Sample records for cancer cell biology

  1. Molecular Biology of Liver Cancer Stem Cells

    National Research Council Canada - National Science Library

    Oishi, Naoki; Yamashita, Taro; Kaneko, Shuichi


    .... The concept of cancer stem cells (CSCs) is based primarily on the clinical and experimental observations that indicate the existence of a subpopulation of cells with the capacity to self-renew and differentiate as well as show increased...

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


    Halliday A Idikio


    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...

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

    Directory of Open Access Journals (Sweden)

    Halliday A Idikio


    Full Text Available 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 the known attributes of cancer stem cells and their potential contribution to treatment response, and metastases. The integrated model of cancer classification presented here incorporates all morphology, cancer stem cell contributions, genetic, and functional attributes of cancer. Integrated cancer classification models could eliminate the unclassifiable cancers as used in current classifications. Future cancer treatment may be advanced by using an integrated model of cancer classification.

  4. Molecular biology of breast cancer stem cells: potential clinical applications. (United States)

    Nguyen, Nam P; Almeida, Fabio S; Chi, Alex; Nguyen, Ly M; Cohen, Deirdre; Karlsson, Ulf; Vinh-Hung, Vincent


    Breast cancer stem cells (CSC) have been postulated recently as responsible for failure of breast cancer treatment. The purpose of this study is to review breast CSCs molecular biology with respect to their mechanism of resistance to conventional therapy, and to develop treatment strategies that may improve survival of breast cancer patients. A literature search has identified in vitro and in vivo studies of breast CSCs. Breast CSCs overexpress breast cancer resistance protein (BCRP) which allows cancer cells to transport actively chemotherapy agents out of the cells. Radioresistance is modulated through activation of Wnt signaling pathway and overexpression of genes coding for glutathione. Lapatinib can selectively target HER-2 positive breast CSCs and improves disease-free survival in these patients. Metformin may target basal type breast CSCs. Parthenolide and oncolytic viruses are promising targeting agents for breast CSCs. Future clinical trials for breast cancer should include anti-cancer stem cells targeting agents in addition to conventional chemotherapy. Hypofractionation radiotherapy may be indicated for residual disease post chemotherapy. 2010 Elsevier Ltd. All rights reserved.

  5. Ovary and fimbrial stem cells: biology, niche and cancer origins. (United States)

    Ng, Annie; Barker, Nick


    The mammalian ovary is covered by a single-layered epithelium that undergoes rupture and remodelling following each ovulation. Although resident stem cells are presumed to be crucial for this cyclic regeneration, their identity and mode of action have been elusive. Surrogate stemness assays and in vivo fate-mapping studies using recently discovered stem cell markers have identified stem cell pools in the ovary and fimbria that ensure epithelial homeostasis. Recent findings provide insights into intrinsic mechanisms and local extrinsic cues that govern the function of ovarian and fimbrial stem cells. These discoveries have advanced our understanding of stem cell biology in the ovary and fimbria, and lay the foundations for evaluating the contribution of resident stem cells to the initiation and progression of human epithelial ovarian cancer.

  6. Integrins in mammary-stem-cell biology and breast-cancer progression – a role in cancer stem cells? (United States)

    Pontier, Stephanie M.; Muller, William J.


    Summary Cancer cells with stem cell-like properties (cancer stem cells) are believed to drive cancer and are associated with poor prognosis. Data from mouse models have demonstrated that integrins, the major cellular receptors for extracellular-matrix components, have essential roles both during cancer initiation and progression, and during cell differentiation in normal development. By presenting an overview of the role of integrins in stem-cell biology and in cancer progression, this Commentary aims to present evidence for a role of integrins in the biology of cancer stem cells. Given the recent interest in the role of integrins in breast-cancer initiation and progression, we focus on the role of the members of the integrin family and their coupled signaling pathways in mammary-gland development and tumorigenesis. PMID:19118213

  7. Integrins in mammary-stem-cell biology and breast-cancer progression--a role in cancer stem cells? (United States)

    Pontier, Stephanie M; Muller, William J


    Cancer cells with stem cell-like properties (cancer stem cells) are believed to drive cancer and are associated with poor prognosis. Data from mouse models have demonstrated that integrins, the major cellular receptors for extracellular-matrix components, have essential roles both during cancer initiation and progression, and during cell differentiation in normal development. By presenting an overview of the role of integrins in stem-cell biology and in cancer progression, this Commentary aims to present evidence for a role of integrins in the biology of cancer stem cells. Given the recent interest in the role of integrins in breast-cancer initiation and progression, we focus on the role of the members of the integrin family and their coupled signaling pathways in mammary-gland development and tumorigenesis.

  8. Competency development in antibody production in cancer cell biology

    Energy Technology Data Exchange (ETDEWEB)

    Park, M.S.


    This is the final report of a three-year, Laboratory Directed Research and Development (LDRD) project at Los Alamos National Laboratory (LANL). The main objective of this project was to develop a rapid recombinant antibody production technology. To achieve the objective, the authors employed (1) production of recombinant antigens that are important for cell cycle regulation and DNA repair, (2) immunization and specific selection of antibody-producing lymphocytes using the flow cytometry and magnetic bead capturing procedure, (3) construction of single chain antibody library, (4) development of recombinant vectors that target, express, and regulate the expression of intracellular antibodies, and (5) specific inhibition of tumor cell growth in tissue culture. The authors have accomplished (1) optimization of a selection procedure to isolate antigen-specific lymphocytes, (2) optimization of the construction of a single-chain antibody library, and (3) development of a new antibody expression vector for intracellular immunization. The future direction of this research is to continue to test the potential use of the intracellular immunization procedure as a tool to study functions of biological molecules and as an immuno-cancer therapy procedure to inhibit the growth of cancer cells.

  9. Cancer Stem Cells and Their Microenvironment: Biology and Therapeutic Implications

    Directory of Open Access Journals (Sweden)

    Eunice Yuen-Ting Lau


    Full Text Available Tumor consists of heterogeneous cancer cells including cancer stem cells (CSCs that can terminally differentiate into tumor bulk. Normal stem cells in normal organs regulate self-renewal within a stem cell niche. Likewise, accumulating evidence has also suggested that CSCs are maintained extrinsically within the tumor microenvironment, which includes both cellular and physical factors. Here, we review the significance of stromal cells, immune cells, extracellular matrix, tumor stiffness, and hypoxia in regulation of CSC plasticity and therapeutic resistance. With a better understanding of how CSC interacts with its niche, we are able to identify potential therapeutic targets for the development of more effective treatments against cancer.

  10. Mathematical models in cell biology and cancer chemotherapy

    CERN Document Server

    Eisen, Martin


    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. E. coli as a biological model for cancer cells (United States)

    Liao, David; Lambert, Guillaume; Austin, Robert


    Uninhibited growth and invasion of healthy tissue characterize cancer. We co-cultured two strains of E. coli bacteria in a microfabricated environment to model cancer. During starvation, growth-advantage-in-stationary-phase, or GASP, cells grew to a higher population than wild-type cells. GASP cells also displaced wild-type cells from nutrient-rich chambers. When we repeated the experiment with medium depleted by wild-type cells, the peak GASP population density increased 54%, and the ``invasion,'' or displacement of wild-type cells from nutrient-rich chambers, occurred 5 hours earlier. We mathematically modeled both this increase in GASP population and this acceleration of spatial invasion by assuming that GASP cells consume detritus secreted by wild-type cells. Our experimental and model results corroborate recent caution against using tumor starvation as a cancer therapy.

  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


    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. Cancer stem cells in hepatocellular carcinoma: Therapeutic implications based on stem cell biology. (United States)

    Chiba, Tetsuhiro; Iwama, Atsushi; Yokosuka, Osamu


    Hepatocellular carcinoma (HCC) is the sixth most common cancer and the third most frequent cause of cancer-related death worldwide. Despite advances in its diagnosis and treatment, the prognosis of patients with advanced HCC remains unfavorable. Recent advances in stem cell biology and associated technologies have enabled the identification of minor components of tumorigenic cells, termed cancer stem cells (CSC) or tumor-initiating cells, in cancers such as HCC. Furthermore, because CSC play a central role in tumor development, metastasis and recurrence, they are considered to be a therapeutic target in cancer treatment. Hepatic CSC have been successfully identified using functional and cell surface markers. The analysis of purified hepatic CSC has revealed the molecular machinery and signaling pathways involved in their maintenance. In addition, epigenetic transcriptional regulation has been shown to be important in the development and maintenance of CSC. Although inhibitors of CSC show promise as CSC-targeting drugs, novel therapeutic approaches for the eradication of CSC are yet to be established. In this review, we describe recent progress in hepatic CSC research and provide a perspective on the available therapeutic approaches based on stem cell biology. © 2015 The Japan Society of Hepatology.

  14. Molecular Cell Biology of Apoptosis and Necroptosis in Cancer. (United States)

    Dillon, Christopher P; Green, Douglas R

    Cell death is a major mechanism to eliminate cells in which DNA is damaged, organelles are stressed, or oncogenes are overexpressed, all events that would otherwise predispose cells to oncogenic transformation. The pathways that initiate and execute cell death are complex, genetically encoded, and subject to significant regulation. Consequently, while these pathways are often mutated in malignancy, there is considerable interest in inducing cell death in tumor cells as therapy. This chapter addresses our current understanding of molecular mechanisms contributing to two cell death pathways, apoptotic cell death and necroptosis, a regulated form of necrotic cell death. Apoptosis can be induced by a wide variety of signals, leading to protease activation that dismantles the cell. We discuss the physiological importance of each apoptosis pathway and summarize their known roles in cancer suppression and the current efforts at targeting each pathway therapeutically. The intricate mechanistic link between death receptor-mediated apoptosis and necroptosis is described, as well as the potential opportunities for utilizing necroptosis in the treatment of malignancy.

