that suggested themselves, the implementation of these therapeutic protocols and the mixed story of failure and success that has marked the two decades of these studies. It discovers the fact that radiation response is not just a factor of tumor extent but involves several biological subleties in both tumor and its host environment. It also discusses possible future approaches to bridge a gap of about 30% failure in these lesions, especially in the context of a poor economy. (orig.)

  3. Nitric oxide induces cancer stem cell-like phenotypes in human lung cancer cells.

    Science.gov (United States)

    Yongsanguanchai, Nuttida; Pongrakhananon, Varisa; Mutirangura, Apiwat; Rojanasakul, Yon; Chanvorachote, Pithi

    2015-01-15

    Even though tremendous advances have been made in the treatment of cancers during the past decades, the success rate among patients with cancer is still dismal, largely because of problems associated with chemo/radioresistance and relapse. Emerging evidence has indicated that cancer stem cells (CSCs) are behind the resistance and recurrence problems, but our understanding of their regulation is limited. Rapid reversible changes of CSC-like cells within tumors may result from the effect of biological mediators found in the tumor microenvironment. Here we show how nitric oxide (NO), a key cellular modulator whose level is elevated in many tumors, affects CSC-like phenotypes of human non-small cell lung carcinoma H292 and H460 cells. Exposure of NO gradually altered the cell morphology toward mesenchymal stem-like shape. NO exposure promoted CSC-like phenotype, indicated by increased expression of known CSC markers, CD133 and ALDH1A1, in the exposed cells. These effects of NO on stemness were reversible after cessation of the NO treatment for 7 days. Furthermore, such effect was reproducible using another NO donor, S-nitroso-N-acetylpenicillamine. Importantly, inhibition of NO by the known NO scavenger 2-(4-carboxy-phenyl)-4,4,5,5 tetramethylimidazoline-1-oxy-3-oxide strongly inhibited CSC-like aggressive cellular behavior and marker expression. Last, we unveiled the underlying mechanism of NO action through the activation of caveolin-1 (Cav-1), which is upregulated by NO and is responsible for the aggressive behavior of the cells, including anoikis resistance, anchorage-independent cell growth, and increased cell migration and invasion. These findings indicate a novel role of NO in CSC regulation and its importance in aggressive cancer behaviors through Cav-1 upregulation. PMID:25411331

  4. Prostate Cancer Stem Cells: Research Advances

    Directory of Open Access Journals (Sweden)

    Dagmara Jaworska

    2015-11-01

    Full Text Available Cancer stem cells have been defined as cells within a tumor that possesses the capacity to self-renew and to cause the heterogeneous lineages of cancer cells that comprise the tumor. Experimental evidence showed that these highly tumorigenic cells might be responsible for initiation and progression of cancer into invasive and metastatic disease. Eradicating prostate cancer stem cells, the root of the problem, has been considered as a promising target in prostate cancer treatment to improve the prognosis for patients with advanced stages of the disease.

  5. Cancer Stem Cells, Epithelial to Mesenchymal Markers, and Circulating Tumor Cells in Small Cell Lung Cancer

    NARCIS (Netherlands)

    Pore, Milind; Meijer, Coby; de Bock, Geertruida H; Boersma-van Ek, Wytske; Terstappen, Leon W M M; Groen, Harry J M; Timens, Wim; Kruyt, Frank A E; Hiltermann, T Jeroen N

    2016-01-01

    BACKGROUND: Small cell lung cancer (SCLC) has a poor prognosis, and even with localized (limited) disease, the 5-year survival has only been around 20%. Elevated levels of circulating tumor cells (CTCs) have been associated with a worse prognosis, and markers of cancer stem cells (CSCs) and epitheli

  6. Extinction Models for Cancer Stem Cell Therapy

    OpenAIRE

    Sehl, Mary; Zhou, Hua; Sinsheimer, Janet ,; Lange, Kenneth

    2009-01-01

    Cells with stem cell-like properties are now viewed as initiating and sustaining many cancers. This suggests that cancer can be cured by driving these cancer stem cells to extinction. The problem with this strategy is that ordinary stem cells are apt to be killed in the process. This paper sets bounds on the killing differential (difference between death rates of cancer stem cells and normal stem cells) that must exist for the survival of an adequate number of normal stem cells. Our main tool...

  7. Impact of 18FDG-PET/CT on biological target volume (BTV) definition for treatment planning for non-small cell lung cancer patients

    Science.gov (United States)

    Devic, Slobodan; Tomic, Nada; Faria, Sergio; Dean, Geoffrey; Lisbona, Robert; Parker, William; Kaufman, Chris; Podgorsak, Ervin B.

    2007-02-01

    This work represents our effort to test feasibility of FDG-based PET/CT on target volume delineation in radiotherapy treatment planning of NSCLC patients. Different methods have been developed to enable more precise target outlining using PET: Qualitative Visual Method, CTV=2.5 SUV units, linear SUV threshold function method, and CTV=40% Iso of Maximum Uptake Value. We are proposing reconstruction of three biological target volumes: necrotic BTV (same as PTV created by radiation oncologist using CT data), proliferating BTV (based on PET signal to background ratio 1:3) and hypoxic BTV (based on PET signal to background ratio of 1:19). Two IMRT plans were created and compared to the conventional treatment plan: "conservative" IMRT plan delivers 52.5 Gy to the necrotic BTV and 65 Gy to the hypoxic BTV; "radical" IMRT plan delivers 30 Gy to necrotic BTV, 52.5 Gy to proliferating BTV and 65 Gy to hypoxic BTV. Use of BTVs in IMRT plans is attractive because it increases dose to targets considered to need higher doses. It reduces considerably dose to heart and spinal cord, organs considered to limit dose escalation approaches in NSCLC treatment. "Conservative" IMRT approach can be understood as a PET/CT-based concomitant boost to the tumor expressing the highest FDG uptake. "Radical" plan implies deviation from the traditional uniform dose target coverage approach, with the intention of achieving better surrounding tissue sparing and ultimately allowing for dose escalation protocols relying on biologically based treatment planning.

  8. Impact of 18FDG-PET/CT on biological target volume (BTV) definition for treatment planning for non-small cell lung cancer patients

    International Nuclear Information System (INIS)

    This work represents our effort to test feasibility of FDG-based PET/CT on target volume delineation in radiotherapy treatment planning of NSCLC patients. Different methods have been developed to enable more precise target outlining using PET: Qualitative Visual Method, CTV=2.5 SUV units, linear SUV threshold function method, and CTV=40% Iso of Maximum Uptake Value. We are proposing reconstruction of three biological target volumes: necrotic BTV (same as PTV created by radiation oncologist using CT data), proliferating BTV (based on PET signal to background ratio 1:3) and hypoxic BTV (based on PET signal to background ratio of 1:19). Two IMRT plans were created and compared to the conventional treatment plan: 'conservative' IMRT plan delivers 52.5 Gy to the necrotic BTV and 65 Gy to the hypoxic BTV; 'radical' IMRT plan delivers 30 Gy to necrotic BTV, 52.5 Gy to proliferating BTV and 65 Gy to hypoxic BTV. Use of BTVs in IMRT plans is attractive because it increases dose to targets considered to need higher doses. It reduces considerably dose to heart and spinal cord, organs considered to limit dose escalation approaches in NSCLC treatment. 'Conservative' IMRT approach can be understood as a PET/CT-based concomitant boost to the tumor expressing the highest FDG uptake. 'Radical' plan implies deviation from the traditional uniform dose target coverage approach, with the intention of achieving better surrounding tissue sparing and ultimately allowing for dose escalation protocols relying on biologically based treatment planning

  9. Cancer stem cells: the lessons from pre-cancerous stem cells

    OpenAIRE

    Gao, Jian-Xin

    2007-01-01

    Abstract How a cancer is initiated and established remains elusive despite all the advances in decades of cancer research. Recently the cancer stem cell (CSC) hypothesis has been revived, challenging the long-standing model of ‘clonal evolution’ for cancer development and implicating the dawning of a potential cure for cancer [1]. The recent identification of pre-cancerous stem cells (pCSCs) in cancer, an early stage of CSC development, however, implicates that the clonal evolution is not con...

  10. FR901228 in Treating Patients With Refractory or Progressive Small Cell Lung Cancer or Non-small Cell Lung Cancer

    Science.gov (United States)

    2013-08-14

    Extensive Stage Small Cell Lung Cancer; Stage IIIA Non-small Cell Lung Cancer; Stage IV Non-small Cell Lung Cancer; Recurrent Small Cell Lung Cancer; Stage IIIB Non-small Cell Lung Cancer; Recurrent Non-small Cell Lung Cancer

  11. Establishment and characterization of primary lung cancer cell lines from Chinese population

    Institute of Scientific and Technical Information of China (English)

    Chao ZHENG; Yi-hua SUN; Xiao-lei YE; Hai-quan CHEN; Hong-bin JI

    2011-01-01

    Aim: To establish and characterize primary lung cancer cell lines from Chinese population.Methods: Lung cancer specimens or pleural effusions were collected from Chinese lung cancer patients and cultured in vitro with ACL4 medium (for non-small cell lung carcinomas (NSCLC)) or HITES medium (for small cell lung carcinomas (SCLC)) supplemented with 5%FBS. All cell lines were maintained in culture for more than 25 passages. Most of these cell lines were further analyzed for oncogenic mutations, karyotype, cell growth kinetics, and tumorigenicity in nude mice.Results: Eight primary cell lines from Chinese lung cancer patients were established and characterized, including seven NSCLC cell lines and one SCLC cell line. Five NSCLC cell lines were found to harbor epidermal growth factor receptor (EGFR) kinase domain mutations.Conclusion: These well-characterized primary lung cancer cell lines from Chinese population provide a unique platform for future studies of the ethnic differences in lung cancer biology and drug response.

  12. The Cancer Stem Cell Concept in Progression of Head and Neck Cancer

    OpenAIRE

    Zhuo Chen

    2009-01-01

    Human head and neck cancer (HNC) is a highly heterogeneous disease. Understanding the biology of HNC progression is necessary for the development of novel approaches to its prevention, early detection, and treatment. A current evolutional progression model has limitations in explaining the heterogeneity observed in a single tumor nest. Accumulating evidence supports the existence of cancer stem cells (CSCs) as small subpopulations in solid tumors, including HNC. These CSCs can be selected by ...

  13. Implications of the Cancer Stem-Cell Hypothesis for Breast Cancer Prevention and Therapy

    OpenAIRE

    Kakarala, Madhuri; Wicha, Max S.

    2008-01-01

    Recent research in breast biology has provided support for the cancer stem-cell hypothesis. Two important components of this hypothesis are that tumors originate in mammary stem or progenitor cells as a result of dysregulation of the normally tightly regulated process of self-renewal. As a result, tumors contain and are driven by a cellular subcomponent that retains key stem-cell properties including self-renewal, which drives tumorigenesis and differentiation that contributes to cellular het...

  14. Breast cancer stem cells: implications for therapy of breast cancer

    OpenAIRE

    Morrison, Brian J.; Schmidt, Chris W.; Lakhani, Sunil R; Reynolds, Brent A.; Lopez, J. Alejandro

    2008-01-01

    The concept of cancer stem cells responsible for tumour origin, maintenance, and resistance to treatment has gained prominence in the field of breast cancer research. The therapeutic targeting of these cells has the potential to eliminate residual disease and may become an important component of a multimodality treatment. Recent improvements in immunotherapy targeting of tumour-associated antigens have advanced the prospect of targeting breast cancer stem cells, an approach that might lead to...

  15. Anticoagulant drugs increase natural killer cell activity in lung cancer

    Czech Academy of Sciences Publication Activity Database

    Bobek, M.; Boubelík, Michael; Fišerová, Anna; Luptovcová, Martina; Vannucci, Luca; Kacprzak, G.; Kolodzej, J.; Majewski, A.M.; Hoffman, R. M.

    2005-01-01

    Roč. 47, č. 2 (2005), s. 215-223. ISSN 0169-5002 Institutional research plan: CEZ:AV0Z5052915 Keywords : anticoagulant drugs * lung cancer * NK cells Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 3.172, year: 2005

  16. Genetically modified dendritic cell-based cancer vaccines

    Czech Academy of Sciences Publication Activity Database

    Bubeník, Jan

    2001-01-01

    Roč. 47, č. 5 (2001), s. 153-155. ISSN 0015-5500 R&D Projects: GA MZd NC5526 Keywords : dendritic cells * cancer vaccines Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 0.519, year: 2001

  17. The migration ability of stem cells can explain the existence of cancer of unknown primary site. Rethinking metastasis

    OpenAIRE

    López-Lázaro, Miguel

    2015-01-01

    Cancers of unknown primary site are metastatic cancers for which primary tumors are not found after detailed investigations. In many cases, the site of origin is not identified even on postmortem examination. These cancers are the fourth most common cause of cancer death. The biological events involved in the development of this type of cancers remain unknown. This manuscript discusses that, like metastatic cells, stem cells have a natural ability to migrate. A cancer of unknown primary site ...

  18. Biological and therapeutic impact of intratumor heterogeneity in cancer evolution.

    Science.gov (United States)

    McGranahan, Nicholas; Swanton, Charles

    2015-01-12

    Precision medicine requires an understanding of cancer genes and mutational processes, as well as an appreciation of the extent to which these are found heterogeneously in cancer cells during tumor evolution. Here, we explore the processes shaping the cancer genome, placing these within the context of tumor evolution and their impact on intratumor heterogeneity and drug development. We review evidence for constraints and contingencies to tumor evolution and highlight the clinical implications of diversity within tumors. We outline the limitations of genome-driven targeted therapies and explore future strategies, including immune and adaptive approaches, to address this therapeutic challenge. PMID:25584892

  19. Cancer Stem Cells Converted from Pluripotent Stem Cells and the Cancerous Niche

    OpenAIRE

    Kasai, T; Chen, L.; Mizutani, AZ; Kudoh, T.; Murakami, H; Fu, L.; Seno, M

    2014-01-01

    Nowadays, the cancer stem cells are considered to be significantly responsible for growth, metastasis, invasion and recurrence of all cancer. Cancer stem cells are typically characterized by continuous proliferation and self-renewal as well as by differentiation potential, while stem cells are considered to differentiate into tissue- specific phenotype of mature cells under the influence of micro-environment. Cancer stem cells should be traced to the stem cells under the influence of a micro-...

  20. Cancer stem cells in head and neck cancer

    OpenAIRE

    Trapasso S; Allegra E

    2012-01-01

    Eugenia Allegra, Serena TrapassoOtolaryngology – Head and Neck Surgery, University Magna Graecia of Catanzaro, Catanzaro, ItalyAbstract: Cancer stem cells (CSCs), also called "cells that start the tumor," represent in themselves one of the most topical and controversial issues in the field of cancer research. Tumor stem cells are able to self-propagate in vitro (self-renewal), giving rise both to other tumor stem cells and most advanced cells in the line of differe...

  1. Crosstalk between cancer cells and bone microenvironment in bone metastasis

    International Nuclear Information System (INIS)

    Bone, as well as lung and liver, is one of the most preferential metastatic target sites for cancers including breast, prostate, and lung cancers. Although the precise molecular mechanisms underlying this preference need to be elucidated, it appears that bone microenvironments possess unique biological features that enable circulating cancer cells to home, survive and proliferate, and destroy bone. In conjunction, cancers that develop bone metastases likely have the capacity to utilize these unique bone environments for colonization and bone destruction. This crosstalk between metastatic cancer cells and bone is critical to the development and progression of bone metastases. Disruption of this interaction will allow us to design mechanism-based effective and specific therapeutic interventions for bone metastases

  2. Cancer Stem Cells and Side Population Cells in Breast Cancer and Metastasis

    OpenAIRE

    Lennard, Thomas W.J.; Meeson, Annette P; Britton, Kelly M.; Kirby, John A.

    2011-01-01

    In breast cancer it is never the primary tumour that is fatal; instead it is the development of metastatic disease which is the major cause of cancer related mortality. There is accumulating evidence that suggests that Cancer Stem Cells (CSC) may play a role in breast cancer development and progression. Breast cancer stem cell populations, including side population cells (SP), have been shown to be primitive stem cell-like populations, being long-lived, self-renewing and highly proliferative....

  3. Mutant p53: multiple mechanisms define biologic activity in cancer

    Directory of Open Access Journals (Sweden)

    Michael Paul Kim

    2015-11-01

    Full Text Available The functional importance of p53 as a tumor suppressor gene is evident through its pervasiveness in cancer biology. The p53 gene is the most commonly altered gene in human cancer; however, not all genetic alterations are biologically equivalent. The majority of p53 alterations involve missense mutations that result in the production of mutant p53 proteins. Such mutant p53 proteins lack normal p53 function and may acquire novel functions, often with deleterious effects. Here, we review characterized mechanisms of mutant p53 gain of function in multiple model systems. In addition, we review mutant p53 addiction as emerging evidence suggests that tumors may depend on sustained mutant p53 activity for continued growth. We also discuss the role of p53 in stromal elements and their contribution to tumor initiation and progression. Lastly, current genetic mouse models of mutant p53 are reviewed and their limitations discussed.

  4. Systems Biology for Organotypic Cell Cultures

    Energy Technology Data Exchange (ETDEWEB)

    Grego, Sonia [RTI International, Research Triangle Park, NC (United States); Dougherty, Edward R. [Texas A & M Univ., College Station, TX (United States); Alexander, Francis J. [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Auerbach, Scott S. [National Inst. of Environmental Health Sciences, Research Triangle Park, NC (United States); Berridge, Brian R. [GlaxoSmithKline, Research Triangle Park, NC (United States); Bittner, Michael L. [Translational Genomics Research Inst., Phoenix, AZ (United States); Casey, Warren [National Inst. of Environmental Health Sciences, Research Triangle Park, NC (United States); Cooley, Philip C. [RTI International, Research Triangle Park, NC (United States); Dash, Ajit [HemoShear Therapeutics, Charlottesville, VA (United States); Ferguson, Stephen S. [National Inst. of Environmental Health Sciences, Research Triangle Park, NC (United States); Fennell, Timothy R. [RTI International, Research Triangle Park, NC (United States); Hawkins, Brian T. [RTI International, Research Triangle Park, NC (United States); Hickey, Anthony J. [RTI International, Research Triangle Park, NC (United States); Kleensang, Andre [Johns Hopkins Univ., Baltimore, MD (United States). Center for Alternatives to Animal Testing; Liebman, Michael N. [IPQ Analytics, Kennett Square, PA (United States); Martin, Florian [Phillip Morris International, Neuchatel (Switzerland); Maull, Elizabeth A. [National Inst. of Environmental Health Sciences, Research Triangle Park, NC (United States); Paragas, Jason [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States); Qiao, Guilin [Defense Threat Reduction Agency, Ft. Belvoir, VA (United States); Ramaiahgari, Sreenivasa [National Inst. of Environmental Health Sciences, Research Triangle Park, NC (United States); Sumner, Susan J. [RTI International, Research Triangle Park, NC (United States); Yoon, Miyoung [The Hamner Inst. for Health Sciences, Research Triangle Park, NC (United States); ScitoVation, Research Triangle Park, NC (United States)

    2016-08-04

    Translating in vitro biological data into actionable information related to human health holds the potential to improve disease treatment and risk assessment of chemical exposures. While genomics has identified regulatory pathways at the cellular level, translation to the organism level requires a multiscale approach accounting for intra-cellular regulation, inter-cellular interaction, and tissue/organ-level effects. Tissue-level effects can now be probed in vitro thanks to recently developed systems of three-dimensional (3D), multicellular, “organotypic” cell cultures, which mimic functional responses of living tissue. However, there remains a knowledge gap regarding interactions across different biological scales, complicating accurate prediction of health outcomes from molecular/genomic data and tissue responses. Systems biology aims at mathematical modeling of complex, non-linear biological systems. We propose to apply a systems biology approach to achieve a computational representation of tissue-level physiological responses by integrating empirical data derived from organotypic culture systems with computational models of intracellular pathways to better predict human responses. Successful implementation of this integrated approach will provide a powerful tool for faster, more accurate and cost-effective screening of potential toxicants and therapeutics. On September 11, 2015, an interdisciplinary group of scientists, engineers, and clinicians gathered for a workshop in Research Triangle Park, North Carolina, to discuss this ambitious goal. Participants represented laboratory-based and computational modeling approaches to pharmacology and toxicology, as well as the pharmaceutical industry, government, non-profits, and academia. Discussions focused on identifying critical system perturbations to model, the computational tools required, and the experimental approaches best suited to generating key data. This consensus report summarizes the discussions held.

  5. Skeletal Muscle Stem Cells from Animals I. Basic Cell Biology

    OpenAIRE

    Michael V. Dodson, Gary J. Hausman, LeLuo Guan, Min Du, Theodore P. Rasmussen, Sylvia P. Poulos, Priya Mir, Werner G. Bergen, Melinda E. Fernyhough, Douglas C. McFarland, Robert P. Rhoads, Beatrice Soret, James M. Reecy, Sandra G. Velleman, Zhihua Jiang

    2010-01-01

    Skeletal muscle stem cells from food-producing animals are of interest to agricultural life scientists seeking to develop a better understanding of the molecular regulation of lean tissue (skeletal muscle protein hypertrophy) and intramuscular fat (marbling) development. Enhanced understanding of muscle stem cell biology and function is essential for developing technologies and strategies to augment the metabolic efficiency and muscle hypertrophy of growing animals potentially leading to grea...

  6. Skeletal muscle stem cells from animals I. basic cell biology

    OpenAIRE

    Dodson, Michael V.; Hausman, Gary J.; Guan, Leluo; Du, Min; Rasmussen, Theodore P.; Poulos, Sylvia P; Mir, Priya; Bergen, Werner G.; Fernyhough, Melinda E.; McFarland, Douglas C.; Rhoads, Robert P.; Soret Lafraya, Beatriz; Reecy, James M.; Velleman, Sandra G; Jiang, Zhihua

    2010-01-01

    Skeletal muscle stem cells from food-producing animals are of interest to agricultural life scientists seeking to develop a better understanding of the molecular regulation of lean tissue (skeletal muscle protein hypertrophy) and intramuscular fat (marbling) development. Enhanced understanding of muscle stem cell biology and function is essential for developing technologies and strategies to augment the metabolic efficiency and muscle hypertrophy of growing animals potentially leading to grea...

  7. Combining Physical and Biologic Parameters to Predict Radiation-Induced Lung Toxicity in Patients With Non-Small-Cell Lung Cancer Treated With Definitive Radiation Therapy

    Energy Technology Data Exchange (ETDEWEB)

    Stenmark, Matthew H. [Department of Radiation Oncology, University of Michigan Medical Center, Ann Arbor, Michigan (United States); Cai Xuwei [Department of Radiation Oncology, University of Michigan Medical Center, Ann Arbor, Michigan (United States); Radiation Oncology, Shanghai Cancer Hospital, Fudan University, Shanghai (China); Shedden, Kerby [Department of Biostatistics, University of Michigan Medical Center, Ann Arbor, Michigan (United States); Hayman, James A. [Department of Radiation Oncology, University of Michigan Medical Center, Ann Arbor, Michigan (United States); Yuan Shuanghu [Department of Radiation Oncology, University of Michigan Medical Center, Ann Arbor, Michigan (United States); Radiation Oncology, Shangdong Cancer Hospital, Jinan (China); Ritter, Timothy [Veterans Affairs Medical Center, Ann Arbor, Michigan (United States); Ten Haken, Randall K.; Lawrence, Theodore S. [Department of Radiation Oncology, University of Michigan Medical Center, Ann Arbor, Michigan (United States); Kong Fengming, E-mail: fengkong@med.umich.edu [Department of Radiation Oncology, University of Michigan Medical Center, Ann Arbor, Michigan (United States); Veterans Affairs Medical Center, Ann Arbor, Michigan (United States)

    2012-10-01

    Purpose: To investigate the plasma dynamics of 5 proinflammatory/fibrogenic cytokines, including interleukin-1beta (IL-1{beta}), IL-6, IL-8, tumor necrosis factor alpha (TNF-{alpha}), and transforming growth factor beta1 (TGF-{beta}1) to ascertain their value in predicting radiation-induced lung toxicity (RILT), both individually and in combination with physical dosimetric parameters. Methods and Materials: Treatments of patients receiving definitive conventionally fractionated radiation therapy (RT) on clinical trial for inoperable stages I-III lung cancer were prospectively evaluated. Circulating cytokine levels were measured prior to and at weeks 2 and 4 during RT. The primary endpoint was symptomatic RILT, defined as grade 2 and higher radiation pneumonitis or symptomatic pulmonary fibrosis. Minimum follow-up was 18 months. Results: Of 58 eligible patients, 10 (17.2%) patients developed RILT. Lower pretreatment IL-8 levels were significantly correlated with development of RILT, while radiation-induced elevations of TGF-ss1 were weakly correlated with RILT. Significant correlations were not found for any of the remaining 3 cytokines or for any clinical or dosimetric parameters. Using receiver operator characteristic curves for predictive risk assessment modeling, we found both individual cytokines and dosimetric parameters were poor independent predictors of RILT. However, combining IL-8, TGF-ss1, and mean lung dose into a single model yielded an improved predictive ability (P<.001) compared to either variable alone. Conclusions: Combining inflammatory cytokines with physical dosimetric factors may provide a more accurate model for RILT prediction. Future study with a larger number of cases and events is needed to validate such findings.

  8. Combining Physical and Biologic Parameters to Predict Radiation-Induced Lung Toxicity in Patients With Non-Small-Cell Lung Cancer Treated With Definitive Radiation Therapy

    International Nuclear Information System (INIS)

    Purpose: To investigate the plasma dynamics of 5 proinflammatory/fibrogenic cytokines, including interleukin-1beta (IL-1β), IL-6, IL-8, tumor necrosis factor alpha (TNF-α), and transforming growth factor beta1 (TGF-β1) to ascertain their value in predicting radiation-induced lung toxicity (RILT), both individually and in combination with physical dosimetric parameters. Methods and Materials: Treatments of patients receiving definitive conventionally fractionated radiation therapy (RT) on clinical trial for inoperable stages I-III lung cancer were prospectively evaluated. Circulating cytokine levels were measured prior to and at weeks 2 and 4 during RT. The primary endpoint was symptomatic RILT, defined as grade 2 and higher radiation pneumonitis or symptomatic pulmonary fibrosis. Minimum follow-up was 18 months. Results: Of 58 eligible patients, 10 (17.2%) patients developed RILT. Lower pretreatment IL-8 levels were significantly correlated with development of RILT, while radiation-induced elevations of TGF-ß1 were weakly correlated with RILT. Significant correlations were not found for any of the remaining 3 cytokines or for any clinical or dosimetric parameters. Using receiver operator characteristic curves for predictive risk assessment modeling, we found both individual cytokines and dosimetric parameters were poor independent predictors of RILT. However, combining IL-8, TGF-ß1, and mean lung dose into a single model yielded an improved predictive ability (P<.001) compared to either variable alone. Conclusions: Combining inflammatory cytokines with physical dosimetric factors may provide a more accurate model for RILT prediction. Future study with a larger number of cases and events is needed to validate such findings.

  9. Ell3 stimulates proliferation, drug resistance, and cancer stem cell properties of breast cancer cells via a MEK/ERK-dependent signaling pathway

    International Nuclear Information System (INIS)

    Highlights: •Ell3 enhances proliferation and drug resistance of breast cancer cell lines. •Ell3 is related to the cancer stem cell characteristics of breast cancer cell lines. •Ell3 enhances oncogenicity of breast cancer through the ERK1/2 signaling pathway. -- Abstract: Ell3 is a RNA polymerase II transcription elongation factor that is enriched in testis. The C-terminal domain of Ell3 shows strong similarities to that of Ell (eleven−nineteen lysine-rich leukemia gene), which acts as a negative regulator of p53 and regulates cell proliferation and survival. Recent studies in our laboratory showed that Ell3 induces the differentiation of mouse embryonic stem cells by protecting differentiating cells from apoptosis via the promotion of p53 degradation. In this study, we evaluated the function of Ell3 in breast cancer cell lines. MCF-7 cell lines overexpressing Ell3 were used to examine cell proliferation and cancer stem cell properties. Ectopic expression of Ell3 in breast cancer cell lines induces proliferation and 5-FU resistance. In addition, Ell3 expression increases the cancer stem cell population, which is characterized by CD44 (+) or ALDH1 (+) cells. Mammosphere-forming potential and migration ability were also increased upon Ell3 expression in breast cancer cell lines. Through biochemical and molecular biological analyses, we showed that Ell3 regulates proliferation, cancer stem cell properties and drug resistance in breast cancer cell lines partly through the MEK−extracellular signal-regulated kinase signaling pathway. Murine xenograft experiments showed that Ell3 expression promotes tumorigenesis in vivo. These results suggest that Ell3 may play a critical role in promoting oncogenesis in breast cancer by regulating cell proliferation and cancer stem cell properties via the ERK1/2 signaling pathway

  10. Ell3 stimulates proliferation, drug resistance, and cancer stem cell properties of breast cancer cells via a MEK/ERK-dependent signaling pathway

    Energy Technology Data Exchange (ETDEWEB)

    Ahn, Hee-Jin [Department of Biomedical Science, College of Life Science, CHA University, Seoul (Korea, Republic of); Kim, Gwangil [Department of Pathology, CHA Bundang Medical Center, CHA University, Seoul (Korea, Republic of); Park, Kyung-Soon, E-mail: kspark@cha.ac.kr [Department of Biomedical Science, College of Life Science, CHA University, Seoul (Korea, Republic of)

    2013-08-09

    Highlights: •Ell3 enhances proliferation and drug resistance of breast cancer cell lines. •Ell3 is related to the cancer stem cell characteristics of breast cancer cell lines. •Ell3 enhances oncogenicity of breast cancer through the ERK1/2 signaling pathway. -- Abstract: Ell3 is a RNA polymerase II transcription elongation factor that is enriched in testis. The C-terminal domain of Ell3 shows strong similarities to that of Ell (eleven−nineteen lysine-rich leukemia gene), which acts as a negative regulator of p53 and regulates cell proliferation and survival. Recent studies in our laboratory showed that Ell3 induces the differentiation of mouse embryonic stem cells by protecting differentiating cells from apoptosis via the promotion of p53 degradation. In this study, we evaluated the function of Ell3 in breast cancer cell lines. MCF-7 cell lines overexpressing Ell3 were used to examine cell proliferation and cancer stem cell properties. Ectopic expression of Ell3 in breast cancer cell lines induces proliferation and 5-FU resistance. In addition, Ell3 expression increases the cancer stem cell population, which is characterized by CD44 (+) or ALDH1 (+) cells. Mammosphere-forming potential and migration ability were also increased upon Ell3 expression in breast cancer cell lines. Through biochemical and molecular biological analyses, we showed that Ell3 regulates proliferation, cancer stem cell properties and drug resistance in breast cancer cell lines partly through the MEK−extracellular signal-regulated kinase signaling pathway. Murine xenograft experiments showed that Ell3 expression promotes tumorigenesis in vivo. These results suggest that Ell3 may play a critical role in promoting oncogenesis in breast cancer by regulating cell proliferation and cancer stem cell properties via the ERK1/2 signaling pathway.

  11. Cancer stem cells, tumor dormancy, and metastasis

    OpenAIRE

    EmilyChen

    2012-01-01

    Tumor cells can persist undetectably for an extended period of time in primary tumors and in disseminated cancer cells. Very little is known about why and how these tumors persist for extended periods of time and then evolve to malignancy. The discovery of cancer stem cells (CSCs) in human tumors challenges our current understanding of tumor recurrence, drug resistance, and metastasis, and opens up new research directions on how cancer cells are capable of switching from dormancy to malignanc...

  12. Cancer stem cells and brain tumors

    OpenAIRE

    Pérez Castillo, Ana; Aguilar Morante, Diana; Morales-García, José A.; Dorado, Jorge

    2008-01-01

    Besides the role of normal stem cells in organogenesis, cancer stem cells are thought to be crucial for tumorigenesis. Most current research on human tumors is focused on molecular and cellular analysis of the bulk tumor mass. However, evidence in leukemia and, more recently, in solid tumors suggests that the tumor cell population is heterogeneous. In recent years, several groups have described the existence of a cancer stem cell population in different brain tumors. These neural cancer stem ...

  13. Cancer Immunotherapy Using Engineered Hematopoietic Stem Cells

    OpenAIRE

    Gschweng, Eric Hans

    2015-01-01

    Engineering the immune system against cancer ideally provides surgical precision against the antigen bearing target cell while avoiding the systemic, off-target toxicity of chemotherapy. Successful treatment of patients in the clinic has been achieved by the expression of anti-cancer T-cell receptors (TCR) and chimeric antigen receptors (CAR) in T cells followed by infusion of these cells into cancer patients. Unfortunately, while many patients initially respond showing anti-tumor efficacy, t...

  14. Mitotic Control of Cancer Stem Cells

    OpenAIRE

    Venere, Monica; Miller, Tyler E.; Rich, Jeremy N.