  15. Biological characteristics of side population cells in a self-established human ovarian cancer cell line. (United States)

    Wei, Zhentong; Lv, Shuang; Wang, Yishu; Sun, Meiyu; Chi, Guangfan; Guo, Jun; Song, Peiye; Fu, Xiaoyu; Zhang, Songling; Li, Yulin


    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 (3.0×10 3 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

  16. Breast cancer stem cells expressing different stem cell markers exhibit distinct biological characteristics. (United States)

    Shao, Jun; Fan, Wei; Ma, Biao; Wu, Yiping


    Identification and isolation of breast cancer stem cells (CSCs) based on CD44/CD24 expression and/or enzymatic activity of aldehyde dehydrogenase 1 (ALDH1). However, the differences among the CD44+/CD24‑/low cells, ALDH1+ cells and the overlap between the sub‑populations have not been frequently investigated. Thus, it is imperative to improve the understanding of breast CSC with different stem markers. CD44+/CD24‑/low, ALDH1+ and ALDH1+CD44+/CD24‑/low cell populations were isolated from fresh breast cancer tissues and analyzed by flow cytometry and immunofluorescence. Mammosphere formation, cell proliferation assay and Transwell experiments, were used to analyze self‑renewal, proliferation and invasion, respectively, for each sub‑population. Finally, in vivo experimentation in mice was performed to evaluate the tumorigenic abilities of the sub‑populations. The sub‑populations of CD44+/CD24‑/low, ALDH1+ and ALDH1+CD44+/CD24‑/low in human breast cancer cells, represented the 7.2, 4.6 and 1.5% of the total tumor cell population, respectively. ALDH1+CD44+/CD24‑/low cells had the strongest ability of self‑renewal, invasion, proliferation and tumorigenicity compared with the other sub‑populations (Pbreast CSCs are heterogeneous, and they exhibit distinct biological characteristics. As ALDH1+CD44+/CD24‑/low cells demonstrated the strongest stem‑like properties, it may be a useful specific stem cell marker. The utilization of more reliable biomarkers to distinguish the breast CSC pool will be important for the development of specific target therapies for breast cancer.

  17. Statins and protein prenylation in cancer cell biology and therapy. (United States)

    Garcia-Ruiz, Carmen; Morales, Albert; Fernandez-Checa, Jose C


    The use of statins has scaled up to become one of the most prescribed medicines in the world and have been very useful in the manegement of cardiovascular diseases and related mortality. The disclosure of their chemical structure similar to that of hydroxy methyl glutaryl-CoA (HMG-CoA) revealed their ability to compete with and inhibit the rate-limiting enzyme HMG-CoA reductase that catalyzes the synthesis of mevalonate, which then serves as the precursor for isoprenoids and cholesterol in the mevalonate pathway. While most of the effects of statins are associated with the lowering of cellular cholesterol levels, it is clear that they also blunt the non-sterol branch of the mevalonate pathway, decreasing formation of isoprenoids and altering protein-prenylation, a critical event in the posttranslational modulation of proteins involved in the regulation of cell cycle progression, proliferation and signaling pathways. Randomized controlled trials for the prevention of cardiovascular diseases indicated that statins elicited provocative and unexpected benefits for reducing a number of different types of cancers, including colorectal carcinoma, melanoma, prostate and hepatocellular carcinoma, although in other cancer types the preclinical expectations of statins were dissapointing. In this review, we will describe the evidence and mechanisms underlying the potential beneficial use of statins and the role of protein prenylation in cancer prevention. Of relevance, the combination of statins with other anti cancer drugs may be a significant asset in malignancies resistant to current therapy.

  18. Unravelling biology and shifting paradigms in cancer with single-cell sequencing. (United States)

    Baslan, Timour; Hicks, James


    The fundamental operative unit of a cancer is the genetically and epigenetically innovative single cell. Whether proliferating or quiescent, in the primary tumour mass or disseminated elsewhere, single cells govern the parameters that dictate all facets of the biology of cancer. Thus, single-cell analyses provide the ultimate level of resolution in our quest for a fundamental understanding of this disease. Historically, this quest has been hampered by technological shortcomings. In this Opinion article, we argue that the rapidly evolving field of single-cell sequencing has unshackled the cancer research community of these shortcomings. From furthering an elemental understanding of intra-tumoural genetic heterogeneity and cancer genome evolution to illuminating the governing principles of disease relapse and metastasis, we posit that single-cell sequencing promises to unravel the biology of all facets of this disease.

  19. Chemotherapy curable malignancies and cancer stem cells: a biological review and hypothesis. (United States)

    Savage, Philip


    Cytotoxic chemotherapy brings routine cures to only a small select group of metastatic malignancies comprising gestational trophoblast tumours, germ cell tumours, acute leukemia, Hodgkin's disease, high grade lymphomas and some of the rare childhood malignancies. We have previously postulated that the extreme sensitivity to chemotherapy for these malignancies is linked to the on-going high levels of apoptotic sensitivity that is naturally linked with the unique genetic events of nuclear fusion, meiosis, VDJ recombination, somatic hypermutation, and gastrulation that have occurred within the cells of origin of these malignancies. In this review we will examine the cancer stem cell/cancer cell relationship of each of the chemotherapy curable malignancies and how this relationship impacts on the resultant biology and pro-apoptotic sensitivity of the varying cancer cell types. In contrast to the common epithelial cancers, in each of the chemotherapy curable malignancies there are no conventional hierarchical cancer stem cells. However cells with cancer stem like qualities can arise stochastically from within the general tumour cell population. These stochastic stem cells acquire a degree of resistance to DNA damaging agents but also retain much of the key characteristics of the cancer cells from which they develop. We would argue that the balance between the acquired resistance of the stochastic cancer stem cell and the inherent chemotherapy sensitivity of parent tumour cell determines the overall chemotherapy curability of each diagnosis. The cancer stem cells in the chemotherapy curable malignancies appear to have two key biological differences from those of the more common chemotherapy incurable malignancies. The first difference is that the conventional hierarchical pattern of cancer stem cells is absent in each of the chemotherapy curable malignancies. The other key difference, we suggest, is that the stochastic stem cells in the chemotherapy curable malignancies

  20. Gene silencing of galectin-3 changes the biological behavior of Eca109 human esophageal cancer cells




    Galectin-3 is a multifunctional ?-galactoside-binding lectin that is involved in multiple biological functions which are upregulated in malignancies, including cell growth, adhesion, proliferation, progression and metastasis, as well as apoptosis. A previous study has confirmed the roles of galecin-3 overexpression in the biological behavior of Eca109 human esophageal cancer (EC) cells. In the present study, small interfering (si)RNA-mediated galectin-3 silencing was performed to analyze the ...

  1. Biological effects of insulin and its analogs on cancer cells with different insulin family receptor expression. (United States)

    Sciacca, Laura; Cassarino, Maria Francesca; Genua, Marco; Vigneri, Paolo; Giovanna Pennisi, Maria; Malandrino, Pasqualino; Squatrito, Sebastiano; Pezzino, Vincenzo; Vigneri, Riccardo


    Hyperinsulinemia is a likely cause of the increased cancer incidence and mortality in diabetic patients, but its role is difficult to define in vivo. Previous in vitro studies testing the mitogenic potential of insulin and its analogs provided incomplete and sometimes contradictory results. To better evaluate cancer cell responsiveness to insulin, to its analogs and to IGF-I, we measured under identical experimental conditions cell proliferation, invasiveness, and foci formation in six cancer cell lines with different insulin receptor family expression levels. The cancer cells studied have a different expression of insulin receptor (IR), its isoforms (IR-A and IR-B), and of the IGF-I receptor. The data indicate that insulin stimulates proliferation in all cancer cell lines, invasiveness in some, and foci formation in none. Cancer cell responses to insulin (and IGF-I) are not related to receptor expression levels; moreover, hormone-stimulated proliferation and invasiveness are not correlated. IGF-I is a more potent stimulator than insulin in most but not all cancer cell lines. Insulin analogs including M1 and M2 Glargine metabolites stimulate cancer cells similar to insulin. However, exceptions occur for specific analogs in particular cancer cells. In conclusion, in vitro insulin is an effective growth factor for all cancer cells but the biological response to insulin cannot be predicted on the basis of receptor expression levels. In the clinical setting, these observations should be taken in account when deciding treatment for diabetic patients who are at risk of undiscovered cancer or survivors of oncological diseases. © 2014 Wiley Periodicals, Inc.

  2. Cell-penetrable lysine dendrimers for anti-cancer drug delivery: synthesis and preliminary biological evaluation. (United States)

    Zhao, Jing; Zhou, Rui; Fu, Xiaoyu; Ren, Wen; Ma, Lifang; Li, Ran; Zhao, Yi; Guo, Li


    Improving the cell penetration and enhancing the cell selectivity of drugs have been approved for overcoming the major drawbacks of chemotherapeutic agents: the toxicity to normal cells and the drug resistance in tumors. In this paper, lysine dendrimers (G1-G3) were chosen as novel cell-penetrating carriers for anti-cancer drugs based on the internalization mechanism of cell-penetrating peptides and the characteristics of dendritic peptides. After labeling with fluorescein isothiocyanate (FITC), the cell-penetrable capacity of lysine dendrimers was certified by flow cytometric analysis. In a preliminary biological evaluation, the conjugates of lysine dendrimers and 5-fluorouracil showed the expected advantages: stable drug release, low toxicity to normal cells, and moderate inhibition of tumor cells. These results imply that cell-penetrable lysine dendrimers could be potential carriers in drug delivery of anti-cancer medicine. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  3. [Biological characteristics of CD55(hig); side population in breast cancer cell line MCF-7]. (United States)

    Yang, Chao; Cui, Zhi-chao; Liu, Yun-jiang; Wang, Shi-jie


    To determine whether the CD55(hig); expression (CD55(hig);) cells in side population (SP) of the cell line MCF-7 possess characteristics of cancer stem cells. Breast cancer cell line MCF-7 was cultured and the nucleic acid dye Hoechst33342 and Verapami were added. Flow cytometry (FCM) was employed to isolate the cells of SP and mian population (MP), the cells were then labeled with CD55 mAb; mean values of fluorescence intensity of CD55 in SP and MP cells were measured. CD55 mAb was used to mark the unsorted MCF-7 cells, the proportion of CD55(hig); cells was determined, and then CD55(hig); cells were sorted and collected, to observe biological characteristics, such as cell morphology, adherence rate, colony formation and cell cycle distribution as well as nude mice implantation. Mean value of fluorescence intensity of CD55 in SP cells was 100.85±4.57, and mean value of fluorescence intensity of CD55 in MP cells was 50.51±4.75; the proportion of CD55(hig); cell in MCF-7 cells was 2.12%; adherent rate of CD55(hig); cells in 24 h was lower than that in CD55(low); cells and 24 h after inoculation adherent rates of both cells had no significant difference (P>0.05); CD55(hig); cells were mostly spherical and kept in a suspended state at 12 hours after inoculation and culture; CD55(hig); cells had the ability of colony formation, the clone-forming rate of CD55(hig); cells was (20.04±1.07)% when the cells were cultured for one week, it was lower than the rate of (27.14±1.07)% in CD55(low); cells (P<0.01); the ratio of G0/G1 resting cells in CD55(hig); cells was (85.4±3.37)% which was higher than that in CD55(low); cells (58.6±2.55)% and in MCF-7 cells (70.73±4.21)%, which had a statistically significant difference (P<0.05). All nude mice implanted with CD55(hig); cells developed the tumor, and the pathological examination of the transplanted tumor had the properties of malignant cells. A few CD55(hig); cells were found in breast cancer MCF-7 cells, and most of CD55

  4. Biological Therapy Following Chemotherapy and Peripheral Stem Cell Transplantation in Treating Patients With Cancer (United States)


    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

  5. Brain Cancer Stem Cells in Adults and Children: Cell Biology and Therapeutic Implications. (United States)

    Abou-Antoun, Tamara J; Hale, James S; Lathia, Justin D; Dombrowski, Stephen M


    Brain tumors represent some of the most malignant cancers in both children and adults. Current treatment options target the majority of tumor cells but do not adequately target self-renewing cancer stem cells (CSCs). CSCs have been reported to resist the most aggressive radiation and chemotherapies, and give rise to recurrent, treatment-resistant secondary malignancies. With advancing technologies, we now have a better understanding of the genetic, epigenetic and molecular signatures and microenvironmental influences which are useful in distinguishing between distinctly different tumor subtypes. As a result, efforts are now underway to identify and target CSCs within various tumor subtypes based on this foundation. This review discusses progress in CSC biology as it relates to targeted therapies which may be uniquely different between pediatric and adult brain tumors. Studies to date suggest that pediatric brain tumors may benefit more from genetic and epigenetic targeted therapies, while combination treatments aimed specifically at multiple molecular pathways may be more effective in treating adult brain tumors which seem to have a greater propensity towards microenvironmental interactions. Ultimately, CSC targeting approaches in combination with current clinical therapies have the potential to be more effective owing to their ability to compromise CSCs maintenance and the mechanisms which underlie their highly aggressive and deadly nature.

  6. Sec62 bridges the gap from 3q amplification to molecular cell biology in non-small cell lung cancer. (United States)

    Linxweiler, Maximilian; Linxweiler, Johannes; Barth, Monika; Benedix, Julia; Jung, Volker; Kim, Yoo-Jin; Bohle, Rainer M; Zimmermann, Richard; Greiner, Markus


    The molecular carcinogenesis of lung cancer has yet to be clearly elucidated. We investigated the possible oncogenic function of SEC62 in lung cancer, which was predicted based on our previous findings that lung and thyroid cancer tissue samples exhibited increased Sec62 protein levels. The SEC62 gene locus is at 3q26.2, and 3q amplification is reportedly the most common genomic alteration in non-small cell lung cancer. We analyzed SEC62 mRNA and protein levels in tissue samples from lung cancer patients by real-time quantitative PCR, Western blot, and IHC and found significantly increased SEC62 mRNA and protein levels in tumors compared with tumor-free tissue samples from the same patients. Correlation analyses revealed significantly higher Sec62 levels in tumors with lymph node metastases compared with nonmetastatic tumors, as well as in poorly compared with moderately differentiated tumors. On the basis of these promising results, we examined the role of Sec62 in cancer cell biology in vitro. Cell migration assays with lung and thyroid cancer cells showed distinct stimulation of migration in SEC62-overexpressing cells and inhibition of migration in Sec62-depleted cells. Moreover, we found that SEC62 silencing sensitized the cells to thapsigargin-induced endoplasmic reticulum stress. Thus, our results indicate that SEC62 represents a potential candidate oncogene in the amplified 3q region in cases of non-small cell lung cancer and harbors various functions in cancer cell biology. Copyright © 2012 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

  7. NK cell-based cancer immunotherapy: from basic biology to clinical application. (United States)

    Li, Yang; Yin, Jie; Li, Ting; Huang, Shan; Yan, Han; Leavenworth, JianMei; Wang, Xi


    Natural killer (NK) cells, which recognize and kill target cells independent of antigen specificity and major histocompatibility complex (MHC) matching, play pivotal roles in immune defence against tumors. However, tumor cells often acquire the ability to escape NK cell-mediated immune surveillance. Thus, understanding mechanisms underlying regulation of NK cell phenotype and function within the tumor environment is instrumental for designing new approaches to improve the current cell-based immunotherapy. In this review, we elaborate the main biological features and molecular mechanisms of NK cells that pertain to regulation of NK cell-mediated anti-tumor activity. We further overview current clinical approaches regarding NK cell-based cancer therapy, including cytokine infusion, adoptive transfer of autologous or allogeneic NK cells, applications of chimeric antigen receptor (CAR)-expressing NK cells and adoptive transfer of memory-like NK cells. With these promising clinical outcomes and fuller understanding the basic questions raised in this review, we foresee that NK cell-based approaches may hold great potential for future cancer immunotherapy.

  8. Cytotoxic Effect on Cancerous Cell Lines by Biologically Synthesized Silver Nanoparticles

    Directory of Open Access Journals (Sweden)

    Balaji Kulandaivelu

    Full Text Available The biosynthesis of nanoparticles has been proposed as an environmental friendly and cost effective alternative to chemical and physical methods. Silver nanoparticles are biologically synthesized and characterized were used in the study. The invitro cytotoxic effect of biologically synthesized silver nanoparticles against MCF-7 cancer cell lines were assessed. The cytotoxic effects of the silver nanoparticles could significantly inhibited MCF-7 cancer cell lines proliferation in a time and concentration-dependent manner by MTT assay. Acridine orange, ethidium bromide (AO/EB dual staining, caspase-3 and DNA fragmentation assays were carried out using various concentrations of silver nanoparticles ranging from 1 to 100 μg/mL. At 100 μg/mL concentration, the silver nanoparticles exhibited significant cytotoxic effects and the apoptotic features were confirmed through caspase-3 activation and DNA fragmentation assays. Western blot analysis has revealed that nanoparticle was able to induce cytochrome c release from the mitochondria, which was initiated by the inhibition of Bcl-2 and activation of Bax. Thus, the results of the present study indicate that biologically synthesized silver nanoparticles might be used to treat breast cancer. The present studies suggest that these nanoparticles could be a new potential adjuvant chemotherapeutic and chemo preventive agent against cytotoxic cells. However, it necessitates clinical studies to ascertain their potential as anticancer agents.

  9. Kat3 coactivators in somatic stem cells and cancer stem cells: biological roles, evolution, and pharmacologic manipulation. (United States)

    Thomas, Paul D; Kahn, Michael


    Long-lived somatic stem cells regenerate adult tissues throughout our lifetime. However, with aging, there is a significant deterioration in the function of stem and progenitor cells, which contribute to diseases of aging. The decision for a long-lived somatic stem cell to become activated and subsequently to undergo either a symmetric or an asymmetric division is a critical cellular decision process. The decision to preferentially divide symmetrically or asymmetrically may be the major fundamental intrinsic difference between normal somatic stem cells and cancer stem cells. Based upon work done primarily in our laboratory over the past 15 years, this article provides a perspective on the critical role of somatic stem cells in aging. In particular, we discuss the importance of symmetric versus asymmetric divisions in somatic stem cells and the role of the differential usage of the highly similar Kat3 coactivators, CREB-binding protein (CBP) and p300, in stem cells. We describe and propose a more complete model for the biological mechanism and roles of these two coactivators, their evolution, and unique roles and importance in stem cell biology. Finally, we discuss the potential to pharmacologically manipulate Kat3 coactivator interactions in endogenous stem cells (both normal and cancer stem cells) to potentially ameliorate the aging process and common diseases of aging.