    2013-01-01

    Cancer stem cells are self-renewing, tumorigenic cells at the apex of tumor hierarchies, and postulated to be quiescent in many tumor types. This issue of Cancer Discovery highlights a study that links the presentation of kinetochores within mitosis to an essential requirement for BUB1B/BubR1, broadening our understanding of the cell-cycle machinery in cancer stem cells.

  15. State of the art biological therapies in pancreatic cancer

    Institute of Scientific and Technical Information of China (English)

    2016-01-01

    Pancreatic ductal adenocarcinoma (PDAC) is one ofthe most lethal malignancies with a five-year survivalrate of approximately 5%. Several target agents havebeen tested in PDAC, but almost all have failed todemonstrate efficacy in late phase clinical trials, despitethe better understanding of PDAC molecular biologygenerated by large cancer sequencing initiatives in thepast decade. Eroltinib (a small-molecule tyrosine-kinaseinhibitor of epidermal growth factor receptor) plusgemcitabine is the only schedule with a biological agentapproved for advanced pancreatic cancer, but it hasresulted in a very modest survival benefit in unselectedpatients. In our work, we report a summary of the mainclinical trials (closed and ongoing) that refer to biologicaltherapy evaluation in pancreatic cancer treatment.

  16. Cell Biology Apps for Apple Devices

    OpenAIRE

    Stark, Louisa A.

    2012-01-01

    Apps for touch-pad devices hold promise for guiding and supporting learning. Students may use them in the classroom or on their own for didactic instruction, just-in-time learning, or review. Since Apple touch-pad devices (i.e., iPad and iPhone) have a substantial share of the touch-pad device market (Campbell, 2012), this Feature will explore cell biology apps available from the App Store. My review includes iPad and iPhone apps available in June 2012, but does not include courses, lectures,...

  17. Introduction to the cellular and molecular biology of cancer

    International Nuclear Information System (INIS)

    This collection of papers arose out of the needs of graduate students and research workers in highly specialised fields who had relatively little general knowledge of cancer. The introduction describes the pathology and natural history of the disease, with special reference to leukemia. Further chapters discuss susceptibility to the disease, cell behaviour (radiosensitivity, cell cycling, development of drug resistance etc), chemical and radiation carcinogenesis, the role of growth factors and hormones in cancer, diagnosis and local treatment, the role of monoclonal antibodies, and general epidemiology and risk factors. General glossary and further reading lists. (U.K.)

  18. RNA interference targeting raptor inhibits proliferation of gastric cancer cells

    International Nuclear Information System (INIS)

    Mammalian target of rapamycin complex 1 (mTORC1) is dysregulated in gastric cancer. The biologic function of mTORC1 in gastric carcinogenesis is unclear. Here, we demonstrate that disruption of mTORC1 function by RNA interference-mediated downregulation of raptor substantially inhibited gastric cancer cell proliferation through induction of G0/G1-phase cell cycle arrest. The anti-proliferative effect was accompanied by concomitant downregulation of activator protein-1 and upregulation of Smad2/3 transcriptional activities. In addition, the expression of cyclin D3 and p21Waf1, which stabilizes cyclin D/cdk4 complex for G1-S transition, was reduced by raptor knockdown. In conclusion, disruption of mTORC1 inhibits gastric cancer cell proliferation through multiple pathways. This discovery may have an implication in the application of mTORC1-directed therapy for the treatment of gastric cancer.

  19. Interleukin-22 Is Frequently Expressed in Small- and Large-Cell Lung Cancer and Promotes Growth in Chemotherapy-Resistant Cancer Cells

    OpenAIRE

    Kobold, Sebastian; Völk, Stefanie; Clauditz, Till; Küpper, Natascha Jennifer; Minner, Sarah; Tufman, Amanda; Düwell, Peter; Lindner, Michael; Koch, Ina; Heidegger, Simon; Rothenfußer, Simon; Schnurr, Max; Huber, Rudolf Maria; Wilczak, Waldemar; Endres, Stefan

    2013-01-01

    Introduction: In lung cancer, interleukin-22 (IL-22) expression within primary tissue has been demonstrated, but the frequency and the functional consequence of IL-22 signaling have not been addressed. This study aims at analyzing the cellular effects of IL-22 on lung carcinoma cell lines and the prognostic impact of IL-22 tissue expression in lung cancer patients. Methods: Biological effects of IL-22 signaling were investigated in seven lung cancer cell lines by Western blot, flow cytometry,...

  20. Targeting cancer stem cells: emerging role of Nanog transcription factor

    Directory of Open Access Journals (Sweden)

    Wang ML

    2013-09-01

    Full Text Available Mong-Lien Wang,1 Shih-Hwa Chiou,2,3 Cheng-Wen Wu1,4–61Institute of Biochemistry and Molecular Biology, 2Institute of Pharmacology, National Yang Ming University, Taipei, Taiwan; 3Department of Medical Research and Education, Taipei Veterans General Hospital, Taipei, Taiwan; 4Institute of Microbiology and Immunology, 5Institute of Clinical Medicine, National Yang Ming University, Taipei, Taiwan; 6Institute of Biomedical Science, Academia Sinica, Taipei, TaiwanAbstract: The involvement of stemness factors in cancer initiation and progression has drawn much attention recently, especially after the finding that introducing four stemness factors in somatic cells is able to reprogram the cells back to an embryonic stem cell-like state. Following accumulating data revealing abnormal elevated expression levels of key stemness factors, like Nanog, Oct4, and Sox2, in several types of cancer stem cells; the importance and therapeutic potential of targeting these stemness regulators in cancers has turned to research focus. Nanog determines cell fate in both embryonic and cancer stem cells; activating Nanog at an inappropriate time would result in cancer stem cells rather than normal pluripotent stem cells or differentiated somatic cells. Upregulated Nanog is correlated with poor survival outcome of patients with various types of cancer. The discoveries of downstream regulatory pathways directly or indirectly mediated by Nanog indicate that Nanog regulates several aspects of cancer development such as tumor cell proliferation, self-renewal, motility, epithelial-mesenchymal transition, immune evasion, and drug-resistance, which are all defined features for cancer stem cells. The current review paper illustrates the central role of Nanog in the regulatory networks of cancer malignant development and stemness acquirement, as well as in the communication between cancer cells and the surrounding stroma. Though a more defined model is needed to test the

  1. Biological effects of heavy ion and X-ray irradiation on lung cancer cells A549%重离子与X射线照射肺癌细胞A549的生物学效应比较

    Institute of Scientific and Technical Information of China (English)

    杨立娜; 冉俊涛; 张红; 刘圆圆; 孙超; 张秋宁; 王新宇; 王小虎

    2014-01-01

    Objective To compare the effects of carbon heavy ion and X-ray irradiation on survival fraction,cell cycle,cell apoptosis and expression of DNA-PKcs of A549 lung cancer cells.Methods A549 cells were irradiated by carbon heavy ion and X-ray.Cell survival fraction,cell cycle and apoptosis were analyzed by clonogenic formation assay,flow cytometry and Hoechst 33258 staining,respectively.Real time-PCR was performed to detect the expressions of DNA-PKcs and H2AX mRNA.Results Lower cell survival fraction,more G2/M phase arrest and higher apoptosis rate were detected in the A549 cells exposed to carbon heavy ion than X-ray(t =4.77,14.53,14.54,P < 0.05).Expression of DNA-PKcs was up-regulated after irradiation to carbon heavy ion and X-ray(t =10.91,5.05,P < 0.05).Conclusions Both heavy ion and X-ray irradiations enhance the expression of DNA-PKcs,induce apoptosis through regulating cell cycle arrest,and hence reduce survival of A549 cells.Heavy ion irradiation shows more stronger biological effects than X-ray irradiation.%目的 比较碳重离子与X射线对肺癌细胞的生物学效应.方法 对A549细胞分别进行碳重离子和X射线照射,通过克隆形成实验检测照射后细胞存活情况;流式细胞术检测细胞周期分布;通过Hoechst 33258荧光染料对照射后固定的细胞进行染色,计算凋亡率;采用实时荧光定量PCR方法检测照射后48 h细胞内DNA依赖性蛋白激酶催化亚单位(DNA-PKcs)和H2AX的mRNA表达水平.结果 细胞存活曲线显示,碳重离子造成的细胞存活分数远低于X射线,并将细胞周期阻滞于G2/M期(t=4.77、14.53、14.54,P<0.05),导致大部分细胞进入凋亡途径.碳重离子与X射线辐照后DNA-PKcs的表达上调(t=10.91、5.05,P<0.05).结论 碳重离子照射对肺癌细胞造成生物学效应远高于X射线.

  2. S100A4 is frequently overexpressed in lung cancer cells and promotes cell growth and cell motility

    International Nuclear Information System (INIS)

    Highlights: • We observed frequent overexpression of S100A4 in lung cancer cell lines. • Knockdown of S100A4 suppressed proliferation in lung cancer cells. • Forced expression of S100A4 accelerated cell motility in lung cancer cells. • PRDM2 was found to be one of the downstream suppressed genes of S100A4. - Abstract: S100A4, a small calcium-binding protein belonging to the S100 protein family, is commonly overexpressed in a variety of tumor types and is widely accepted to associate with metastasis by regulating the motility and invasiveness of cancer cells. However, its biological role in lung carcinogenesis is largely unknown. In this study, we found that S100A4 was frequently overexpressed in lung cancer cells, irrespective of histological subtype. Then we performed knockdown and forced expression of S100A4 in lung cancer cell lines and found that specific knockdown of S100A4 effectively suppressed cell proliferation only in lung cancer cells with S100A4-overexpression; forced expression of S100A4 accelerated cell motility only in S100A4 low-expressing lung cancer cells. PRDM2 and VASH1, identified as novel upregulated genes by microarray after specific knockdown of S100A4 in pancreatic cancer, were also analyzed, and we found that PRDM2 was significantly upregulated after S100A4-knockdown in one of two analyzed S100A4-overexpressing lung cancer cells. Our present results suggest that S100A4 plays an important role in lung carcinogenesis by means of cell proliferation and motility by a pathway similar to that in pancreatic cancer

  3. S100A4 is frequently overexpressed in lung cancer cells and promotes cell growth and cell motility

    Energy Technology Data Exchange (ETDEWEB)

    Chen, Na; Sato, Daisuke; Saiki, Yuriko; Sunamura, Makoto; Fukushige, Shinichi; Horii, Akira, E-mail: horii@med.tohoku.ac.jp

    2014-05-09

    Highlights: • We observed frequent overexpression of S100A4 in lung cancer cell lines. • Knockdown of S100A4 suppressed proliferation in lung cancer cells. • Forced expression of S100A4 accelerated cell motility in lung cancer cells. • PRDM2 was found to be one of the downstream suppressed genes of S100A4. - Abstract: S100A4, a small calcium-binding protein belonging to the S100 protein family, is commonly overexpressed in a variety of tumor types and is widely accepted to associate with metastasis by regulating the motility and invasiveness of cancer cells. However, its biological role in lung carcinogenesis is largely unknown. In this study, we found that S100A4 was frequently overexpressed in lung cancer cells, irrespective of histological subtype. Then we performed knockdown and forced expression of S100A4 in lung cancer cell lines and found that specific knockdown of S100A4 effectively suppressed cell proliferation only in lung cancer cells with S100A4-overexpression; forced expression of S100A4 accelerated cell motility only in S100A4 low-expressing lung cancer cells. PRDM2 and VASH1, identified as novel upregulated genes by microarray after specific knockdown of S100A4 in pancreatic cancer, were also analyzed, and we found that PRDM2 was significantly upregulated after S100A4-knockdown in one of two analyzed S100A4-overexpressing lung cancer cells. Our present results suggest that S100A4 plays an important role in lung carcinogenesis by means of cell proliferation and motility by a pathway similar to that in pancreatic cancer.

  4. Low Temperature Plasma Kills SCaBER Cancer Cells

    Science.gov (United States)

    Barekzi, Nazir; van Way, Lucas; Laroussi, Mounir

    2013-09-01

    Squamous cell carcinoma of the bladder is a rare type of bladder cancer that forms as a result of chronic irritation of the epithelial lining of the bladder. The cell line used in this study is SCaBER (ATCC® HTB-3™) derived from squamous cell carcinoma of the human urinary bladder. Current treatments of bladder cancer include surgery, radiation and chemotherapy. However, the cost of these treatments, the potential toxicity of the chemotherapeutic agents and the systemic side-effects warrant an alternative to current cancer treatment. This paper represents preliminary studies to determine the effects of biologically tolerant plasma (BTP) on a cell line of human bladder cancer cells. Previous work by our group using the plasma pencil revealed the efficacy of BTP on leukemia cells suspended in solution. Based on these earlier findings we hypothesized that the plasma exposure would elicit a similar programmed cell death in the SCaBER cells. Trypan blue exclusion and MTT assays revealed the cell killing after exposure to BTP. Our study indicates that low temperature plasma generated by ionizing helium gas and the reactive species may be a suitable and safe alternative for cancer therapy.

  5. Biological effects of positron emitters in thyroid cell cultures

    International Nuclear Information System (INIS)

    Full text of publication follows. Aim: Today, the use of 124I- (β+, half-life 4.2 d) is an increasing field in positron emission tomography (PET). In principle, positrons deposit their energy in the surrounding material like electrons. Therefore, we investigated the biological effects of positron emitters in comparison to electrons in vitro. Materials and Methods: two different thyroid cell lines (Fischer Rat Thyroid Cell Line No. 5 (FRTL5) and human papillary thyroid cancer cell line BCPAP) were investigated in vitro. While FRTL5 has been described to express a high level of sodium iodine transporter (NIS), the NIS expression of BCPAP is known to be low. Parallel cultures were incubated with either 50 -400 kBq/ml 124I- (IBA) or 50-400 kBq/ml 131I- (GE Health care). Cell count and radioiodine uptake were determined 24 h to 144 h after isotope application. Additionally, 4',6-diamidino-2-phenylindole (DAPI) staining of ethanol fixed cells was performed and induced apoptosis was determined by morphological analysis of the cell nucleus (condensation, fragmentation) by fluorescence microscopy. Results: BCPAP showed no significant uptake (<0.1 % per one million cells). The proliferation of BCPAP cells was not significantly influenced by radioiodine incubation. The uptake of NIS-expressing FRTL5 cells ranged between 0.6 % and 4 % per one million cells, independently of the isotope. In FRTL5 cells the incubation with 131I- induced a significant dose-dependent inhibition of proliferation (p<0.05). The positron emitter 124I- induced analogue effects on proliferation compared to the electron emitter 131I- (30-40 % inhibition, 144 h incubation with 400 kBq/ml). In parallel, in FRTL5 cell lines an isotope-independent increase of morphological changes in the cell nuclei (up to 5 fold) could be determined. In contrast, no significant changes could be verified in BCPAP cell nuclei. Conclusions: As expected from the physical point of view, the biological effects of positrons

  6. Head and neck cancer stem cells.

    Science.gov (United States)

    Krishnamurthy, S; Nör, J E

    2012-04-01

    Most cancers contain a small sub-population of cells that are endowed with self-renewal, multipotency, and a unique potential for tumor initiation. These properties are considered hallmarks of cancer stem cells. Here, we provide an overview of the field of cancer stem cells with a focus on head and neck cancers. Cancer stem cells are located in the invasive fronts of head and neck squamous cell carcinomas (HNSCC) close to blood vessels (perivascular niche). Endothelial cell-initiated signaling events are critical for the survival and self-renewal of these stem cells. Markers such as aldehyde dehydrogenase (ALDH), CD133, and CD44 have been successfully used to identify highly tumorigenic cancer stem cells in HNSCC. This review briefly describes the orosphere assay, a method for in vitro culture of undifferentiated head and neck cancer stem cells under low attachment conditions. Notably, recent evidence suggests that cancer stem cells are exquisitely resistant to conventional therapy and are the "drivers" of local recurrence and metastatic spread. The emerging understanding of the role of cancer stem cells in the pathobiology of head and neck squamous cell carcinomas might have a profound impact on the treatment paradigms for this malignancy. PMID:21933937

  7. Implications of Stem Cells and Cancer Stem Cells for Understanding Fomation and Therapy of Cancer

    Institute of Scientific and Technical Information of China (English)

    Guanghui Li; Donglin Wang

    2005-01-01

    Most cancers are heterogeneous with respect to proliferation and differentiation. There is increasing evidence suggesting that only a minority of cancer cells, tumorigenic or tumor initiating cells, possess the capacity to proliferate extensively and form new hematopoietic cancer or solid tumors. Tumor initiating cells share characteristics required for normal stem cells. The dysregulation of self-renewal and proliferation of stem cells is a likely requirement for cancer development. This review formulates a model for the origin of cancer stem cells and regulating self-renewal which influences the way we study and treat cancer.