  10. Biologic characteristics of the side population of human small cell lung cancer cell line H446. (United States)

    Wang, Bo; Yang, Huan; Huang, Yu-Zheng; Yan, Ru-Hong; Liu, Fen-Ju; Zhang, Jun-Ning


    Recently, the theory of cancer stem cells (CSCs) has presented new targets and orientations for tumor therapy. The major difficulties in researching CSCs include their isolation and purification. The aim of this study is to identify and characterize the side population (SP) cells in small cell lung cancer (SCLC) cell line H446, which lays the foundation for the isolation and purification of CSCs. Fluorescence-activated cell sorting (FACS) was used to sort SP and non-SP (NSP) cells from H446. Both subgroups were cultivated to survey the capacity to form into suspended tumor cell spheres. Reverse transcription-polymerase chain reaction (RT-PCR) and real-time PCR were used to evaluate the expression levels of the mRNA of CD133, ABCG2, and nucleostemin in both subgroups. The capacity of proliferation and the differences in drug resistance of both subgroups and unsorted cells were tested by the MTT method. The differentiation ability of both subgroups was determined by FACS. Proliferation was determined by subcutaneous tumor formation in nude mice. The percent of Hoechst 33342 negative cells was about (5.1 +/- 0.2)% in H446 by fluorescence microscopy. The percent of SP cells was (6.3 +/- 0.1)% by flow cytometry. SP cells had a stronger capability of forming into tumor spheres than NSP cells. The mRNA expression levels of ABCG2, CD133, and nucleostemin in SP cells were 21.60 +/- 0.26, 7.10 +/- 0.14, and 1.02 +/- 0.08 folds higher than that in NSP cells (P 0.05, respectively). In vivo, SP cells showed better proliferative ability and tougher viability when treated with drugs. SP cells can differentiate into NSP cells, but NSP cells cannot differentiate into SP cells. SP cells had a greater ability to form tumors. The H446 cell line contained some SP cells with stem cell properties. CD133 and ABCG2 may be cancer stem cell markers of SCLC.

  11. Gene silencing of galectin-3 changes the biological behavior of Eca109 human esophageal cancer cells. (United States)

    Qiao, Lili; Liang, Ning; Xie, Jian; Luo, Hui; Zhang, Jingxin; Deng, Guodong; Li, Yupeng; Zhang, Jiandong


    Galectin-3 is a multifunctional β-galactoside‑binding lectin that is involved in multiple biological functions which are upregulated in malignancies, including cell growth, adhesion, proliferation, progression and metastasis, as well as apoptosis. A previous study has confirmed the roles of galecin-3 overexpression in the biological behavior of Eca109 human esophageal cancer (EC) cells. In the present study, small interfering (si)RNA-mediated galectin-3 silencing was performed to analyze the effects of decreased galectin-3 expression on the biological behavior of EC cells. Western blot and quantitative polymerase chain reaction analyses were utilized to confirm galectin-3 knockdown at the protein and mRNA level (PGalectin-3 knockdown significantly enhanced the apoptotic rate of Eca109 cells compared with that in the siRNA-control and untreated groups (P=0.031 and P=0.047, respectively). In conclusion, following successful knockdown of galecin-3 expression in Eca109 cells, the cell proliferation, migration and invasion were reduced, while the apoptosis was enhanced, which indicates that galectin silencing may represent a therapeutic strategy for EC.

  12. Expression of breast cancer metastasis suppressor-1, BRMS-1, in human breast cancer and the biological impact of BRMS-1 on the migration of breast cancer cells. (United States)

    Zhang, Yulu; Ye, Lin; Tan, Yuxia; Sun, Pinghui; Ji, Ke; Jiang, Wen G


    Breast cancer metastasis suppressor-1 (BRMS1) is a candidate metastasis-suppressing gene and has been shown to potentially inhibit tumor progression without blocking the growth of orthotopic tumors, in different tumor types including non-small cell lung cancer, ovarian, melanoma and breast cancers. BRMS-1 gene transcript was quantified in breast cancer sample tissues and analyzed against histological and clinical patient outcome. Human breast cancer cell lines, MDA MB-231 and MCF-7 were used to genetically-modify the expression of BRMS-1 and test for biological responses following BRMS-1 modifications. Key candidate signal pathways, influenced by BRMS-1 were also explored. BRMS1 was present in MDA MB-231 and MCF-7 cell lines. Using anti-BRMS1 transgenes, we knocked-down the transcripts of BRMS1 in both cells at the mRNA and protein levels. Knockdown of BRMS1 gave both cells a faster cell growth rate, rapid pace of cellular migration and invasion, compared to respective wild-type and control cells (pmetastasis (p=0.05) and those who died of breast cancer (p=0.0037). In addition, patients with low levels of BRMS1 had a significantly shorter overall survival (p=0.035). BRMS-1 is aberrantly expressed in human breast cancer and is inversely-correlated with disease progression and patient survival. This is likely to be occurring via its influence on invasion and migration of breast cancer cells.

  13. Recent advances in non-small cell lung cancer biology and clinical management. (United States)

    Saintigny, Pierre; Burger, Jan A


    Despite advances in surgery, chemotherapy, and radiotherapy over the last decades, the death rate from lung cancer has remained largely unchanged, which is mainly due to metastatic disease. Because of the overall poor prognosis, new treatment strategies for lung cancer patients are urgently needed. In this review, we summarize recent advances in non-small cell lung cancer (NSCLC) screening and diagnostic workup. We discuss current clinical management, highlighting stage-specific therapy approaches, chemotherapy options for advanced-stage patients, along with new agents such as vascular endothelial growth factor (VEGF) and epidermal growth factor receptor (EGFR) monoclonal antibodies, and the EGFR-targeting tyrosine kinase inhibitors erlotinib and gefitinib, and the anaplastic lymphoma kinase (ALK) inhibitor crizotinib. Finally, we give an outlook into NSCLC disease biology, focusing on the importance of EGFR activating mutations and the role of the tumor-microenvironment. CXCR4 chemokine receptors expressed on NSCLC cells are a central pathway of NSCLC cross talk with the tumor microenvironment, as they induce activation, migration, and tumor cell adhesion to stromal cells, which in turn provides growth- and drug resistance-signals. Because of the growing evidence that the microenvironment in NSCLC promotes disease progression, we expect that selected molecular pathways of cross talk between NSCLC cells and their microenvironment will become alternative therapeutic targets in the near future.

  14. Applications of nuclear microprobe analysis in cancer cell biology and pharmacology

    Energy Technology Data Exchange (ETDEWEB)

    Ortega, R. [Bordeaux 1 Univ., 33 Gradignan (France)


    Nuclear microprobe analysis studies in cancer cell pharmacology and biology carried out at Bordeaux-Gradignan are reported. The cellular pharmacology of two anticancer agents, cis-diammine-dichloroplatinum(II), and 4'-iodo-4'-deoxy-doxorubicin, were investigated, as well as the role of iron in neuroblastoma carcinogenesis, and chromium(III) in trans-generation carcinogenesis. Nuclear microprobe analysis, using PIXE and particle backscattering microanalysis, was able to reveal intracellular and tissue distributions of the elements under investigation. Moreover, the fully quantitative and multi-elemental character of nuclear microprobe analysis offered information on possible mechanisms of drug action, metal carcinogenesis, and interactions with endogenous trace elements in cancer cells. (author)

  15. Comparison of tumor biology of two distinct cell sub-populations in lung cancer stem cells. (United States)

    Wang, Jianyu; Sun, Zhiwei; Liu, Yongli; Kong, Liangsheng; Zhou, Shixia; Tang, Junlin; Xing, Hongmei Rosie


    Characterization of the stem-like properties of cancer stem cells (CSCs) remain indirect and qualitative, especially the ability of CSCs to undergo asymmetric cell division for self renewal and differentiation, a unique property of cells of stem origin. It is partly due to the lack of stable cellular models of CSCs. In this study, we developed a new approach for CSC isolation and purification to derive a CSC-enriched cell line (LLC-SE). By conducting five consecutive rounds of single cell cloning using the LLC-SE cell line, we obtained two distinct sub-population of cells within the Lewis lung cancer CSCs that employed largely symmetric division for self-renewal (LLC-SD) or underwent asymmetric division for differentiation (LLC-ASD). LLC-SD and LLC-ASD cell lines could be stably passaged in culture and be distinguished by cell morphology, stem cell marker, spheroid formation and subcutaneous tumor initiation efficiency, as well as orthotopic lung tumor growth, progression and survival. The ability LLC-ASD cells to undergo asymmetric division was visualized and quantified by the asymmetric segregation of labeled BrdU and NUMB to one of the two daughter cells in anaphase cell division. The more stem-like LLC-SD cells exhibited higher capacity for tumorigenesis and progression and shorter survival. As few as 10 LLC-SD could initiate subcutaneous tumor growth when transplanted to the athymic mice. Collectively, these observations suggest that the SD-type of cells appear to be on the top of the hierarchical order of the CSCs. Furthermore, they have lead to generated cellular models of CSC self-renewal for future mechanistic investigations.