  8. Roles of maspin in biological behaviors of PC-3 prostate cancer cells%Maspin在前列腺癌PC-3细胞生物学行为中的作用

    Institute of Scientific and Technical Information of China (English)

    刘美琴; 周珺; 马亮; 国风

    2012-01-01

    AIM: To investigate the roles of maspin in the biological behaviors of prostate cancer cells. METHODS: Specific shRNA targeting maspin gene was designed. The plasmid targeting maspin gene was constructed and lentiviral expression system was used for transfection. qRT - PCR and Western blotting were performed to identify the stable maspin - shRNA - transfected PC - 3 cells. The expression of apoptosis - related genes was analyzed by qRT - PCR. Dynamic observation of cell growth and doubling time were conducted by an xCELLigence system. The cell death upon protea-some inhibitor treatment was determined by flow cytometry analysis. The expression levels of RelA and RelB were detected by Western blotting. RESULTS: The recombinant plasmid containing maspin - shRNA was successfully constructed. Limited dilution was performed to obtain monoclonal PC — 3 — siMaspin cells. The doubling time of PC — 3 — siMaspin cells was 26. 83 h while that of PC - 3 - control cells was 37. 95 h. The mRNA expression of bcl - 2 and A20 in PC - 3 - siMaspin cells was increased, while that of bax and bim was down - regulated. The cell death rates of PC - 3 - control cells and PC - 3 - siMaspin cells after treated with MG - 132 were 27. 1% ± 5. 6% and 7. 5% ± 2. 3% at 8 h , 24. 2% ± 3. 7% and 8.2%±2.5% at24h, and 28. 7%±3. 7% and7.6%±2.5% at 36 h after treatment, respectively. RelA expression was decreased in PC - 3 - control cells treated with MG - 132 while that in PC - 3 - siMaspin cells stayed unchanged. CONCLUSION: Maspin expression is increased in androgen - independent prostate cancer PC -3 cells. Maspin silencing significantly reduces the doubling time and accelerates the cell growth. Maspin silencing markedly reduces the sensitivity of PC -3 cells to proteasome inhibitor, which may be linked to the abolishment of RelA degradation.%目的:探讨maspin影响前列腺癌细胞生物学行为的作用机制.方法:设计并合成靶向maspin基因的特异性shRNA,构建靶

  9. Pinpoint attack on cancer cell with ions

    International Nuclear Information System (INIS)

    Microbeam technology is indispensable in bio-scientific research, for example the investigation of cell-to-cell communications such as bystander effects, the analysis of cellular spatial sensitivity, the interaction of damage caused by individual irradiation, cellular repair dynamics, and intra-cellular processes such as apoptosis. A single-ion hit technique using the heavy-ion microbeam is being developed at JAEA AVF cyclotron facility for elucidate of biofunctions. A heavy ion microbeam system was developed using a beam collimator with a 5 μm diameter hole. In the new system the microbeam spot was focused to 0.7 μm in diameter using focusing lenses. The PIXE analysis has been widely applied in the fields of biology and medicine. The use of micro-beams allows analyzing trace elements on the cellular level as well. In Air Micro-PIXE images the elemental distribution in the cell by scanning the micro-beams. Biological effects of heavy ion particle beams are markedly more potent, and the dose distribution of heavy ion particle beams is more concentrated than those of X-ray and gamma ray. Therefore, radiotherapy using heavy ion particle beams not only improves the prognosis of cancer patients, but significantly contributes to improvement of their quality of life by conserving the function and morphology of affected organs. A highly precise carbon ion microsurgery system will be developed to treat various small tumours based on the technique of microbeam formation. (author)

  10. Prostate Cancer Stem Cells: Viewing Signaling Cascades at a Finer Resolution.

    Science.gov (United States)

    Lin, Xiukun; Farooqi, Ammad Ahmad; Qureshi, Muhammad Zahid; Romero, Mirna Azalea; Tabassum, Sobia; Ismail, Muhammad

    2016-06-01

    It is becoming characteristically more understandable that within tumor cells, there lies a sub-population of tumor cells with "stem cell" like properties and remarkable ability of self-renewal. Many features of these self-renewing cells are comparable with normal stem cells and are termed as "cancer stem cells". Accumulating experimentally verified data has started to scratch the surface of spatio-temporally dysregulated intracellular signaling cascades in the biology of prostate cancer stem cells. We partition this multicomponent review into how different signaling cascades operate in cancer stem cells and how bioactive ingredients isolated from natural sources may modulate signaling network. PMID:26846602

  11. Open questions: The disrupted circuitry of the cancer cell

    Energy Technology Data Exchange (ETDEWEB)

    Wiley, H. S.

    2014-10-24

    Every new decade of biology brings with it a change in outlook driven by new technologies and fresh perspectives. Such is the case for cancer and how we consider the disease. The advent of molecular biology led to the identification of altered signaling molecules and 'oncogenes' that were proposed to drive uncontrolled cell proliferation. The rise of cell biology and new imaging and culturing technologies led to the idea that disruptions in the extracellular environment prime cells for transformation. In the current genomics era, cancer is most commonly seen as a genetic disorder where an unstable genome gives rise to a variety of different cell variants that are selected for proliferation and survival. All of these views are partially correct, of course, and are simply different ways of saying that genetic alterations in cancer cells result in a loss of growth homeostasis. They also take the view that molecular changes 'drive' a cell to grow uncontrollably, rather than tip the balance from one normal state (quiescence) to another (proliferation). Underlying this oversimplification is a profound ignorance of what controls homeostatic cell growth in the first place and how specific mutations impact it.

  12. Dendritic cell-based cancer immunotherapy for colorectal cancer

    OpenAIRE

    Kajihara, Mikio; Takakura, Kazuki; Kanai, Tomoya; Ito, Zensho; Saito, Keisuke; Takami, Shinichiro; Shimodaira, Shigetaka; Okamoto, Masato; Ohkusa, Toshifumi; Koido, Shigeo

    2016-01-01

    Colorectal cancer (CRC) is one of the most common cancers and a leading cause of cancer-related mortality worldwide. Although systemic therapy is the standard care for patients with recurrent or metastatic CRC, the prognosis is extremely poor. The optimal sequence of therapy remains unknown. Therefore, alternative strategies, such as immunotherapy, are needed for patients with advanced CRC. This review summarizes evidence from dendritic cell-based cancer immunotherapy strategies that are curr...

  13. Can molecular cell biology explain chromosome motions?

    Directory of Open Access Journals (Sweden)

    Gagliardi L

    2011-05-01

    Full Text Available Abstract Background Mitotic chromosome motions have recently been correlated with electrostatic forces, but a lingering "molecular cell biology" paradigm persists, proposing binding and release proteins or molecular geometries for force generation. Results Pole-facing kinetochore plates manifest positive charges and interact with negatively charged microtubule ends providing the motive force for poleward chromosome motions by classical electrostatics. This conceptual scheme explains dynamic tracking/coupling of kinetochores to microtubules and the simultaneous depolymerization of kinetochore microtubules as poleward force is generated. Conclusion We question here why cells would prefer complex molecular mechanisms to move chromosomes when direct electrostatic interactions between known bound charge distributions can accomplish the same task much more simply.

  14. The iSBTc/SITC primer on tumor immunology and biological therapy of cancer: a summary of the 2010 program

    Directory of Open Access Journals (Sweden)

    Urba Walter J

    2011-01-01

    Full Text Available Abstract The Society for Immunotherapy of Cancer, SITC (formerly the International Society for Biological Therapy of Cancer, iSBTc, aims to improve cancer patient outcomes by advancing the science, development and application of biological therapy and immunotherapy. The society and its educational programs have become premier destinations for interaction and innovation in the cancer biologics community. For over a decade, the society has offered the Primer on Tumor Immunology and Biological Therapy of Cancer™ in conjunction with its Annual Scientific Meeting. This report summarizes the 2010 Primer that took place October 1, 2010 in Washington, D.C. as part of the educational offerings associated with the society's 25th anniversary. The target audience was basic and clinical investigators from academia, industry and regulatory agencies, and included clinicians, post-doctoral fellows, students, and allied health professionals. Attendees were provided a review of basic immunology and educated on the current status and most recent advances in tumor immunology and clinical/translational caner immunology. Ten prominent investigators presented on the following topics: innate immunity and inflammation; an overview of adaptive immunity; dendritic cells; tumor microenvironment; regulatory immune cells; immune monitoring; cytokines in cancer immunotherapy; immune modulating antibodies; cancer vaccines; and adoptive T cell therapy. Presentation slides, a Primer webinar and additional program information are available online on the society's website.

  15. Targeted therapies in small cell lung cancer

    OpenAIRE

    LU, HONG-YANG; Wang, Xiao-Jia; Mao, Wei-Min

    2012-01-01

    Lung cancer is the leading cause of cancer-related mortality. Small cell lung cancer (SCLC) accounted for 12.95% of all lung cancer histological types in 2002. Despite trends toward modest improvement in survival, the outcome remains extremely poor. Chemotherapy is the cornerstone of treatment in SCLC. More than two-thirds of patients who succumb to lung cancer in the United States are over 65 years old. Elderly patients tolerate chemotherapy poorly and need novel therapeutic agents. Targeted...

  16. Ribonucleotide reductase and cancer: biological mechanisms and targeted therapies.

    Science.gov (United States)

    Aye, Y; Li, M; Long, M J C; Weiss, R S

    2015-04-16

    Accurate DNA replication and repair is essential for proper development, growth and tumor-free survival in all multicellular organisms. A key requirement for the maintenance of genomic integrity is the availability of adequate and balanced pools of deoxyribonucleoside triphosphates (dNTPs), the building blocks of DNA. Notably, dNTP pool alterations lead to genomic instability and have been linked to multiple human diseases, including mitochondrial disorders, susceptibility to viral infection and cancer. In this review, we discuss how a key regulator of dNTP biosynthesis in mammals, the enzyme ribonucleotide reductase (RNR), impacts cancer susceptibility and serves as a target for anti-cancer therapies. Because RNR-regulated dNTP production can influence DNA replication fidelity while also supporting genome-protecting DNA repair, RNR has complex and stage-specific roles in carcinogenesis. Nevertheless, cancer cells are dependent on RNR for de novo dNTP biosynthesis. Therefore, elevated RNR expression is a characteristic of many cancers, and an array of mechanistically distinct RNR inhibitors serve as effective agents for cancer treatment. The dNTP metabolism machinery, including RNR, has been exploited for therapeutic benefit for decades and remains an important target for cancer drug development. PMID:24909171

  17. Mitochondria, cholesterol and cancer cell metabolism.

    Science.gov (United States)

    Ribas, Vicent; García-Ruiz, Carmen; Fernández-Checa, José C

    2016-12-01

    Given the role of mitochondria in oxygen consumption, metabolism and cell death regulation, alterations in mitochondrial function or dysregulation of cell death pathways contribute to the genesis and progression of cancer. Cancer cells exhibit an array of metabolic transformations induced by mutations leading to gain-of-function of oncogenes and loss-of-function of tumor suppressor genes that include increased glucose consumption, reduced mitochondrial respiration, increased reactive oxygen species generation and cell death resistance, all of which ensure cancer progression. Cholesterol metabolism is disturbed in cancer cells and supports uncontrolled cell growth. In particular, the accumulation of cholesterol in mitochondria emerges as a molecular component that orchestrates some of these metabolic alterations in cancer cells by impairing mitochondrial function. As a consequence, mitochondrial cholesterol loading in cancer cells may contribute, in part, to the Warburg effect stimulating aerobic glycolysis to meet the energetic demand of proliferating cells, while protecting cancer cells against mitochondrial apoptosis due to changes in mitochondrial membrane dynamics. Further understanding the complexity in the metabolic alterations of cancer cells, mediated largely through alterations in mitochondrial function, may pave the way to identify more efficient strategies for cancer treatment involving the use of small molecules targeting mitochondria, cholesterol homeostasis/trafficking and specific metabolic pathways. PMID:27455839

  18. Emerging targets in pancreatic cancer: epithelial–mesenchymal transition and cancer stem cells

    Directory of Open Access Journals (Sweden)

    Castellanos JA

    2013-09-01

    Full Text Available Jason A Castellanos,1 Nipun B Merchant,1–3 Nagaraj S Nagathihalli1–31Department of Surgery, 2Department of Cancer Biology, Vanderbilt University School of Medicine, Nashville, TN, USA; 3Vanderbilt-Ingram Comprehensive Cancer Center, Nashville, TN, USAAbstract: Pancreatic ductal adenocarcinoma is one of the most aggressive solid malignancies and is characterized by poor response to current therapy and a dismal survival rate. Recent insights regarding the role of cancer stem cells (CSCs and epithelial–mesenchymal transition (EMT in tumorigenesis have brought further understanding to the field and have highlighted new therapeutic targets. CSCs are a distinct subset of cancer cells, with the ability to differentiate into other cell types and self-renew in order to fuel the maintenance of tumor amplification. Transition of a cancer cell from an EMT leads to increased migratory and invasive properties, and thus facilitates initiation of metastasis. EMT is regulated by a complex network of factors that includes cytokines, growth factors, aberrant signaling pathways, transcription factors, and the tumor microenvironment. There is emerging evidence that the EMT process may give rise to CSCs, or at least cells with stem cell-like properties. We review the key pathways involved in both of these processes, the biomarkers used to identify CSCs, and new therapeutic approaches targeting CSCs and EMT in pancreatic ductal adenocarcinoma.Keywords: epithelial-mesenchymal transition, cancer stem cells, tumor microenvironment, pancreatic ductal adenocarcinoma

  19. Cell of origin of lung cancer

    Directory of Open Access Journals (Sweden)

    Jennifer M Hanna

    2013-01-01

    Full Text Available Lung cancer is the leading cause of cancer deaths worldwide, and current therapies are disappointing. Elucidation of the cell(s of origin of lung cancer may lead to new therapeutics. In addition, the discovery of putative cancer-initiating cells with stem cell properties in solid tumors has emerged as an important area of cancer research that may explain the resistance of these tumors to currently available therapeutics. Progress in our understanding of normal tissue stem cells, tumor cell of origin, and cancer stem cells has been hampered by the heterogeneity of the disease, the lack of good in vivo transplantation models to assess stem cell behavior, and an overall incomplete understanding of the epithelial stem cell hierarchy. As such, a systematic computerized literature search of the MEDLINE database was used to identify articles discussing current knowledge about normal lung and lung cancer stem cells or progenitor cells. In this review, we discuss what is currently known about the role of cancer-initiating cells and normal stem cells in the development of lung tumors.