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

    Directory of Open Access Journals (Sweden)

    Marcello eMaugeri-Saccà


    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.

  17. Molecular analysis of urothelial cancer cell lines for modeling tumor biology and drug response. (United States)

    Nickerson, M L; Witte, N; Im, K M; Turan, S; Owens, C; Misner, K; Tsang, S X; Cai, Z; Wu, S; Dean, M; Costello, J C; Theodorescu, D


    The utility of tumor-derived cell lines is dependent on their ability to recapitulate underlying genomic aberrations and primary tumor biology. Here, we sequenced the exomes of 25 bladder cancer (BCa) cell lines and compared mutations, copy number alterations (CNAs), gene expression and drug response to BCa patient profiles in The Cancer Genome Atlas (TCGA). We observed a mutation pattern associated with altered CpGs and APOBEC-family cytosine deaminases similar to mutation signatures derived from somatic alterations in muscle-invasive (MI) primary tumors, highlighting a major mechanism(s) contributing to cancer-associated alterations in the BCa cell line exomes. Non-silent sequence alterations were confirmed in 76 cancer-associated genes, including mutations that likely activate oncogenes TERT and PIK3CA, and alter chromatin-associated proteins (MLL3, ARID1A, CHD6 and KDM6A) and established BCa genes (TP53, RB1, CDKN2A and TSC1). We identified alterations in signaling pathways and proteins with related functions, including the PI3K/mTOR pathway, altered in 60% of lines; BRCA DNA repair, 44%; and SYNE1-SYNE2, 60%. Homozygous deletions of chromosome 9p21 are known to target the cell cycle regulators CDKN2A and CDKN2B. This loci was commonly lost in BCa cell lines and we show the deletions extended to the polyamine enzyme methylthioadenosine (MTA) phosphorylase (MTAP) in 36% of lines, transcription factor DMRTA1 (27%) and antiviral interferon epsilon (IFNE, 19%). Overall, the BCa cell line genomic aberrations were concordant with those found in BCa patient tumors. We used gene expression and copy number data to infer pathway activities for cell lines, then used the inferred pathway activities to build a predictive model of cisplatin response. When applied to platinum-treated patients gathered from TCGA, the model predicted treatment-specific response. Together, these data and analysis represent a valuable community resource to model basic tumor biology and to study

  18. Three-dimensional models of cancer for pharmacology and cancer cell biology: capturing tumor complexity in vitro/ex vivo

    NARCIS (Netherlands)

    Hickman, J.A.; Graeser, R.; Hoogt, R. de; Vidic, S.; Brito, C.; Gutekunst, M.; Kuip, H. van der; Schalken, J.A.


    Cancers are complex and heterogeneous pathological "organs" in a dynamic interplay with their host. Models of human cancer in vitro, used in cancer biology and drug discovery, are generally highly reductionist. These cancer models do not incorporate complexity or heterogeneity. This raises the

  19. Nanomedicine to Deal With Cancer Cell Biology in Multi-Drug Resistance. (United States)

    Tekchandani, Pawan; Kurmi, Balak Das; Paliwal, Shivani Rai


    Today Cancer still remains a major cause of mortality and death worldwide, in humans. Chemotherapy, a key treatment strategy in cancer, has significant hurdles such as the occurrence of chemoresistance in cancer, which is inherent unresponsiveness or acquired upon exposure to chemotherapeutics. The resistance of cancer cells to an antineoplastic agent accompanied to other chemotherapeutic drugs with different structures and mechanisms of action called multi-drug resistance (MDR) plays an important role in the failure of chemo- therapeutics. MDR is primarily based on the overexpression of drug efflux pumps in the cellular membrane, which belongs to the ATP-binding cassette (ABC) superfamily of proteins, are P-gp (P-glycoprotein) and multidrug resistance-associated protein (MRP). Over the years, various strategies have been evaluated to overcome MDR, based not only on the use of MDR modulators but also on the implementation an innovative approach and advanced nanosized drug delivery systems. Nanomedicine is an emerging tool of chemotherapy that focuses on alternative drug delivery for improvement of the treatment efficacy and reducing side effects to normal tissues. This review aims to focus on the details biology, reversal strategies option with the limitation of MDR and various advantages of the present medical science nanotechnology with intracellular delivery aspects for overcoming the significant potential for improving the treatment of MDR malignancies. Copyright© Bentham Science Publishers; For any queries, please email at

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

    Directory of Open Access Journals (Sweden)

    Dimitrios Mougiakakos


    Full Text Available 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.

  1. Half-sandwich ruthenium(II) biotin conjugates as biological vectors to cancer cells. (United States)

    Babak, Maria V; Plażuk, Damian; Meier, Samuel M; Arabshahi, Homayon John; Reynisson, Jóhannes; Rychlik, Błażej; Błauż, Andrzej; Szulc, Katarzyna; Hanif, Muhammad; Strobl, Sebastian; Roller, Alexander; Keppler, Bernhard K; Hartinger, Christian G


    Ruthenium(II)-arene complexes with biotin-containing ligands were prepared so that a novel drug delivery system based on tumor-specific vitamin-receptor mediated endocytosis could be developed. The complexes were characterized by spectroscopic methods and their in vitro anticancer activity in cancer cell lines with various levels of major biotin receptor (COLO205, HCT116 and SW620 cells) was tested in comparison with the ligands. In all cases, coordination of ruthenium resulted in significantly enhanced cytotoxicity. The affinity of Ru(II) -biotin complexes to avidin was investigated and was lower than that of unmodified biotin. Hill coefficients in the range 2.012-2.851 suggest strong positive cooperation between the complexes and avidin. To estimate the likelihood of binding to the biotin receptor/transporter, docking studies with avidin and streptavidin were conducted. These explain, to some extent, the in vitro anticancer activity results and support the conclusion that these novel half-sandwich ruthenium(II)-biotin conjugates may act as biological vectors to cancer cells, although no clear relationship between the cellular Ru content, the cytotoxicity, and the presence of the biotin moiety was observed. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  2. Seeing is believing: are cancer stem cells the Loch Ness monster of tumor biology? (United States)

    Lathia, Justin D; Venere, Monica; Rao, Mahendra S; Rich, Jeremy N


    Tumors are complex systems with a diversity of cell phenotypes essential to tumor initiation and maintenance. With the heterogeneity present within the neoplastic compartment as its foundation, the cancer stem cell hypothesis posits that a fraction of tumor cells has the capacity to recapitulate the parental tumor upon transplantation. Over the last decade, the cancer stem cell hypothesis has gained support and shown to be relevant in many highly lethal solid tumors. However, the cancer stem cell hypothesis is not without its controversies and critics question the validity of this hypothesis based upon comparisons to normal somatic stem cells. Cancer stem cells may have direct therapeutic relevance due to resistance to current treatment paradigms, suggesting novel multimodal therapies targeting the cancer stem cells may improve patient outcomes. In this review, we will use the most common primary brain tumor, glioblastoma multiforme, as an example to illustrate why studying cancer stem cells holds great promise for more effective therapies to highly lethal tumors. In addition, we will discuss why the abilities of self-renewal and tumor propagation are the critical defining properties of cancer stem cells. Furthermore, we will examine recent progress in defining appropriate cell surface selection markers and mouse models which explore the potential cell(s) or origin for GBMs. What remains clear is that a population of cells is present in many tumors which are resistant to conventional therapies and must be considered in the design of the next generation of cancer treatments.

  3. Cancer stem cells: a systems biology view of their role in prognosis and therapy. (United States)

    Mertins, Susan D


    Evidence has accumulated that characterizes highly tumorigenic cancer cells residing in heterogeneous populations. The accepted term for such a subpopulation is cancer stem cells (CSCs). While many questions still remain about their precise role in the origin, progression, and drug resistance of tumors, it is clear they exist. In this review, a current understanding of the nature of CSC, their potential usefulness in prognosis, and the need to target them will be discussed. In particular, separate studies now suggest that the CSC is plastic in its phenotype, toggling between tumorigenic and nontumorigenic states depending on both intrinsic and extrinsic conditions. Because of this, a static view of gene and protein levels defined by correlations may not be sufficient to either predict disease progression or aid in the discovery and development of drugs to molecular targets leading to cures. Quantitative dynamic modeling, a bottom up systems biology approach whereby signal transduction pathways are described by differential equations, may offer a novel means to overcome the challenges of oncology today. In conclusion, the complexity of CSCs can be captured in mathematical models that may be useful for selecting molecular targets, defining drug action, and predicting sensitivity or resistance pathways for improved patient outcomes.

  4. Role of EZH2 in cancer stem cells: from biological insight to a therapeutic target (United States)

    Hou, Yaya; Huang, Zaiju; Wang, Zehua


    Epigenetic modifications in cancer stem cells largely result in phenotypic and functional heterogeneity in many solid tumors. Increasing evidence indicates that enhancer of zeste homolog 2 (EZH2), the catalytic subunit of Polycomb repressor complex 2, is highly expressed in cancer stem cells of numerous malignant tumors and has a critical function in cancer stem cell expansion and maintenance. Here, we review up-to-date information regarding EZH2 expression patterns, functions, and molecular mechanisms in cancer stem cells in various malignant tumors and discuss the therapeutic potential of targeting EZH2 in tumors. PMID:28415635

  5. Role of EZH2 in cancer stem cells: from biological insight to a therapeutic target. (United States)

    Wen, Yiping; Cai, Jing; Hou, Yaya; Huang, Zaiju; Wang, Zehua


    Epigenetic modifications in cancer stem cells largely result in phenotypic and functional heterogeneity in many solid tumors. Increasing evidence indicates that enhancer of zeste homolog 2 (EZH2), the catalytic subunit of Polycomb repressor complex 2, is highly expressed in cancer stem cells of numerous malignant tumors and has a critical function in cancer stem cell expansion and maintenance. Here, we review up-to-date information regarding EZH2 expression patterns, functions, and molecular mechanisms in cancer stem cells in various malignant tumors and discuss the therapeutic potential of targeting EZH2 in tumors.

  6. Octamer-binding protein 4 affects the cell biology and phenotypic transition of lung cancer cells involving β-catenin/E-cadherin complex degradation. (United States)

    Chen, Zhong-Shu; Ling, Dong-Jin; Zhang, Yang-De; Feng, Jian-Xiong; Zhang, Xue-Yu; Shi, Tian-Sheng


    Clinical studies have reported evidence for the involvement of octamer‑binding protein 4 (Oct4) in the tumorigenicity and progression of lung cancer; however, the role of Oct4 in lung cancer cell biology in vitro and its mechanism of action remain to be elucidated. Mortality among lung cancer patients is more frequently due to metastasis rather than their primary tumors. Epithelial‑mesenchymal transition (EMT) is a prominent biological event for the induction of epithelial cancer metastasis. The aim of the present study was to investigate whether Oct4 had the capacity to induce lung cancer cell metastasis via the promoting the EMT in vitro. Moreover, the effect of Oct4 on the β‑catenin/E‑cadherin complex, associated with EMT, was examined using immunofluorescence and immunoprecipitation assays as well as western blot analysis. The results demonstrated that Oct4 enhanced cell invasion and adhesion accompanied by the downregulation of epithelial marker cytokeratin, and upregulation of the mesenchymal markers vimentin and N‑cadherin. Furthermore, Oct4 induced EMT of lung cancer cells by promoting β‑catenin/E‑cadherin complex degradation and regulating nuclear localization of β‑catenin. In conclusion, the present study indicated that Oct4 affected the cell biology of lung cancer cells in vitro through promoting lung cancer cell metastasis via EMT; in addition, the results suggested that the association and degradation of the β‑catenin/E‑cadherin complex was regulated by Oct4 during the process of EMT.

  7. Evolutionary foundations for cancer biology. (United States)

    Aktipis, C Athena; Nesse, Randolph M


    New applications of evolutionary biology are transforming our understanding of cancer. The articles in this special issue provide many specific examples, such as microorganisms inducing cancers, the significance of within-tumor heterogeneity, and the possibility that lower dose chemotherapy may sometimes promote longer survival. Underlying these specific advances is a large-scale transformation, as cancer research incorporates evolutionary methods into its toolkit, and asks new evolutionary questions about why we are vulnerable to cancer. Evolution explains why cancer exists at all, how neoplasms grow, why cancer is remarkably rare, and why it occurs despite powerful cancer suppression mechanisms. Cancer exists because of somatic selection; mutations in somatic cells result in some dividing faster than others, in some cases generating neoplasms. Neoplasms grow, or do not, in complex cellular ecosystems. Cancer is relatively rare because of natural selection; our genomes were derived disproportionally from individuals with effective mechanisms for suppressing cancer. Cancer occurs nonetheless for the same six evolutionary reasons that explain why we remain vulnerable to other diseases. These four principles-cancers evolve by somatic selection, neoplasms grow in complex ecosystems, natural selection has shaped powerful cancer defenses, and the limitations of those defenses have evolutionary explanations-provide a foundation for understanding, preventing, and treating cancer.

  8. 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.


    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.

  9. Proteomics-Based Analysis of Protein Complexes in Pluripotent Stem Cells and Cancer Biology. (United States)

    Sudhir, Putty-Reddy; Chen, Chung-Hsuan


    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.

  10. FSH-FSHR3-stem cells in ovary surface epithelium: basis for adult ovarian biology, failure, aging, and cancer. (United States)

    Bhartiya, Deepa; Singh, Jarnail


    Despite extensive research, genetic basis of premature ovarian failure (POF) and ovarian cancer still remains elusive. It is indeed paradoxical that scientists searched for mutations in FSH receptor (FSHR) expressed on granulosa cells, whereas more than 90% of cancers arise in ovary surface epithelium (OSE). Two distinct populations of stem cells including very small embryonic-like stem cells (VSELs) and ovarian stem cells (OSCs) exist in OSE, are responsible for neo-oogenesis and primordial follicle assembly in adult life, and are modulated by FSH via its alternatively spliced receptor variant FSHR3 (growth factor type 1 receptor acting via calcium signaling and the ERK/MAPK pathway). Any defect in FSH-FSHR3-stem cell interaction in OSE may affect folliculogenesis and thus result in POF. Ovarian aging is associated with a compromised microenvironment that does not support stem cell differentiation into oocytes and further folliculogenesis. FSH exerts a mitogenic effect on OSE and elevated FSH levels associated with advanced age may provide a continuous trigger for stem cells to proliferate resulting in cancer, thus supporting gonadotropin theory for ovarian cancer. Present review is an attempt to put adult ovarian biology, POF, aging, and cancer in the perspective of FSH-FSHR3-stem cell network that functions in OSE. This hypothesis is further supported by the recent understanding that: i) cancer is a stem cell disease and OSE is the niche for ovarian cancer stem cells; ii) ovarian OCT4-positive stem cells are regulated by FSH; and iii) OCT4 along with LIN28 and BMP4 are highly expressed in ovarian cancers. © 2015 Society for Reproduction and Fertility.

  11. Regulating Cancer-Associated Fibroblast Biology in Prostate Cancer (United States)


    AWARD NUMBER: W81XWH-15-1-0512 TITLE: Regulating Cancer-Associated Fibroblast Biology in Prostate Cancer PRINCIPAL INVESTIGATOR: Andrew...SUBTITLE 5a. CONTRACT NUMBER Regulating Cancer-Associated Fibroblast Biology in Prostate Cancer 5b. GRANT NUMBER W81XWH-15-1-0512 5c. PROGRAM...blocked by the addition of Pim inhibitors. These results suggest that the Pim protein kinase can regulate stromal cell biology to modulate epithelial


    Directory of Open Access Journals (Sweden)

    N. V. Yunusova


    Full Text Available Objective. To compare the functional activity of natural killer cells in peripheral blood and ascites from patients with different stages of colorectal and ovarian cancers and benign ovarian tumors. Material and methods. The study included 10 patients with stage IIIC ovarian cancer (FIGO, 2009, 5 patients with benign ovarian tumors (BOTs, and 15 patients with colorectal cancer (T2–4N0–2M0 . The control group consisted of 5 healthy donors. To evaluate the number and functional activity of NK-cells in peripheral blood and ascites, the FACS Canto II Flow Cytometer was used. Results. In peripheral blood of patients with ovarian and colorectal cancers, the relative number of activated NK-cells capable of secreting granzyme B (GB (CD56 + CD107a + GB + PF- was significantly lower and the proportion of degranulated NK-cells (CD56 + CD107a + GB- PF- was higher than those of healthy donors. Low total NK-cell counts in peripheral blood were a distinctive feature of ovarian cancer patients (p<0.05. The proportion of activated peripheral blood NK-cells, containing granules of cytolytic enzymes GB and perforin (PF increased with tumor growth. However, lymph node metastasis in patients with colorectal cancer did not affect the level and activation of NK-cells. The comparative analysis of NK-populations in patients with benign and malignant ovarian tumors revealed that the level of CD56 + cells was significantly higher in tumor ascites compared to peripheral blood. In patients with BTs, the levels of CD56 + CD107a + and activated CD56 + CD107a + GB-PF-degranulated cells was higher in ascites than in blood. In patients with ovarian cancer, the level of degranulated cells was higher in peripheral blood than in malignant ascites. Conclusion. The tumor cells and tumor microenvironment were found to affect the number and the functional activity of NK-cells. The accumulation of free fluid within the peritoneal cavity in patients with both benign and malignant

  13. Solar ultraviolet radiation from cancer induction to cancer prevention: solar ultraviolet radiation and cell biology. (United States)

    Tuorkey, Muobarak J


    Although decades have elapsed, researchers still debate the benefits and hazards of solar ultraviolet radiation (UVR) exposure. On the one hand, humans derive most of their serum 25-hydroxycholecalciferol [25(OH)D3], which has potent anticancer activity, from solar UVB radiation. On the other hand, people are more aware of the risk of cancer incidence associated with harmful levels of solar UVR from daily sunlight exposure. Epidemiological data strongly implicate UV radiation exposure as a major cause of melanoma and other cancers, as UVR promotes mutations in oncogenes and tumor-suppressor genes. This review highlights the impact of the different mutagenic effects of solar UVR, along with the cellular and carcinogenic challenges with respect to sun exposure.