  20. Highly parallel identification of essential genes in cancer cells.

    Science.gov (United States)

    Luo, Biao; Cheung, Hiu Wing; Subramanian, Aravind; Sharifnia, Tanaz; Okamoto, Michael; Yang, Xiaoping; Hinkle, Greg; Boehm, Jesse S; Beroukhim, Rameen; Weir, Barbara A; Mermel, Craig; Barbie, David A; Awad, Tarif; Zhou, Xiaochuan; Nguyen, Tuyen; Piqani, Bruno; Li, Cheng; Golub, Todd R; Meyerson, Matthew; Hacohen, Nir; Hahn, William C; Lander, Eric S; Sabatini, David M; Root, David E

    2008-12-23

    More complete knowledge of the molecular mechanisms underlying cancer will improve prevention, diagnosis and treatment. Efforts such as The Cancer Genome Atlas are systematically characterizing the structural basis of cancer, by identifying the genomic mutations associated with each cancer type. A powerful complementary approach is to systematically characterize the functional basis of cancer, by identifying the genes essential for growth and related phenotypes in different cancer cells. Such information would be particularly valuable for identifying potential drug targets. Here, we report the development of an efficient, robust approach to perform genome-scale pooled shRNA screens for both positive and negative selection and its application to systematically identify cell essential genes in 12 cancer cell lines. By integrating these functional data with comprehensive genetic analyses of primary human tumors, we identified known and putative oncogenes such as EGFR, KRAS, MYC, BCR-ABL, MYB, CRKL, and CDK4 that are essential for cancer cell proliferation and also altered in human cancers. We further used this approach to identify genes involved in the response of cancer cells to tumoricidal agents and found 4 genes required for the response of CML cells to imatinib treatment: PTPN1, NF1, SMARCB1, and SMARCE1, and 5 regulators of the response to FAS activation, FAS, FADD, CASP8, ARID1A and CBX1. Broad application of this highly parallel genetic screening strategy will not only facilitate the rapid identification of genes that drive the malignant state and its response to therapeutics but will also enable the discovery of genes that participate in any biological process. PMID:19091943

  1. Accelerating cancer systems biology research through Semantic Web technology.

    Science.gov (United States)

    Wang, Zhihui; Sagotsky, Jonathan; Taylor, Thomas; Shironoshita, Patrick; Deisboeck, Thomas S

    2013-01-01

    Cancer systems biology is an interdisciplinary, rapidly expanding research field in which collaborations are a critical means to advance the field. Yet the prevalent database technologies often isolate data rather than making it easily accessible. The Semantic Web has the potential to help facilitate web-based collaborative cancer research by presenting data in a manner that is self-descriptive, human and machine readable, and easily sharable. We have created a semantically linked online Digital Model Repository (DMR) for storing, managing, executing, annotating, and sharing computational cancer models. Within the DMR, distributed, multidisciplinary, and inter-organizational teams can collaborate on projects, without forfeiting intellectual property. This is achieved by the introduction of a new stakeholder to the collaboration workflow, the institutional licensing officer, part of the Technology Transfer Office. Furthermore, the DMR has achieved silver level compatibility with the National Cancer Institute's caBIG, so users can interact with the DMR not only through a web browser but also through a semantically annotated and secure web service. We also discuss the technology behind the DMR leveraging the Semantic Web, ontologies, and grid computing to provide secure inter-institutional collaboration on cancer modeling projects, online grid-based execution of shared models, and the collaboration workflow protecting researchers' intellectual property. PMID:23188758

  2. CD24 negative lung cancer cells, possessing partial cancer stem cell properties, cannot be considered as cancer stem cells

    OpenAIRE

    Xu, Haineng; Mu, Jiasheng; Xiao, Jing; Wu, Xiangsong; Li, Maolan; Liu, Tianrun; Liu, Xinyuan

    2015-01-01

    Cancer stem cells (CSCs) play vital role in lung cancer progression, resistance, metastasis and relapse. Identifying lung CSCs makers for lung CSCs targeting researches are critical for lung cancer therapy. In this study, utilizing previous identified lung CSCs as model, we compared the expression of CD24, CD133 and CD44 between CSCs and non-stem cancer cells. Increased ratio of CD24- cells were found in CSCs. CD24- cells were then sorted by flow cytometry and their proliferative ability, che...

  3. Stage of breast cancer at diagnosis in New Zealand: impacts of socio-demographic factors, breast cancer screening and biology

    OpenAIRE

    Seneviratne, Sanjeewa; Lawrenson, Ross; Harvey, Vernon; Ramsaroop, Reena; Elwood, Mark; Scott, Nina; Sarfati, Diana; Campbell, Ian

    2016-01-01

    Background Examination of factors associated with late stage diagnosis of breast cancer is useful to identify areas which are amenable to intervention. This study analyses trends in cancer stage at diagnosis and impact of socio-demographic, cancer biological and screening characteristics on cancer stage in a population-based series of women with invasive breast cancer in New Zealand. Methods All women diagnosed with invasive breast cancer between 2000 and 2013 were identified from two regiona...

  4. Cell Wall Biology: Perspectives from Cell Wall Imaging

    Institute of Scientific and Technical Information of China (English)

    Kieran J.D.Lee; Susan E.Marcus; J.Paul Knox

    2011-01-01

    Polysaccharide-rich plant cell walls are important biomaterials that underpin plant growth,are major repositories for photosynthetically accumulated carbon,and,in addition,impact greatly on the human use of plants. Land plant cell walls contain in the region of a dozen major polysaccharide structures that are mostly encompassed by cellulose,hemicelluloses,and pectic polysaccharides. During the evolution of land plants,polysaccharide diversification appears to have largely involved structural elaboration and diversification within these polysaccharide groups. Cell wall chemistry is well advanced and a current phase of cell wall science is aimed at placing the complex polysaccharide chemistry in cellular contexts and developing a detailed understanding of cell wall biology. Imaging cell wall glycomes is a challenging area but recent developments in the establishment of cell wall molecular probe panels and their use in high throughput procedures are leading to rapid advances in the molecular understanding of the spatial heterogeneity of individual cell walls and also cell wall differences at taxonomic levels. The challenge now is to integrate this knowledge of cell wall heterogeneity with an understanding of the molecular and physiological mechanisms that underpin cell wall properties and functions.

  5. Mechanisms of Therapeutic Resistance in Cancer (Stem) Cells with Emphasis on Thyroid Cancer Cells

    OpenAIRE

    Hombach-Klonisch, Sabine; Natarajan, Suchitra; Thanasupawat, Thatchawan; Medapati, Manoj; PATHAK, ALOK; Ghavami, Saeid; Klonisch, Thomas

    2014-01-01

    The two main reasons for death of cancer patients, tumor recurrence and metastasis, are multi-stage cellular processes that involve increased cell plasticity and coincide with elevated resistance to anti-cancer treatments. Epithelial-to-mesenchymal transition (EMT) is a key contributor to metastasis in many cancer types, including thyroid cancer and is known to confer stem cell-like properties onto cancer cells. This review provides an overview of molecular mechanisms and factors known to con...

  6. Isolation and Identification of Cancer Stem-Like Cells from Murine Melanoma Cell Lines

    Institute of Scientific and Technical Information of China (English)

    Jun Dou; Kai Hu; Ning Gu; Meng Pan; Ping Wen; Yating Li; Quan Tang; Lili Chu; Fengshu Zhao; Chuilian Jiang; Weihua Hu

    2007-01-01

    In current study, cancer stem-like cells in the murine melanoma B16F10 cells were investigated. CD phenotypes of the B16F10 cells were analyzed by flow cytometry, and the specific CD phenotype cells from the B16F10 cells were isolated by MACS. Then we used colony formation assay in soft agar media, the cell growth assay in serum-free culture media as well as the tumorigenicity investigation of the specific CD phenotype cells in C57BL/6 mice,respectively, to identify cancer stem-like cells in the B16F10 cells. The results showed that the B16F10 cells could form spherical clones in serum-free culture media, and the rate of clonegenesis of CD133+, CD44+ and CD44+CD133+ cells was higher than that of CD133-, CD44- and CD44+CD133- cells in soft agar media, respectively.The tumorigenic potential of CD133+, CD44+, CD44+CD133+ cells and CD44+CD133+CD24+ cells was stronger than that of CD133-, CD44-, CD44+CD133- cells and CD44+CD133+CD24- cells in mice, respectively. In conclusion, the CD44+CD133+CD24+ cells have some biological properties of cancer stem-like cells or are highly similar to the characteristics of cancer stem cells (CSC). These results provide an important method for identifying cancer stem-like cells in B16F10 cells and for further cancer target therapy.

  7. Influence of TACE combined with radioactive seed radiotherapy on primary liver cancer patients’ malignant biological indicators

    Institute of Scientific and Technical Information of China (English)

    Yao Liu; Yu Wang; Guang-Yan Lei; Xiao-Hong Yan; Qiao Yang; Hai-Ping Zhu; Yi Geng

    2016-01-01

    Objective:To analyze the influence of TACE combined with radioactive seed radiotherapy on primary liver cancer patients’ malignant biological indicators.Methods:A total of 112 cases of primary liver cancer patients who received treatment in our hospital, Xijing Hospital and Tumor Hospital of Shaanxi Province were chosen as research subjects and divided into control group (TACE therapy alone) with 63 cases in it and observation group (TACE combined with radioactive seed radiotherapy) with 49 cases according to different treatment, and then the levels of malignant biological indicators after 2 months of treatment were compared between two groups.Results:Serum VEGF, FGF and MMP levels of observation group after treatment were significantly lower than those of control group; serum AFP-L3, GP73, Sb7-H3, AFU and CatS levels were significantly lower than those of control group; serum ICAM-1, ESM-1 and uPA levels were lower than those of control group.Conclusion: TACE combined with radioactive seed radiotherapy can effectively reduce primary liver cancer patients’ serum malignant biological indicator levels, decrease the degree of malignancy of cancer cells and slow disease progression, and is an ideal treatment.

  8. Biological Effects of Green Tea Capsule Supplementation in Pre-surgery Postmenopausal Breast Cancer Patients

    Directory of Open Access Journals (Sweden)

    StevenSYu

    2013-12-01

    Full Text Available Regular green tea intake has been associated with an inverse risk of breast cancer. There is compelling experimental evidence that green tea, particularly, epigallocatechin gallate, the most potent green tea catechin, possesses a range of anti-cancer properties. We conducted a pre-surgical study of green tea capsules versus no green tea in women with primary breast cancer to determine the effects of green tea supplementation on markers of biological response. Postmenopausal women with ductal carcinoma in situ (DCIS or stage I or II breast cancer took green tea capsules (940 mg per day for an average of 35 days prior to surgery (n=13 or received no green tea (n=18. Paired diagnostic core biopsy and surgical specimen samples were analyzed for cell proliferation (Ki-67, apoptosis (caspase 3 and angiogenesis (CD34 separately in benign and malignant cell components. There were no significant changes in caspase-3 and CD34 in the green tea and no green tea groups and there were no significant differences in the change in these markers between the two groups. However, Ki-67 levels declined in both benign and malignant cell components in the green tea group; the decline in Ki-67 positivity in malignant cells was not statistically significant (P=0.10 but was statistically significant in benign cells (P=0.007. Ki-67 levels in benign and malignant cells did not change significantly in the no green tea group. There was a statistically significant difference in the change in Ki-67 in benign cells (P=0.033 between the green tea and the no green tea groups. The trend of a consistent reduction in Ki-67 in both benign and malignant cells in the green tea group warrants further investigations in a larger study of breast cancer patients or high-risk women.

  9. Seeing Cells: Teaching the Visual/Verbal Rhetoric of Biology

    Science.gov (United States)

    Dinolfo, John; Heifferon, Barbara; Temesvari, Lesly A.

    2007-01-01

    This pilot study obtained baseline information on verbal and visual rhetorics to teach microscopy techniques to college biology majors. We presented cell images to students in cell biology and biology writing classes and then asked them to identify textual, verbal, and visual cues that support microscopy learning. Survey responses suggest that…

  10. Development of an autonomous biological cell manipulator with single-cell electroporation and visual servoing capabilities.

    Science.gov (United States)

    Sakaki, Kelly; Dechev, Nikolai; Burke, Robert D; Park, Edward J

    2009-08-01

    Studies of single cells via microscopy and microinjection are a key component in research on gene functions, cancer, stem cells, and reproductive technology. As biomedical experiments become more complex, there is an urgent need to use robotic systems to improve cell manipulation and microinjection processes. Automation of these tasks using machine vision and visual servoing creates significant benefits for biomedical laboratories, including repeatability of experiments, higher throughput, and improved cell viability. This paper presents the development of a new 5-DOF robotic manipulator, designed for manipulating and microinjecting single cells. This biological cell manipulator (BCM) is capable of autonomous scanning of a cell culture followed by autonomous injection of cells using single-cell electroporation (SCE). SCE does not require piercing the cell membrane, thereby keeping the cell membrane fully intact. The BCM features high-precision 3-DOF translational and 2-DOF rotational motion, and a second z-axis allowing top-down placement of a micropipette tip onto the cell membrane for SCE. As a technical demonstration, the autonomous visual servoing and microinjection capabilities of the single-cell manipulator are experimentally shown using sea urchin eggs. PMID:19605307

  11. Characterizing cancer cells with cancer stem cell-like features in 293T human embryonic kidney cells

    OpenAIRE

    Buchholz Thomas A; Lacerda Lara; Xu Wei; Robertson Fredika; Ueno Naoto T; Lucci Anthony; Landis Melissa D; Rodriguez Angel A; Li Li; Cohen Evan; Gao Hui; Krishnamurthy Savitri; Zhang Xiaomei; Debeb Bisrat G; Cristofanilli Massimo

    2010-01-01

    Abstract Background Since the first suggestion of prospectively identifiable cancer stem cells in solid tumors, efforts have been made to characterize reported cancer stem cell surrogates in existing cancer cell lines, and cell lines rich with these surrogates have been used to screen for cancer stem cell targeted agents. Although 293T cells were derived from human embryonic kidney, transplantation of these cells into the mammary fat pad yields aggressive tumors that self-renew as evidenced b...

  12. Simultaneous Expression of Cancer Stem Cell-Like Properties and Cancer-Associated Fibroblast-Like Properties in a Primary Culture of Breast Cancer Cells

    Energy Technology Data Exchange (ETDEWEB)

    Ishikawa, Mami; Inoue, Takahiro; Shirai, Takuma; Takamatsu, Kazuhiko; Kunihiro, Shiori; Ishii, Hirokazu [Frontiers of Innovative Research in Science and Technology (FIRST), Konan University, Kobe 650-0047 (Japan); Nishikata, Takahito, E-mail: nisikata@konan-u.ac.jp [Frontiers of Innovative Research in Science and Technology (FIRST), Konan University, Kobe 650-0047 (Japan); Frontier Institute for Biomolecular Engineering Research (FIBER), Konan University, Kobe 650-0047 (Japan)

    2014-07-31

    The importance of cancer-associated fibroblasts (CAFs) in cancer biology has been recently highlighted owing to their critical roles in cancer growth, progression, metastasis, and therapeutic resistance. We have previously established a primary culture of breast cancer cells, which showed epithelial-mesenchymal transition and cancer stem cell-like properties. In this study, we found that the primary culture also showed CAF-like properties. For example, hypoxia inducible factor 1α (HIF1A) and its downstream genes, nuclear factor-kappa B2 (NF-κB2) and BCL2/adenovirus E1B 19 kd-interacting protein 3 (BNIP3), and many enzymes involved in glycolysis, such as GAPDH, LDH, PGAM1, and PKM2, were highly overexpressed in the primary culture. Moreover, media conditioned with the primary culture cells enhanced the growth of breast cancer cells. Similar to previous CAF studies, this enhancement suggested to be occurred through fibroblast growth factor signaling. This MCKH primary culture cell, which showed simultaneous expression of tumorigenic and CAF properties, offers a unique experimental system for studying the biology of CAFs.

  13. Simultaneous Expression of Cancer Stem Cell-Like Properties and Cancer-Associated Fibroblast-Like Properties in a Primary Culture of Breast Cancer Cells

    International Nuclear Information System (INIS)

    The importance of cancer-associated fibroblasts (CAFs) in cancer biology has been recently highlighted owing to their critical roles in cancer growth, progression, metastasis, and therapeutic resistance. We have previously established a primary culture of breast cancer cells, which showed epithelial-mesenchymal transition and cancer stem cell-like properties. In this study, we found that the primary culture also showed CAF-like properties. For example, hypoxia inducible factor 1α (HIF1A) and its downstream genes, nuclear factor-kappa B2 (NF-κB2) and BCL2/adenovirus E1B 19 kd-interacting protein 3 (BNIP3), and many enzymes involved in glycolysis, such as GAPDH, LDH, PGAM1, and PKM2, were highly overexpressed in the primary culture. Moreover, media conditioned with the primary culture cells enhanced the growth of breast cancer cells. Similar to previous CAF studies, this enhancement suggested to be occurred through fibroblast growth factor signaling. This MCKH primary culture cell, which showed simultaneous expression of tumorigenic and CAF properties, offers a unique experimental system for studying the biology of CAFs

  14. Personalized Therapy of Small Cell Lung Cancer.

    Science.gov (United States)

    Schneider, Bryan J; Kalemkerian, Gregory P

    2016-01-01

    Small cell lung cancer (SCLC) is an aggressive, poorly differentiated neuroendocrine carcinoma with distinct clinical, pathological and molecular characteristics. Despite robust responses to initial chemotherapy and radiation, the prognosis of patients with SCLC remains poor with an overall 5-year survival rate of less than 10 %. Despite the fact that numerous molecularly targeted approaches have thus far failed to demonstrate clinical utility in SCLC, further advances will rely on better definition of the biological pathways that drive survival, proliferation and metastasis. Recent next-generation, molecular profiling studies have identified many new therapeutic targets in SCLC, as well as extreme genomic instability which explains the high degree of resistance. A wide variety of anti-angiogenic agents, growth factor inhibitors, pro-apoptotic agents, and epigenetic modulators have been evaluated in SCLC and many studies of these strategies are on-going. Perhaps the most promising approaches involve agents targeting cancer stem cell pathways and immunomodulatory drugs that interfere with the PD1 and CTLA-4 pathways. SCLC offers many barriers to the development of successful therapy, including limited tumor samples, inadequate preclinical models, high mutational burden, and aggressive tumor growth which impairs functional status and hampers enrollment on clinical trials. PMID:26703804

  15. Tritium and Autoradiography in Cell Biology

    International Nuclear Information System (INIS)

    Because tritium emits low energy beta radiation, it is the most useful isotope for high resolution autoradiography. The relative abundance of hydrogen in most biologically important substances combined with a relatively short half-life allows the labelling of cellular components at specific activities that can often be detected at intracellular dimensions by the use of nuclear emulsions. The cells are attached to glass by various cytological procedures and after fixation a -wet or fluid photographic emulsion is applied directly to the cell surface and allowed to dry. After exposure the emulsion is developed while still in contact with the biological specimen. The preparation, an autoradiogram, when viewed under the light microscope shows the cellular structures and the location of the isotope with a resolution of less than 1 pm. In this way the distribution of tritium-labelled deoxyribonucleic acid (DNA) of individual chromosomes has been traced through two to three cell divisions. These studies were made possible by the preparation of tritiated thymidine which is a highly selective label for DNA and is quickly depleted when the cell is removed from the environment containing the labelled thymidine. The technique has yielded information on the mechanism of DNA replication, structure and reproduction of chromosomes, kinetics of cell division and more recently on the patterns and time sequence in the reproduction of different chromosomes in the same nucleus and the different parts of a single chromosome. All chromosomes studied so far contain two functional sub-units of DNA which are distributed in a semi-conservative fashion during reproduction. The two sub-units are unlike in some structural sense that limits the type of exchanges that may occur among the four sub-units of a reproducing chromosome. Present evidence on sequences leads to the hypothesis that chromosomes reproduce in a genetically controlled sequence. Further evidence on the patterns and mechanism of

  16. Role of stem cells in cancer therapy and cancer stem cells: a review

    OpenAIRE

    Sales Kevin; Chaib Boussad; Sagar Jayesh; Winslet Marc; Seifalian Alexander

    2007-01-01

    Abstract For over 30 years, stem cells have been used in the replenishment of blood and immune systems damaged by the cancer cells or during treatment of cancer by chemotherapy or radiotherapy. Apart from their use in the immuno-reconstitution, the stem cells have been reported to contribute in the tissue regeneration and as delivery vehicles in the cancer treatments. The recent concept of 'cancer stem cells' has directed scientific communities towards a different wide new area of research fi...