  14. Multipotent mesenchymal stromal cells in liver cancer: implications for tumor biology and therapy. (United States)

    Hernanda, Pratika Y; Pedroza-Gonzalez, Alexander; Sprengers, Dave; Peppelenbosch, Maikel P; Pan, Qiuwei


    Remodeling of tumor microenvironment is a hallmark in the pathogenesis of liver cancer. Being a pivotal part of tumor stroma, multipotent mesenchymal stromal cells (MSCs), also known as mesenchymal stem cells (MSCs), are recruited and enriched in liver tumors. Owing to their tumor tropism, MSCs are now emerging as vehicles for anticancer drug/gene delivery against liver cancer. However, the exact impact of MSCs on liver cancer remains elusive, as a variety of effects of these cells that have been reported included a plethora of tumor-promoting effects and anti-oncogenic properties. This review aims to dissect the mechanistic insight regarding this observed discrepancy in different experimental settings of liver cancer. Furthermore, we call for caution using MSCs to treat liver cancer or even premalignant liver diseases, before conclusive evidence for safety and efficacy having been obtained. Copyright © 2014 Elsevier B.V. All rights reserved.

  15. Fabrication and biological evaluation of chitosan coated hyaluronic acid-docetaxel conjugate nanoparticles in CD44(+) cancer cells. (United States)

    Shabani Ravari, Nazanin; Goodarzi, Navid; Alvandifar, Farhad; Amini, Mohsen; Souri, Effat; Khoshayand, Mohammad Reza; Hadavand Mirzaie, Zahra; Atyabi, Fatemeh; Dinarvand, Rassoul


    Hyaluronic acid (HA) has been used for target-specific drug delivery because of strong affinity to CD44, a marker in which overexpressed in cancer cells and cancer stem cells. Conjugation of HA to the cytotoxic agents via active targeting can improve efficacy, biodistribution, and water solubility. To be able to benefit from passive targeting as well, a nanoparticulate system by counter ion using a polycation like chitosan may lead to a perfect delivery system. Water soluble Hyaluronic acid-Docetaxel (HA-DTX) conjugate was prepared and used to formulate chitosan-coated HA-DTX nanoparticles by polyelectrolyte complex (PEC) method and optimized using Box-Behnken design. Biological evaluation of nanoparticles was done in CD44+ cancer cells. Biological evaluation of optimized formula showed IC50 of nanoparticles for 4 T1 and MCF-7 cell lines were 45.34 μM and 354.25 μM against 233.8 μM and 625.9 μM for DTX, respectively with increased cellular uptake showed by inverted confocal microscope. Chitosan-coated HA-DTX nanoparticles were more effective against CD44+ cells than free DTX. Chitosan coated hyaluronic acid-docetaxel conjugate nanoparticles fabricated and evaluated in CD44+ cancer cells.

  16. Ultrasensitive detection of drug resistant cancer cells in biological matrixes using an amperometric nanobiosensor. (United States)

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


    Multidrug resistance (MDR) is a key issue in the failure of cancer chemotherapy and its detection will be helpful to develop suitable therapeutic strategies for cancer patients and overcome the death rates. In this direction, we designed a new amperometric sensor (a medical device prototype) to detect drug resistant cancer cells by sensing "Permeability glycoprotein (P-gp)". The sensor probe is fabricated by immobilizing monoclonal P-gp antibody on the gold nanoparticles (AuNPs) conducting polymer composite. The detection relies on a sandwich-type approach using a bioconjugate, where the aminophenyl boronic acid (APBA) served as a recognition molecule which binds with the cell surface glycans and hydrazine (Hyd) served as an electrocatalyst for the reduction of H2O2 which are attached on multi-wall carbon nanotube (MWCNT) (APBA-MWCNT-Hyd). A linear range for the cancer cell detection is obtained between 50 and 100,000 cells/mL with the detection limit of 23±2 cells/mL. The proposed immunosensor is successfully applied to detect MDR cancer cells (MDRCC) in serum and mixed cell samples. Interferences by drug sensitive (SKBr-3 and HeLa), noncancerous cells (HEK-293 and OSE), and other chemical molecules present in the real sample matrix are examined. The sensitivity of the proposed immunosensor is excellent compared with the conventional reporter antibody based assay. Copyright © 2015 Elsevier B.V. All rights reserved.

  17. Natural Killer Cells in Human Cancer: From Biological Functions to Clinical Applications

    Directory of Open Access Journals (Sweden)

    Estrella Mariel Levy


    Full Text Available Natural killer (NK cells are central components of the innate immunity. In murine models, it has been shown that NK cells can control both local tumor growth and metastasis due to their ability to exert direct cellular cytotoxicity without prior sensitization and to secrete immunostimulatory cytokines like IFN-γ. The latter participates in cancer elimination by inhibiting cellular proliferation and angiogenesis, promoting apoptosis, and stimulating the adaptive immune system, and it is instrumental for enhancing Ag processing and presentation. Nevertheless, NK cells display impaired functionality and capability to infiltrate tumors in cancer patients. Also, NK cells are feasible targets of stimulation to participate in immunotherapeutic approaches like antibody-based strategies and adoptive cell transfer. Thus, multiple attempts currently aim to manipulate NK for utilization in the immunotherapy of cancer.

  18. At the Crossroads of Cancer Stem Cells, Radiation Biology, and Radiation Oncology. (United States)

    Gerweck, Leo E; Wakimoto, Hiroaki


    Reports that a small subset of tumor cells initiate and sustain tumor growth, are resistant to radiation and drugs, and bear specific markers have led to an explosion of cancer stem cell research. These reports imply that the evaluation of therapeutic response by changes in tumor volume is misleading, as volume changes reflect the response of the sensitive rather than the resistant tumorigenic cell population. The reports further suggest that the marker-based selection of the tumor cell population will facilitate the development of radiation treatment schedules, sensitizers, and drugs that specifically target the resistant tumorigenic cells that give rise to treatment failure. This review presents evidence that contests the observations that cancer stem cell markers reliably identify the subset of tumor cells that sustain tumor growth and that the marker-identified population is radioresistant relative to the marker-negative cells. Experimental studies show that cells and tumors that survive large radiation doses are not more radioresistant than unirradiated cells and tumors, and also show that the intrinsic radiosensitivity of unsorted colony-forming tumor cells, in combination with the fraction of unsorted tumor cells that are tumor initiating, predicts tumor radiocurability. ©2016 American Association for Cancer Research.

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

    Directory of Open Access Journals (Sweden)

    Jing Wang


    Full Text Available 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.

  20. Up-regulation of mitochondrial antioxidation signals in ovarian cancer cells with aggressive biologic behavior. (United States)

    Wang, Yue; Dong, Li; Cui, Heng; Shen, Dan-hua; Wang, Ying; Chang, Xiao-hong; Fu, Tian-yun; Ye, Xue; Yao, Yuan-yang


    Recently, a high frequency of mutations in mitochondrial DNA (mtDNA) has been detected in ovarian cancer. To explore the alterations of proteins in mitochondria in ovarian cancer, a pair of human ovarian carcinoma cell lines (SKOV3/SKOV3.ip1) with different metastatic potentials was examined. Cancer cells SKOV3.ip1 were derived from the ascitic tumor cells of nude mice bearing a tumor of ovarian cancer cells SKOV3. SKOV3.ip1 exhibited a higher degree of migration potential than its paired cell line SKOV3. The proteins in the mitochondria of these two cells were isolated and separated by 2-D gel electrophoresis. The differently expressed proteins were extracted and identified using matrix assisted laser desorption ionisation/time-of-flight/time-of-flight (MALDI-TOF/TOF), and finally a selected protein candidate was further investigated by immunohistochemistry (IHC) method in nude mice bearing tumor tissues of these two cells. A total of 35 spots with different expressions were identified between the two cells using 2D-polyacrylamide gel electrophoresis (PAGE) approach. Among them, 17 spots were detected only in either SKOV3 or SKOV3.ip1 cells. Eighteen spots expressed different levels, with as much as a three-fold difference between the two cells. Twenty spots were analyzed using MALDI-TOF/TOF, and 11 of them were identified successfully; four were known to be located in mitochondria, including superoxide dismutase 2 (SOD2), fumarate hydratase (FH), mitochondrial ribosomal protein L38 (MRPL38), and mRNA turnover 4 homolog (MRTO4). An increased staining of SOD2 was observed in SKOV3.ip1 over that of SKOV3 in IHC analysis. Our results indicate that the enhanced antioxidation and metabolic potentials of ovarian cancer cells might contribute to their aggressive and metastatic behaviors. The underlying mechanism warrants further study.

  1. Isoprenoids responsible for protein prenylation modulate the biological effects of statins on pancreatic cancer cells

    Czech Academy of Sciences Publication Activity Database

    Gbelcová, H.; Rimpelová, S.; Knejzlík, Z.; Šáchová, Jana; Kolář, Michal; Strnad, Hynek; Repiska, V.; D'Acunto, C.W.; Ruml, T.; Vítek, L.