  17. Treatment Options by Stage (Small Cell Lung Cancer)

    Science.gov (United States)

    ... Cancer Prevention Lung Cancer Screening Research Small Cell Lung Cancer Treatment (PDQ®)–Patient Version General Information About Small Cell Lung Cancer Go to Health Professional Version Key Points Small ...

  18. MET and Small-Cell Lung Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Gelsomino, Francesco, E-mail: francesco.gelsomino@istitutotumori.mi.it [Medical Oncology Unit 1, Medical Oncology Department, Fondazione IRCCS Istituto Nazionale Tumori, Via G. Venezian 1, 20133 Milano (Italy); Rossi, Giulio [Operative Unit of Pathology, Azienda Ospedaliero-Universitaria Policlinico, Via del Pozzo 71, 41124 Modena (Italy); Tiseo, Marcello [Medical Oncology Unit, Azienda Ospedaliero-Universitaria, Viale A. Gramsci 14, 43126 Parma (Italy)

    2014-10-13

    Small-cell lung cancer (SCLC) is one of the most aggressive lung tumors. The majority of patients with SCLC are diagnosed at an advanced stage. This tumor type is highly sensitive to chemo-radiation treatment, with very high response rates, but invariably relapses. At this time, treatment options are still limited and the prognosis of these patients is poor. A better knowledge of the molecular biology of SCLC allowed us to identify potential druggable targets. Among these, the MET/HGF axis seems to be one of the most aberrant signaling pathways involved in SCLC invasiveness and progression. In this review, we describe briefly all recent literature on the different molecular profiling in SCLC; in particular, we discuss the specific alterations involving c-MET gene and their implications as a potential target in SCLC.

  19. MET and Small-Cell Lung Cancer

    Directory of Open Access Journals (Sweden)

    Francesco Gelsomino

    2014-10-01

    Full Text Available Small-cell lung cancer (SCLC is one of the most aggressive lung tumors. The majority of patients with SCLC are diagnosed at an advanced stage. This tumor type is highly sensitive to chemo-radiation treatment, with very high response rates, but invariably relapses. At this time, treatment options are still limited and the prognosis of these patients is poor. A better knowledge of the molecular biology of SCLC allowed us to identify potential druggable targets. Among these, the MET/HGF axis seems to be one of the most aberrant signaling pathways involved in SCLC invasiveness and progression. In this review, we describe briefly all recent literature on the different molecular profiling in SCLC; in particular, we discuss the specific alterations involving c-MET gene and their implications as a potential target in SCLC.

  20. Gefitinib in Non Small Cell Lung Cancer

    Directory of Open Access Journals (Sweden)

    Raffaele Costanzo

    2011-01-01

    Full Text Available Gefitinib is an oral, reversible, tyrosine kinase inhibitor of epidermal growth factor receptor (EGFR that plays a key role in the biology of non small cell lung cancer (NSCLC. Phase I studies indicated that the recommended dose of gefitinib was 250 mg/day. Rash, diarrhea, and nausea were the most common adverse events. The positive results obtained in early phase 2 clinical trials with gefitinib were not confirmed in large phase 3 trials in unselected patients with advanced NSCLC. The subsequent discovery that the presence of somatic mutations in the kinase domain of EGFR strongly correlates with increased responsiveness to EGFR tyrosine kinase inhibitors prompted phase 2 and 3 trials with gefitinib in the first line-treatment of EGFR-mutated NSCLC. The results of these trials have demonstrated the efficacy of gefitinib that can be now considered as the standard first-line treatment of patients with advanced NSCLC harbouring activating EGFR mutations.

  1. Breast cancer stem-like cells and breast cancer therapy

    Institute of Scientific and Technical Information of China (English)

    Niansong Qian; Nobuko Kawaguchi-Sakita; Masakazu Toi

    2010-01-01

    @@ Until the early 1990s, human cancers were considered a morphologically heterogeneous population of cells. In 1997, Bonnet et al[1] demonstrated that a small population of leukemia cells was able to differentiate in vivo into leukemic blasts, indicating that the leukemic clone was organized as a hierarchy; this was subsequently denoted as cancer stem like cells (CSCs). CSCs are cancer cells that possess characteristics associated with normal stem cells and have the specific ability to give rise to all cell types found in a particular cancer. One reason for the failure of traditional anti tumor therapies might be their inability to eradicate CSCs. Therefore, therapies must identify and destroy CSCs in both primary and metastatic tumors.

  2. Cancer stem cells, cancer-initiating cells and methods for their detection.

    Science.gov (United States)

    Akbari-Birgani, Shiva; Paranjothy, Ted; Zuse, Anna; Janikowski, Tomasz; Cieślar-Pobuda, Artur; Likus, Wirginia; Urasińska, Elżbieta; Schweizer, Frank; Ghavami, Saeid; Klonisch, Thomas; Łos, Marek J

    2016-05-01

    The cancer stem cell (CSC) hypothesis considers CSCs as the main culprits of tumor initiation, propagation, metastasis and therapy failure. CSCs represent a minority subpopulation of cells within a tumor. Their detection, characterization and monitoring are crucial steps toward a better understanding of the biological roles of these special cells in the development and propagation of tumors which, in turn, improves clinical reasoning and treatment options. Nowadays, in vitro and in vivo assays are available that address the self-renewal and differentiation potential of CSCs, and advanced in vivo molecular imaging technology facilitates the detection and provides an unprecedented in vivo observation platform to study the behavior of CSCs in their natural environment. Here, we provide a brief overview of CSCs and describe modern cellular models and labeling techniques to study and trace CSCs. PMID:26976692

  3. Adipocyte activation of cancer stem cell signaling in breast cancer

    Institute of Scientific and Technical Information of China (English)

    Benjamin; Wolfson; Gabriel; Eades; Qun; Zhou

    2015-01-01

    Signaling within the tumor microenvironment has a critical role in cancer initiation and progression. Adipocytes, one of the major components of the breast microenvironment,have been shown to provide pro-tumorigenic signals that promote cancer cell proliferation and invasiveness in vitro and tumorigenicity in vivo. Adipocyte secreted factors such as leptin and interleukin-6(IL-6) have a paracrine effect on breast cancer cells. In adipocyte-adjacent breast cancer cells, the leptin and IL-6 signaling pathways activate janus kinase 2/signal transducer and activatorof transcription 5, promoting the epithelial-mesenchymal transition, and upregulating stemness regulators such as Notch, Wnt and the Sex determining region Y-box 2/octamer binding transcription factor 4/Nanog signaling axis. In this review we will summarize the major signaling pathways that regulate cancer stem cells in breast cancer and describe the effects that adipocyte secreted IL-6 and leptin have on breast cancer stem cell signaling. Finally we will introduce a new potential treatment paradigm of inhibiting the adipocyte-breast cancer cell signaling via targeting the IL-6 or leptin pathways.

  4. Confocal Raman imaging for cancer cell classification

    Science.gov (United States)

    Mathieu, Evelien; Van Dorpe, Pol; Stakenborg, Tim; Liu, Chengxun; Lagae, Liesbet

    2014-05-01

    We propose confocal Raman imaging as a label-free single cell characterization method that can be used as an alternative for conventional cell identification techniques that typically require labels, long incubation times and complex sample preparation. In this study it is investigated whether cancer and blood cells can be distinguished based on their Raman spectra. 2D Raman scans are recorded of 114 single cells, i.e. 60 breast (MCF-7), 5 cervix (HeLa) and 39 prostate (LNCaP) cancer cells and 10 monocytes (from healthy donors). For each cell an average spectrum is calculated and principal component analysis is performed on all average cell spectra. The main features of these principal components indicate that the information for cell identification based on Raman spectra mainly comes from the fatty acid composition in the cell. Based on the second and third principal component, blood cells could be distinguished from cancer cells; and prostate cancer cells could be distinguished from breast and cervix cancer cells. However, it was not possible to distinguish breast and cervix cancer cells. The results obtained in this study, demonstrate the potential of confocal Raman imaging for cell type classification and identification purposes.

  5. Cell biology apps for Apple devices.

    Science.gov (United States)

    Stark, Louisa A

    2012-01-01

    Apps for touch-pad devices hold promise for guiding and supporting learning. Students may use them in the classroom or on their own for didactic instruction, just-in-time learning, or review. Since Apple touch-pad devices (i.e., iPad and iPhone) have a substantial share of the touch-pad device market (Campbell, 2012), this Feature will explore cell biology apps available from the App Store. My review includes iPad and iPhone apps available in June 2012, but does not include courses, lectures, podcasts, audiobooks, texts, or other books. I rated each app on a five-point scale (1 star = lowest; 5 stars = highest) for educational and production values; I also provide an overall score. PMID:22949420

  6. Chemical kinetic mechanistic models to investigate cancer biology and impact cancer medicine

    Science.gov (United States)

    Stites, Edward C.

    2013-04-01

    Traditional experimental biology has provided a mechanistic understanding of cancer in which the malignancy develops through the acquisition of mutations that disrupt cellular processes. Several drugs developed to target such mutations have now demonstrated clinical value. These advances are unequivocal testaments to the value of traditional cellular and molecular biology. However, several features of cancer may limit the pace of progress that can be made with established experimental approaches alone. The mutated genes (and resultant mutant proteins) function within large biochemical networks. Biochemical networks typically have a large number of component molecules and are characterized by a large number of quantitative properties. Responses to a stimulus or perturbation are typically nonlinear and can display qualitative changes that depend upon the specific values of variable system properties. Features such as these can complicate the interpretation of experimental data and the formulation of logical hypotheses that drive further research. Mathematical models based upon the molecular reactions that define these networks combined with computational studies have the potential to deal with these obstacles and to enable currently available information to be more completely utilized. Many of the pressing problems in cancer biology and cancer medicine may benefit from a mathematical treatment. As work in this area advances, one can envision a future where such models may meaningfully contribute to the clinical management of cancer patients.

  7. Epigenetic targeting of ovarian cancer stem cells.

    Science.gov (United States)

    Wang, Yinu; Cardenas, Horacio; Fang, Fang; Condello, Salvatore; Taverna, Pietro; Segar, Matthew; Liu, Yunlong; Nephew, Kenneth P; Matei, Daniela

    2014-09-01

    Emerging results indicate that cancer stem-like cells contribute to chemoresistance and poor clinical outcomes in many cancers, including ovarian cancer. As epigenetic regulators play a major role in the control of normal stem cell differentiation, epigenetics may offer a useful arena to develop strategies to target cancer stem-like cells. Epigenetic aberrations, especially DNA methylation, silence tumor-suppressor and differentiation-associated genes that regulate the survival of ovarian cancer stem-like cells (OCSC). In this study, we tested the hypothesis that DNA-hypomethylating agents may be able to reset OCSC toward a differentiated phenotype by evaluating the effects of the new DNA methytransferase inhibitor SGI-110 on OCSC phenotype, as defined by expression of the cancer stem-like marker aldehyde dehydrogenase (ALDH). We demonstrated that ALDH(+) ovarian cancer cells possess multiple stem cell characteristics, were highly chemoresistant, and were enriched in xenografts residual after platinum therapy. Low-dose SGI-110 reduced the stem-like properties of ALDH(+) cells, including their tumor-initiating capacity, resensitized these OCSCs to platinum, and induced reexpression of differentiation-associated genes. Maintenance treatment with SGI-110 after carboplatin inhibited OCSC growth, causing global tumor hypomethylation and decreased tumor progression. Our work offers preclinical evidence that epigenome-targeting strategies have the potential to delay tumor progression by reprogramming residual cancer stem-like cells. Furthermore, the results suggest that SGI-110 might be administered in combination with platinum to prevent the development of recurrent and chemoresistant ovarian cancer. PMID:25035395

  8. Radiofrequency treatment alters cancer cell phenotype

    Science.gov (United States)

    Ware, Matthew J.; Tinger, Sophia; Colbert, Kevin L.; Corr, Stuart J.; Rees, Paul; Koshkina, Nadezhda; Curley, Steven; Summers, H. D.; Godin, Biana

    2015-07-01

    The importance of evaluating physical cues in cancer research is gradually being realized. Assessment of cancer cell physical appearance, or phenotype, may provide information on changes in cellular behavior, including migratory or communicative changes. These characteristics are intrinsically different between malignant and non-malignant cells and change in response to therapy or in the progression of the disease. Here, we report that pancreatic cancer cell phenotype was altered in response to a physical method for cancer therapy, a non-invasive radiofrequency (RF) treatment, which is currently being developed for human trials. We provide a battery of tests to explore these phenotype characteristics. Our data show that cell topography, morphology, motility, adhesion and division change as a result of the treatment. These may have consequences for tissue architecture, for diffusion of anti-cancer therapeutics and cancer cell susceptibility within the tumor. Clear phenotypical differences were observed between cancerous and normal cells in both their untreated states and in their response to RF therapy. We also report, for the first time, a transfer of microsized particles through tunneling nanotubes, which were produced by cancer cells in response to RF therapy. Additionally, we provide evidence that various sub-populations of cancer cells heterogeneously respond to RF treatment.

  9. Breathless cancer cells get fat on glutamine

    Institute of Scientific and Technical Information of China (English)

    Dimitrios Anastasiou; Lewis C Cantley

    2012-01-01

    Many cancer cells depend on glutamine as a fuel for proliferation,yet the mechanisms by which glutamine supports cancer metabolism are not fully understood.Two recent studies highlight an important role for glutamine in the synthesis of lipids and provide novel insights into how glutamine metabolism could be targeted for cancer therapy.

  10. Troglitazone reverses the multiple drug resistance phenotype in cancer cells

    Directory of Open Access Journals (Sweden)

    Gerald F Davies

    2009-03-01

    Full Text Available Gerald F Davies1, Bernhard HJ Juurlink2, Troy AA Harkness11Department of Anatomy and Cell Biology, College of Medicine, University of Saskatchewan, Saskatoon, Canada; 2College of Medicine, Alfaisal University, Riyadh, Kingdom of Saudi ArabiaAbstract: A major problem in treating cancer is the development of drug resistance. We previously demonstrated doxorubicin (DOX resistance in K562 human leukemia cells that was associated with upregulation of glyoxalase 1 (GLO-1 and histone H3 expression. The thiazolidinedione troglitazone (TRG downregulated GLO-1 expression and further upregulated histone H3 expression and post-translational modifications in these cells, leading to a regained sensitivity to DOX. Given the pleiotropic effects of epigenetic changes in cancer development, we hypothesized that TRG may downregulate the multiple drug resistance (MDR phenotype in a variety of cancer cells. To test this, MCF7 human breast cancer cells and K562 cells were cultured in the presence of low-dose DOX to establish DOX-resistant cell lines (K562/DOX and MCF7/DOX. The MDR phenotype was confirmed by Western blot analysis of the 170 kDa P-glycoprotein (Pgp drug efflux pump multiple drug resistance protein 1 (MDR-1, and the breast cancer resistance protein (BCRP. TRG markedly decreased expression of both MDR-1 and BCRP in these cells, resulting in sensitivity to DOX. Silencing of MDR-1 expression also sensitized MCF7/DOX cells to DOX. Use of the specific and irreversible peroxisome proliferator-activated receptor gamma (PPARγ inhibitor GW9662 in the nanomolar range not only demonstrated that the action of TRG on MCF/DOX was PPARγ-independent, but indicated that PPARγ may play a role in the MDR phenotype, which is antagonized by TRG. We conclude that TRG is potentially a useful adjunct therapy in chemoresistant cancers. Keywords: chemotherapy, doxorubicin, breast cancer resistance protein-1, multiple drug resistance, multiple drug resistance protein 1

  11. Cancer stem cell targeted therapy: progress amid controversies

    OpenAIRE

    Wang, Tao; Shigdar, Sarah; Gantier, Michael P.; Hou, Yingchun; Wang, Li; Li, Yong; Shamaileh, Hadi Al; Yin, Wang; ZHOU, SHU-FENG; Zhao, Xinhan; Duan, Wei

    2015-01-01

    Although cancer stem cells have been well characterized in numerous malignancies, the fundamental characteristics of this group of cells, however, have been challenged by some recent observations: cancer stem cells may not necessary to be rare within tumors; cancer stem cells and non-cancer stem cells may undergo reversible phenotypic changes; and the cancer stem cells phenotype can vary substantially between patients. Here the current status and progresses of cancer stem cells theory is illu...

  12. Modeling Cancer Metastasis using Global, Quantitative and Integrative Network Biology

    DEFF Research Database (Denmark)

    Schoof, Erwin; Erler, Janine

    understanding of molecular processes which are fundamental to tumorigenesis. In Article 1, we propose a novel framework for how cancer mutations can be studied by taking into account their effect at the protein network level. In Article 2, we demonstrate how global, quantitative data on phosphorylation dynamics...... can be generated using MS, and how this can be modeled using a computational framework for deciphering kinase-substrate dynamics. This framework is described in depth in Article 3, and covers the design of KinomeXplorer, which allows the prediction of kinases responsible for modulating observed...... phosphorylation dynamics in a given biological sample. In Chapter III, we move into Integrative Network Biology, where, by combining two fundamental technologies (MS & NGS), we can obtain more in-depth insights into the links between cellular phenotype and genotype. Article 4 describes the proof...

  13. Bridging cancer biology and the patients' needs with nanotechnology-based approaches.

    Science.gov (United States)

    Fonseca, Nuno A; Gregório, Ana C; Valério-Fernandes, Angela; Simões, Sérgio; Moreira, João N

    2014-06-01

    Cancer remains as stressful condition and a leading cause of death in the western world. Actual cornerstone treatments of cancer disease rest as an elusive alternative, offering limited efficacy with extensive secondary effects as a result of severe cytotoxic effects in healthy tissues. The advent of nanotechnology brought the promise to revolutionize many fields including oncology, proposing advanced systems for cancer treatment. Drug delivery systems rest among the most successful examples of nanotechnology. Throughout time they have been able to evolve as a function of an increased understanding from cancer biology and the tumor microenvironment. Marketing of Doxil® unleashed a remarkable impulse in the development of drug delivery systems. Since then, several nanocarriers have been introduced, with aspirations to overrule previous technologies, demonstrating increased therapeutic efficacy besides decreased toxicity. Spatial and temporal targeting to cancer cells has been explored, as well as the use of drug combinations co-encapsulated in the same particle as a mean to take advantage of synergistic interactions in vivo. Importantly, targeted delivery of siRNA for gene silencing therapy has made its way to the clinic for a "first in man" trial using lipid-polymeric-based particles. Focusing in state-of-the-art technology, this review will provide an insightful vision on nanotechnology-based strategies for cancer treatment, approaching them from a tumor biology-driven perspective, since their early EPR-based dawn to the ones that have truly the potential to address unmet medical needs in the field of oncology, upon targeting key cell subpopulations from the tumor microenvironment. PMID:24613464

  14. Tracking the 2015 Gastrointestinal Cancers Symposium: bridging cancer biology to clinical gastrointestinal oncology

    Directory of Open Access Journals (Sweden)

    Aprile G

    2015-05-01

    Full Text Available Giuseppe Aprile,1 Francesco Leone,2,3 Riccardo Giampieri,4 Mariaelena Casagrande,1 Donatella Marino,2,3 Luca Faloppi,4 Stefano Cascinu,4 Gianpiero Fasola,1 Mario Scartozzi5,6 1Department of Oncology, University and General Hospital, Udine, Italy; 2Medical Oncology Department, University of Turin, 3Institute for Cancer Research and Treatment, Candiolo, Turin, Italy; 4Medical Oncology Unit, Azienda Ospedaliero-Universitaria Ospedali Riuniti, Universita Politecnica delle Marche, Ancona, Italy; 5Medical Oncology Department, University of Cagliari, 6General Hospital, Cagliari, Italy Abstract: The 2015 Gastrointestinal Cancers Symposium (San Francisco, CA, USA; January 15–17 is the world-class conference co-sponsored by the American Society of Clinical Oncology, the American Society for Radiation Oncology, the American Gastroenterological Association Institute, and the Society of Surgical Oncology, in which the most innovative research results in digestive tract oncology are presented and discussed. In its twelfth edition, the meeting has provided new insights focusing on the underpinning biology and clinical management of gastrointestinal malignancies. More than 3,400 health care professionals gathered from all over the world to share their experiences on how to bridge the recent novelties in cancer biology with everyday medical practice. In this article, the authors report on the most significant advances, didactically moving on three different anatomic tracks: gastroesophageal malignancies, pancreatic and biliary cancers, and colorectal adenocarcinomas. Keywords: colorectal cancer, gastric cancer, ramucirumab, pembrolizumab, target therapy, onartuzumab, AMG 337

  15. The biology and function of exosomes in cancer.

    Science.gov (United States)

    Kalluri, Raghu

    2016-04-01

    Humans circulate quadrillions of exosomes at all times. Exosomes are a class of extracellular vesicles released by all cells, with a size range of 40-150 nm and a lipid bilayer membrane. Exosomes contain DNA, RNA, and proteins. Exosomes likely remove excess and/or unnecessary constituents from the cells, functioning like garbage bags, although their precise physiological role remains unknown. Additionally, exosomes may mediate specific cell-to-cell communication and activate signaling pathways in cells they fuse or interact with. Exosomes are detected in the tumor microenvironment, and emerging evidence suggests that they play a role in facilitating tumorigenesis by regulating angiogenesis, immunity, and metastasis. Circulating exosomes can be used as liquid biopsies and noninvasive biomarkers for early detection, diagnosis, and treatment of cancer patients. PMID:27035812

  16. Metabolomics Analyses of Cancer Cells in Controlled Microenvironments.

    Science.gov (United States)

    Gravel, Simon-Pierre; Avizonis, Daina; St-Pierre, Julie

    2016-01-01

    The tumor microenvironment is a complex and heterogeneous milieu in which cancer cells undergo metabolic reprogramming to fuel their growth. Cancer cell lines grown in vitro using traditional culture methods represent key experimental models to gain a mechanistic understanding of tumor biology. This protocol describes the use of gas chromatography-mass spectrometry (GC-MS) to assess metabolic changes in cancer cells grown under varied levels of oxygen and nutrients that may better mimic the tumor microenvironment. Intracellular metabolite changes, metabolite uptake and release, as well as stable isotope ((13)C) tracer analyses are done in a single experimental setup to provide an integrated understanding of metabolic adaptation. Overall, this chapter describes some essential tools and methods to perform comprehensive metabolomics analyses. PMID:27581029

  17. A triterpenoid from wild bitter gourd inhibits breast cancer cells

    Science.gov (United States)

    Bai, Li-Yuan; Chiu, Chang-Fang; Chu, Po-Chen; Lin, Wei-Yu; Chiu, Shih-Jiuan; Weng, Jing-Ru

    2016-03-01

    The antitumor activity of 3β,7β,25-trihydroxycucurbita-5,23(E)-dien-19-al (TCD), a triterpenoid isolated from wild bitter gourd, in breast cancer cells was investigated. TCD suppressed the proliferation of MCF-7 and MDA-MB-231 breast cancer cells with IC50 values at 72 h of 19 and 23 μM, respectively, via a PPARγ-independent manner. TCD induced cell apoptosis accompanied with pleiotrophic biological modulations including down-regulation of Akt-NF-κB signaling, up-regulation of p38 mitogen-activated protein kinase and p53, increased reactive oxygen species generation, inhibition of histone deacetylases protein expression, and cytoprotective autophagy. Together, these findings provided the translational value of TCD and wild bitter gourd as an antitumor agent for patients with breast cancer.

  18. Resveratrol induces apoptosis in pancreatic cancer cells

    Institute of Scientific and Technical Information of China (English)

    ZHOU Jia-hua; CHENG Hai-yan; YU Ze-qian; HE Dao-wei; PAN Zheng; YANG De-tong

    2011-01-01

    Background Pancreatic cancer is one of the most lethal human cancers with a very low survival rate of 5 years.Conventional cancer treatments including surgery, radiation, chemotherapy or combinations of these show little effect on this disease. Several proteins have been proved critical to the development and the progression of pancreatic cancer.The aim of this study was to investigate the effect of resveratrol on apoptosis in pancreatic cancer cells.Methods Several pancreatic cancer cell lines were screened by resveratrol, and its toxicity was tested by normal pancreatic cells. Western blotting was then performed to analyze the molecular mechanism of resveratrol induced apoptosis of pancreatic cancer cell lines.Results In the screened pancreatic cancer cell lines, capan-2 and colo357 showed high sensitivity to resveratrol induced apoptosis. Resveratrol exhibited insignificant toxicity to normal pancreatic cells. In resveratrol sensitive cells,capan-2 and colo357, the activation of caspase-3 was detected and showed significant caspase-3 activation upon resveratrol treatment; p53 and p21 were also detected up-regulated upon resveratrol treatment.Conclusion Resveratrol provides a promising anti-tumor stratagy to fight against pancreatic cancer.

  19. Cell Biology and Pathology of Podocytes

    Science.gov (United States)

    Greka, Anna; Mundel, Peter

    2013-01-01

    As an integral member of the filtration barrier in the kidney glomerulus, the podocyte is in a unique geographical position: It is exposed to chemical signals from the urinary space (Bowman’s capsule), it receives and transmits chemical and mechanical signals to/from the glomerular basement membrane upon which it elaborates, and it receives chemical and mechanical signals from the vascular space with which it also communicates. As with every cell, the ability of the podocyte to receive signals from the surrounding environment and to translate them to the intracellular milieu is dependent largely on molecules residing on the cell membrane. These molecules are the first-line soldiers in the ongoing battle to sense the environment, to respond to friendly signals, and to defend against injurious foes. In this review, we take a membrane biologist’s view of the podocyte, examining the many membrane receptors, channels, and other signaling molecules that have been implicated in podocyte biology. Although we attempt to be comprehensive, our goal is not to capture every membrane-mediated pathway but rather to emphasize that this approach may be fruitful in understanding the podocyte and its unique properties. PMID:22054238

  20. Markers of small cell lung cancer

    OpenAIRE

    Sharma SK; Taneja Tarvinder

    2004-01-01

    Abstract Lung cancer is the number one cause of cancer death; however, no specific serum biomarker is available till date for detection of early lung cancer. Despite good initial response to chemotherapy, small-cell lung cancer (SCLC) has a poor prognosis. Therefore, it is important to identify molecular markers that might influence survival and may serve as potential therapeutic targets. The review aims to summarize the current knowledge of serum biomarkers in SCLC to improve diagnostic effi...

  1. Cancer stem cell and its relevance to tumors resistance to radiotherapy

    International Nuclear Information System (INIS)

    The gradually accumulated information and knowledge regarding cancer stem cell or stem-like cancer cell greatly potentiated the research progression of radiation oncology and biology. In recent years, a series studies have uncovered that the cancer stem cell and cancer quiescent cell could be the major cells origin attributed to the radioresistance and recurrence of tumors in the course of radiotherapy. A rapid research progression has already been achieved respecting the radiosensitivity and related mechanisms of these two subsets of cancer cells, and which provides an idea strategy for development of the measures targeting tumor radioresistance. This paper reviewed and discussed the cellular basis and molecular mechanism of the tumor radioresistance from the aspects of cancer cells subsets and the radiobiological characteristics. (authors)

  2. Developmental biology: cell fate in the mammary gland

    Science.gov (United States)

    Most breast cancers have their origin in the luminal epithelial cells of the mammary gland. Defining how a master regulator controls the development of this cell lineage could provide important hints about why this should be. ...

  3. Extracellular Molecules Involved in Cancer Cell Invasion

    Energy Technology Data Exchange (ETDEWEB)

    Stivarou, Theodora; Patsavoudi, Evangelia, E-mail: epatsavoudi@pasteur.gr [Department of Biochemistry, Hellenic Pasteur Institute, Athens 11521 (Greece); Technological Educational Institute of Athens, Egaleo, Athens 12210 (Greece)

    2015-01-26

    Nowadays it is perfectly clear that understanding and eradicating cancer cell invasion and metastasis represent the crucial, definitive points in cancer therapeutics. During the last two decades there has been a great interest in the understanding of the extracellular molecular mechanisms involved in cancer cell invasion. In this review, we highlight the findings concerning these processes, focusing in particular on extracellular molecules, including extracellular matrix proteins and their receptors, growth factors and their receptors, matrix metalloproteinases and extracellular chaperones. We report the molecular mechanisms underlying the important contribution of this pool of molecules to the complex, multi-step phenomenon of cancer cell invasion.

  4. Voltage-Gated Ion Channels in Cancer Cell Proliferation

    Energy Technology Data Exchange (ETDEWEB)

    Rao, Vidhya R.; Perez-Neut, Mathew [Department of Molecular Pharmacology and Therapeutics, Loyola University Chicago 2160 S. 1st Ave, Maywood, IL 60153 (United States); Kaja, Simon [Department of Ophthalmology and Vision Research Center, School of Medicine, University of Missouri-Kansas City, 2411 Holmes St., Kansas City, MO 64108 (United States); Gentile, Saverio, E-mail: sagentile@luc.edu [Department of Molecular Pharmacology and Therapeutics, Loyola University Chicago 2160 S. 1st Ave, Maywood, IL 60153 (United States)

    2015-05-22

    Changes of the electrical charges across the surface cell membrane are absolutely necessary to maintain cellular homeostasis in physiological as well as in pathological conditions. The opening of ion channels alter the charge distribution across the surface membrane as they allow the diffusion of ions such as K{sup +}, Ca{sup ++}, Cl{sup −}, Na{sup +}. Traditionally, voltage-gated ion channels (VGIC) are known to play fundamental roles in controlling rapid bioelectrical signaling including action potential and/or contraction. However, several investigations have revealed that these classes of proteins can also contribute significantly to cell mitotic biochemical signaling, cell cycle progression, as well as cell volume regulation. All these functions are critically important for cancer cell proliferation. Interestingly, a variety of distinct VGICs are expressed in different cancer cell types, including metastasis but not in the tissues from which these tumors were generated. Given the increasing evidence suggesting that VGIC play a major role in cancer cell biology, in this review we discuss the role of distinct VGIC in cancer cell proliferation and possible therapeutic potential of VIGC pharmacological manipulation.

  5. Atypical protein kinase C zeta: potential player in cell survival and cell migration of ovarian cancer.

    Directory of Open Access Journals (Sweden)

    Kelly K Y Seto

    Full Text Available Ovarian cancer is one of the most aggressive gynaecological cancers, thus understanding the different biological pathways involved in ovarian cancer progression is important in identifying potential therapeutic targets for the disease. The aim of this study was to investigate the potential roles of Protein Kinase C Zeta (PRKCZ in ovarian cancer. The atypical protein kinase C isoform, PRKCZ, is involved in the control of various signalling processes including cell proliferation, cell survival, and cell motility, all of which are important for cancer development and progression. Herein, we observe a significant increase in cell survival upon PRKCZ over-expression in SKOV3 ovarian cancer cells; additionally, when the cells are treated with small interference RNA (siRNA targeting PRKCZ, the motility of SKOV3 cells decreased. Furthermore, we demonstrate that over-expression of PRKCZ results in gene and/or protein expression alterations of insulin-like growth factor 1 receptor (IGF1R and integrin beta 3 (ITGB3 in SKOV3 and OVCAR3 cells. Collectively, our study describes PRKCZ as a potential regulatory component of the IGF1R and ITGB3 pathways and suggests that it may play critical roles in ovarian tumourigenesis.

  6. Targeting prostate cancer stem cells for cancer therapy

    OpenAIRE

    Wang, Guocan; Wang, Zhiwei; Sarkar, Fazlul H; Wei, Wenyi

    2012-01-01

    Prostate cancer (PCa) is the most common malignant neoplasm in men and the second most frequent cause of cancer death for males in the United States. Recently, emerging evidence suggests that prostate cancer stem cells (CSCs) may play a critical role in the development and progression of PCa. Therefore, targeting prostate CSCs for the prevention of tumor progression and treatment of PCa could become a novel strategy for better treatment of patients diagnosed with PCa. In this review article, ...

  7. Preferential killing of cancer cells and activated human T cells using ZnO nanoparticles

    International Nuclear Information System (INIS)

    Nanoparticles are increasingly being recognized for their potential utility in biological applications including nanomedicine. Here we examine the response of normal human cells to ZnO nanoparticles under different signaling environments and compare it to the response of cancerous cells. ZnO nanoparticles exhibit a strong preferential ability to kill cancerous T cells (∼28-35 x) compared to normal cells. Interestingly, the activation state of the cell contributes toward nanoparticle toxicity, as resting T cells display a relative resistance while cells stimulated through the T cell receptor and CD28 costimulatory pathway show greater toxicity in direct relation to the level of activation. Mechanisms of toxicity appear to involve the generation of reactive oxygen species, with cancerous T cells producing higher inducible levels than normal T cells. In addition, nanoparticles were found to induce apoptosis and the inhibition of reactive oxygen species was found to be protective against nanoparticle induced cell death. The novel findings of cell selective toxicity, towards potential disease causing cells, indicate a potential utility of ZnO nanoparticles in the treatment of cancer and/or autoimmunity

  8. Preferential killing of cancer cells and activated human T cells using ZnO nanoparticles

    Energy Technology Data Exchange (ETDEWEB)

    Hanley, Cory; Layne, Janet; Feris, Kevin; Wingett, Denise [Department of Biological Sciences, Boise State University, Boise, ID 83725 (United States); Punnoose, Alex; Reddy, K M; Coombs, Isaac; Coombs, Andrew [Department of Physics, Boise State University, Boise, ID 83725 (United States)], E-mail: denisewingett@boisestate.edu

    2008-07-23

    Nanoparticles are increasingly being recognized for their potential utility in biological applications including nanomedicine. Here we examine the response of normal human cells to ZnO nanoparticles under different signaling environments and compare it to the response of cancerous cells. ZnO nanoparticles exhibit a strong preferential ability to kill cancerous T cells ({approx}28-35 x) compared to normal cells. Interestingly, the activation state of the cell contributes toward nanoparticle toxicity, as resting T cells display a relative resistance while cells stimulated through the T cell receptor and CD28 costimulatory pathway show greater toxicity in direct relation to the level of activation. Mechanisms of toxicity appear to involve the generation of reactive oxygen species, with cancerous T cells producing higher inducible levels than normal T cells. In addition, nanoparticles were found to induce apoptosis and the inhibition of reactive oxygen species was found to be protective against nanoparticle induced cell death. The novel findings of cell selective toxicity, towards potential disease causing cells, indicate a potential utility of ZnO nanoparticles in the treatment of cancer and/or autoimmunity.

  9. On the advent and necessity of molecular biology in the clinical management of lung cancer.

    Science.gov (United States)

    Rahbek Sørensen, H; Olsson, L

    1986-12-01

    The very rapidly expanding knowledge and technologies of molecular biology are reviewed with special reference to problems in the clinical management of lung cancer. Genetic events, tumor-associated antigens, production of murine and human monoclonal antibodies, culture of cell lines, intratumoral phenotypic diversity and squamous-lung-cancer-associated antigens are discussed and related to possible therapeutical approaches. A monoclonal antibody with high specificity for squamous cell lung cancer reacted positively in blood samples and tissue extracts in about 80%. Its use as a marker during follow-up after surgical treatment is demonstrated by examples. It is concluded that there will be limiting factors in the therapeutic use of monoclonal antibodies, such as intratumoral phenotypic diversity. Genetic analysis might be a method for selecting a high risk group of individuals in whom exposure to carcinogenic factors, such as cigarette smoking, would be fatal. Murine monoclonal antibodies can be used in vitro for screening, for histological examination and for prognostic studies. Human monoclonal antibodies should be used for in vivo purposes as well as for the screening of primary tumor and metastases for the therapy. To achieve usable results, the monoclonal antibodies should be raised against the cell membranes that, in particular, are expressed on the stem cells of the neoplastic cell population. PMID:2433792

  10. Carbon nanotubes: an emerging drug carrier for targeting cancer cells.

    Science.gov (United States)

    Rastogi, Vaibhav; Yadav, Pragya; Bhattacharya, Shiv Sankar; Mishra, Arun Kumar; Verma, Navneet; Verma, Anurag; Pandit, Jayanta Kumar

    2014-01-01

    During recent years carbon nanotubes (CNTs) have been attracted by many researchers as a drug delivery carrier. CNTs are the third allotropic form of carbon-fullerenes which were rolled into cylindrical tubes. To be integrated into the biological systems, CNTs can be chemically modified or functionalised with therapeutically active molecules by forming stable covalent bonds or supramolecular assemblies based on noncovalent interactions. Owing to their high carrying capacity, biocompatibility, and specificity to cells, various cancer cells have been explored with CNTs for evaluation of pharmacokinetic parameters, cell viability, cytotoxicty, and drug delivery in tumor cells. This review attempts to highlight all aspects of CNTs which render them as an effective anticancer drug carrier and imaging agent. Also the potential application of CNT in targeting metastatic cancer cells by entrapping biomolecules and anticancer drugs has been covered in this review. PMID:24872894

  11. Tracheal metastasis of small cell lung cancer

    OpenAIRE

    De, Sajal

    2009-01-01

    Endotracheal metastases of primary lung cancer are rare. Only one case of tracheal metastasis from small cell lung cancer has been reported in literature. Here, we report a rare case of a 45-year-old woman who was admitted for sudden-onset breathlessness with respiratory failure and required ventilatory support. Endotracheal growth was identified during bronchoscopy, and biopsy revealed endotracheal metastasis of small cell lung cancer.

  12. Repopulation of Ovarian Cancer Cells After Chemotherapy

    OpenAIRE

    Telleria, Carlos M.

    2013-01-01

    The high mortality rate caused by ovarian cancer has not changed for the past thirty years. Although most patients diagnosed with this disease respond to cytoreductive surgery and platinum-based chemotherapy and undergo remission, foci of cells almost always escape therapy, manage to survive, and acquire the capacity to repopulate the tumor. Repopulation of ovarian cancer cells that escape front-line chemotherapy, however, is a poorly understood phenomenon. Here I analyze cancer-initiating ce...

  13. Breast Cancer-Initiating Cells: Insights into Novel Treatment Strategies

    International Nuclear Information System (INIS)

    There is accumulating evidence that breast cancer may arise from mutated mammary stem/progenitor cells which have been termed breast cancer-initiating cells (BCIC). BCIC identified in clinical specimens based on membrane phenotype (CD44+/CD24−/low and/or CD133+ expression) or enzymatic activity of aldehyde dehydrogenase 1 (ALDH1+), have been demonstrated to have stem/progenitor cell properties, and are tumorigenic when injected in immunocompromized mice at very low concentrations. BCIC have also been isolated and in vitro propagated as non-adherent spheres of undifferentiated cells, and stem cell patterns have been recognized even in cancer cell lines. Recent findings indicate that aberrant regulation of self renewal is central to cancer stem cell biology. Alterations in genes involved in self-renewal pathways, such as Wnt, Notch, sonic hedgehog, PTEN and BMI, proved to play a role in breast cancer progression. Hence, targeting key elements mediating the self renewal of BCIC represents an attractive option, with a solid rationale, clearly identifiable molecular targets, and adequate knowledge of the involved pathways. Possible concerns are related to the poor knowledge of tolerance and efficacy of inhibiting self-renewal mechanisms, because the latter are key pathways for a variety of biological functions and it is unknown whether their interference would kill BCIC or simply temporarily stop them. Thus, efforts to develop BCIC-targeted therapies should not only be focused on interfering on self-renewal, but could seek to identify additional molecular targets, like those involved in regulating EMT-related pathways, in reversing the MDR phenotype, in inducing differentiation and controlling cell survival pathways

  14. Breast Cancer-Initiating Cells: Insights into Novel Treatment Strategies

    Directory of Open Access Journals (Sweden)

    Maria Grazia Daidone

    2011-03-01

    Full Text Available There is accumulating evidence that breast cancer may arise from mutated mammary stem/progenitor cells which have been termed breast cancer-initiating cells (BCIC. BCIC identified in clinical specimens based on membrane phenotype (CD44+/CD24−/low and/or CD133+ expression or enzymatic activity of aldehyde dehydrogenase 1 (ALDH1+, have been demonstrated to have stem/progenitor cell properties, and are tumorigenic when injected in immunocompromized mice at very low concentrations. BCIC have also been isolated and in vitro propagated as non-adherent spheres of undifferentiated cells, and stem cell patterns have been recognized even in cancer cell lines. Recent findings indicate that aberrant regulation of self renewal is central to cancer stem cell biology. Alterations in genes involved in self-renewal pathways, such as Wnt, Notch, sonic hedgehog, PTEN and BMI, proved to play a role in breast cancer progression. Hence, targeting key elements mediating the self renewal of BCIC represents an attractive option, with a solid rationale, clearly identifiable molecular targets, and adequate knowledge of the involved pathways. Possible concerns are related to the poor knowledge of tolerance and efficacy of inhibiting self-renewal mechanisms, because the latter are key pathways for a variety of biological functions and it is unknown whether their interference would kill BCIC or simply temporarily stop them. Thus, efforts to develop BCIC-targeted therapies should not only be focused on interfering on self-renewal, but could seek to identify additional molecular targets, like those involved in regulating EMT-related pathways, in reversing the MDR phenotype, in inducing differentiation and controlling cell survival pathways.

  15. Breast Cancer-Initiating Cells: Insights into Novel Treatment Strategies

    Energy Technology Data Exchange (ETDEWEB)

    Santilli, Guido; Binda, Mara; Zaffaroni, Nadia; Daidone, Maria Grazia, E-mail: mariagrazia.daidone@istitutotumori.mi.it [Department of Experimental Oncology and Molecular Medicine, Fondazione IRCCS-Istituto Nazionale dei Tumori, Via Amadeo 42, Milan 20133 (Italy)

    2011-03-16

    There is accumulating evidence that breast cancer may arise from mutated mammary stem/progenitor cells which have been termed breast cancer-initiating cells (BCIC). BCIC identified in clinical specimens based on membrane phenotype (CD44{sup +}/CD24{sup −/low} and/or CD133{sup +} expression) or enzymatic activity of aldehyde dehydrogenase 1 (ALDH1{sup +}), have been demonstrated to have stem/progenitor cell properties, and are tumorigenic when injected in immunocompromized mice at very low concentrations. BCIC have also been isolated and in vitro propagated as non-adherent spheres of undifferentiated cells, and stem cell patterns have been recognized even in cancer cell lines. Recent findings indicate that aberrant regulation of self renewal is central to cancer stem cell biology. Alterations in genes involved in self-renewal pathways, such as Wnt, Notch, sonic hedgehog, PTEN and BMI, proved to play a role in breast cancer progression. Hence, targeting key elements mediating the self renewal of BCIC represents an attractive option, with a solid rationale, clearly identifiable molecular targets, and adequate knowledge of the involved pathways. Possible concerns are related to the poor knowledge of tolerance and efficacy of inhibiting self-renewal mechanisms, because the latter are key pathways for a variety of biological functions and it is unknown whether their interference would kill BCIC or simply temporarily stop them. Thus, efforts to develop BCIC-targeted therapies should not only be focused on interfering on self-renewal, but could seek to identify additional molecular targets, like those involved in regulating EMT-related pathways, in reversing the MDR phenotype, in inducing differentiation and controlling cell survival pathways.

  16. Cell phones - do they cause cancer?

    Science.gov (United States)

    ... cancer URL of this page: //medlineplus.gov/ency/article/007151.htm Cell phones and cancer To use the sharing features ... adults. For this reason, some agencies and government organizations recommend that children avoid prolonged use of cell phones. REDUCING RISKS Although health problems related to ...

  17. Nonlinear Growth Kinetics of Breast Cancer Stem Cells: Implications for Cancer Stem Cell Targeted Therapy

    OpenAIRE

    Liu, Xinfeng; Johnson, Sara; Liu, Shou; Kanojia, Deepak; Yue, Wei; Singn, Udai; Wang, Qian; Wang, Qi; Nie, Qing; Chen, Hexin

    2013-01-01

    Cancer stem cells (CSCs) have been identified in primary breast cancer tissues and cell lines. The CSC population varies widely among cancerous tissues and cell lines, and is often associated with aggressive breast cancers. Despite of intensive research, how the CSC population is regulated within a tumor is still not well understood so far. In this paper, we present a mathematical model to explore the growth kinetics of CSC population both in vitro and in vivo. Our mathematical models and sup...

  18. Growth Analysis of Cancer Biology Research, 2000-2011

    Directory of Open Access Journals (Sweden)

    Keshava,

    2015-09-01

    Full Text Available Methods and Material: The PubMed database was used for retrieving data on 'cancer biology.' Articles were downloaded from the years 2000 to 2011. The articles were classified chronologically and transferred to a spreadsheet application for analysis of the data as per the objectives of the study. Statistical Method: To investigate the nature of growth of articles via exponential, linear, and logistics tests. Result: The year wise analysis of the growth of articles output shows that for the years 2000 to 2005 and later there is a sudden increase in output, during the years 2006 to 2007 and 2008 to 2011. The high productivity of articles during these years may be due to their significance in cancer biology literature, having received prominence in research. Conclusion: There is an obvious need for better compilations of statistics on numbers of publications in the years from 2000 to 2011 on various disciplines on a worldwide scale, for informed critical assessments of the amount of new knowledge contributed by these publications, and for enhancements and refinements of present Scientometric techniques (citation and publication counts, so that valid measures of knowledge growth may be obtained. Only then will Scientometrics be able to provide accurate, useful descriptions and predictions of knowledge growth.

  19. Chitosan Nanoparticles-Mediated Wild-Type p53 Gene Delivery for Cancer Gene Therapy: Improvement in Pharmaceutical & Biological Properties (Enhance in Loading, Release, Expression and Stability of P53 Plasmid and Induction of Apoptosis in Carcinoma Cell Line

    Directory of Open Access Journals (Sweden)

    Mehrdad Hamidi

    2008-05-01

    Full Text Available Efficient non-viral vectors for gene delivery based on chitosan polymer is dependent on a variety of factors, e.g. loading and lelease capacity, stability in biological system and complex size. This system may have low loading, release and stability capacity. Biodegradable and biocompatible nanoparticles formulated using a chitosan polymer has the potential for sustained and controlled gene delivery. Our hypothesis is that nanoparticles-mediated wild-type p53 gene delivery would result in sustained gene expression, and hence better efficacy with a therapeutic gene. In this study, we have determined the pharmaceutical and biological characterization of Chitosan nanoparticles containing wild-type p53. Nanoparticles containing plasmid were formulated using a microemulsion reverse micellar and ionic gelation techniques. In conclusion, chitosan nanoparticles- p53 complex gene delivery results in sustained and better antiproliferative activity, which could be therapeutically beneficial in cancer treatment.

  20. Enrichment and Function Research of Large Cell Lung Cancer Stem Cell-like Cells

    OpenAIRE

    Wenke YUE; JIAO, FENG; Liu, Bin; Jiacong YOU; Zhou, Qinghua

    2011-01-01

    Background and objective There are no universal method to recognize and screen for lung cancer stem cell markers and indicators. Commonly used methods are flow Cytometry and learning from other cancer stem cell sorting tags to sort lung cancer stem cells. But this method has low specificity screening, the workload is huge. In this study, Serum-free suspension culture was used to enrich lung cancer stem cells, and explore method for lung cancer stem cell screening. Methods Human large lung can...