    Roč. 16 (2017), č. článku 250. ISSN 1476-511X R&D Projects: GA MZd(CZ) NT13112 Institutional support: RVO:68378050 Keywords : Farmesyl pyrophosphate * Gene expression * Geranylgeranyl pyrophosphate * HMG-CoA reductase inhibitors * Isoprenoids * K-Ras oncogene * Mevalonate * Pncreatic cancer * Prenylation * Statins Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 2.073, year: 2016

  2. The biology of cancer stem cells and its clinical implication in hepatocellular carcinoma. (United States)

    Yoon, Seung Kew


    Hepatocellular carcinoma (HCC) is a highly malignant tumor with limited treatment options in its advanced state. The molecular mechanisms underlying HCC remain unclear because of the complexity of its multi-step development process. Cancer stem cells (CSCs) are defined as a small population of cells within a tumor that possess the capability for self-renewal and the generation of heterogeneous lineages of cancer cells. To date, there have been two theories concerning the mechanism of carcinogenesis, i.e., the stochastic (clonal evolution) model and the hierarchical (cancer stem cell-driven) model. The concept of the CSC has been established over the past decade, and the roles of CSCs in the carcinogenic processes of various cancers, including HCC, have been emphasized. Previous experimental and clinical evidence indicated the existence of liver CSCs; however, the potential mechanistic links between liver CSCs and the development of HCC in humans are not fully understood. Although definitive cell surface markers for liver CSCs have not yet been found, several putative markers have been identified, which allow the prospective isolation of CSCs from HCC. The identification and characterization of CSCs in HCC is essential for a better understanding of tumor initiation or progression in relation to signaling pathways. These markers could be used along with clinical parameters for the prediction of chemoresistance, radioresistance, metastasis and survival and may represent potential targets for the development of new molecular therapies against HCC. This review describes the current evidence for the existence and function of liver CSCs and discuss the clinical implications of CSCs in patients demonstrating resistance to conventional anti-cancer therapies, as well as clinical outcomes. Such data may provide a future perspective for targeted therapy in HCC.

  3. Biological Evaluation of Dipyrromethanes in Cancer Cell Lines: Antiproliferative and Pro-apoptotic Properties

    Czech Academy of Sciences Publication Activity Database

    Jorda, Radek; Lopes, S. M.M.; Řezníčková, Eva; Kryštof, Vladimír; Pinho e Melo, T. M.V.D.


    Roč. 12, č. 9 (2017), s. 701-711 ISSN 1860-7179 R&D Projects: GA MŠk(CZ) LO1204 Institutional support: RVO:61389030 Keywords : anticancer agents * apoptosis * cell cycle * cytotoxicity * dipyrromethanes Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 3.225, year: 2016

  4. [The biological characteristics of beta glucuronidase cDNA transfected renal cancer cell line GRC 1/betaG]. (United States)

    Shao, Chen; Qin, Wei-Jun; Wen, Wei-Hong; Zhang, Lei; Wang, He; Qin, Rong-Liang; Yuan, Jian-Lin; Shao, Guo-Xing


    To establish a renal carcinoma cell line which can highly express beta-glucuronidase(betaG), and to observe the biological characteristics of the transfected cells. Recombinant eukaryotic expression vector pcDNA3.1-betaG was constructed. It was transfected into renal cancer cells GRC-1 via liposome. The transcription and expression of betaG gene were detected by dot blot and Western blot. The biological characteristics of the betaG gene transfected cells was observed under light microscope, transmission electron microscope and flow cytometry. Dot blot and Western blot detection confirmed that the betaG gene had been stably integrated into the genomic DNA of the GRC-1 cells and was highly expressed. Transmission electron microscope observation showed that the lysosomes and endoplasmic reticulum were abundant, the number of microvili and process was significantly increased in the transfected cells, but growth condition and cell cycle of GRC-1 cells had no notable difference before and after transfection. A renal carcinoma cell line that can highly express betaG gene was established, which lays the foundation for further study on gene therapy.

  5. 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


    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

  6. Establishment and Characterization of a Human Small Cell Osteosarcoma Cancer Stem Cell Line: A New Possible In Vitro Model for Discovering Small Cell Osteosarcoma Biology. (United States)

    Palmini, Gaia; Zonefrati, Roberto; Romagnoli, Cecilia; Aldinucci, Alessandra; Mavilia, Carmelo; Leoncini, Gigliola; Franchi, Alessandro; Capanna, Rodolfo; Brandi, Maria Luisa


    Osteosarcoma (OSA) is the most common primary malignant bone tumor, usually arising in the long bones of children and young adults. There are different subtypes of OSA, among which we find the conventional OS (also called medullary or central osteosarcoma) which has a high grade of malignancy and an incidence of 80%. There are different subtypes of high grade OS like chondroblastic, fibroblastic, osteoblastic, telangiectatic, and the small cell osteosarcoma (SCO). In this study, for the first time, we have isolated, established, and characterized a cell line of cancer stem cells (CSCs) from a human SCO. First of all, we have established a primary finite cell line of SCO, from which we have isolated the CSCs by the sphere formation assay. We have proved their in vitro mesenchymal and embryonic stem phenotype. Additionally, we have showed their neoplastic phenotype, since the original tumor bulk is a high grade osteosarcoma. This research demonstrates the existence of CSCs also in human primary SCO and highlights the establishment of this particular stabilized cancer stem cell line. This will represent a first step into the study of the biology of these cells to discover new molecular targets molecules for new incisive therapeutic strategies against this highly aggressive OSA.

  7. Establishment and Characterization of a Human Small Cell Osteosarcoma Cancer Stem Cell Line: A New Possible In Vitro Model for Discovering Small Cell Osteosarcoma Biology

    Directory of Open Access Journals (Sweden)

    Gaia Palmini


    Full Text Available Osteosarcoma (OSA is the most common primary malignant bone tumor, usually arising in the long bones of children and young adults. There are different subtypes of OSA, among which we find the conventional OS (also called medullary or central osteosarcoma which has a high grade of malignancy and an incidence of 80%. There are different subtypes of high grade OS like chondroblastic, fibroblastic, osteoblastic, telangiectatic, and the small cell osteosarcoma (SCO. In this study, for the first time, we have isolated, established, and characterized a cell line of cancer stem cells (CSCs from a human SCO. First of all, we have established a primary finite cell line of SCO, from which we have isolated the CSCs by the sphere formation assay. We have proved their in vitro mesenchymal and embryonic stem phenotype. Additionally, we have showed their neoplastic phenotype, since the original tumor bulk is a high grade osteosarcoma. This research demonstrates the existence of CSCs also in human primary SCO and highlights the establishment of this particular stabilized cancer stem cell line. This will represent a first step into the study of the biology of these cells to discover new molecular targets molecules for new incisive therapeutic strategies against this highly aggressive OSA.

  8. HEK293 in cell biology and cancer research: phenotype, karyotype, tumorigenicity, and stress-induced genome-phenotype evolution. (United States)

    Stepanenko, A A; Dmitrenko, V V


    293 cell line (widely known as the Human Embryonic Kidney 293 cells) and its derivatives were the most used cells after HeLa in cell biology studies and after CHO in biotechnology as a vehicle for the production of adenoviral vaccines and recombinant proteins, for analysis of the neuronal synapse formation, in electrophysiology and neuropharmacology. Despite the historically long-term productive exploitation, the origin, phenotype, karyotype, and tumorigenicity of 293 cells are still debated. 293 cells were considered the kidney epithelial cells or even fibroblasts. However, 293 cells demonstrate no evident tissue-specific gene expression signature and express the markers of renal progenitor cells, neuronal cells and adrenal gland. This complicates efforts to reveal the authentic cell type/tissue of origin. On the other hand, the potential to propagate the highly neurotropic viruses, inducible synaptogenesis, functionality of the endogenous neuron-specific voltage-gated channels, and response to the diverse agonists implicated in neuronal signaling give credibility to consider 293 cells of neuronal lineage phenotype. The compound phenotype of 293 cells can be due to heterogeneous, unstable karyotype. The mean chromosome number and chromosome aberrations differ between 293 cells and derivatives as well as between 293 cells from the different cell banks/labs. 293 cells are tumorigenic, whereas acute changes of expression of the cancer-associated genes aggravate tumorigenicity by promoting chromosome instability. Importantly, the procedure of a stable empty vector transfection can also impact karyotype and phenotype. The discussed issues caution against misinterpretations and pitfalls during the different experimental manipulations with 293 cells. Copyright © 2015 Elsevier B.V. All rights reserved.

  9. Separating biological cells (United States)

    Brooks, D. E.


    Technique utilizing electric field to promote biological cell separation from suspending medium in zero gravity increases speed, reduces sedimentation, and improves efficiency of separation in normal gravity.

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

    Energy Technology Data Exchange (ETDEWEB)

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


    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. Targeted therapies for the treatment of non-small-cell lung cancer: Monoclonal antibodies and biological inhibitors. (United States)

    Silva, Ana P S; Coelho, Priscila V; Anazetti, Maristella; Simioni, Patricia U


    The usual treatments for patients with non-small-cell lung cancer (NSCLC), such as advanced lung adenocarcinoma, are unspecific and aggressive, and include lung resection, radiotherapy and chemotherapy. Recently, treatment with monoclonal antibodies and biological inhibitors has emerged as an effective alternative, generating effective results with few side effects. In recent years, several clinical trials using monoclonal antibodies presented potential benefits to NSCLC, and 4 of them are already approved for the treatment of NSCLC, such as cetuximab, bevacizumab, nivolumab and pembrolizumab. Also, biological inhibitors are attractive tolls for biological applications. Among the approved inhibitors are crizotinib, erlotinib, afatinib and gefitinib, and side effects are usually mild to intense. Nevertheless, biological molecule treatments are under development, and several new monoclonal antibodies and biological inhibitors are in trial to treat NSCLC. Also under trial study are as follows: anti-epidermal growth factor receptor (EGFR) antibodies (nimotuzumab and ficlatuzumab), anti-IGF 1 receptor (IGF-1R) monoclonal antibody (figitumumab), anti-NR-LU-10 monoclonal antibody (nofetumomab) as well as antibodies directly affecting the cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) molecule (ipilimumab and tremelimumab), to receptor activator of nuclear factor-kappa B ligand (RANKL) (denosumab) or to polymerase enzyme (veliparib and olaparib). Among new inhibitors under investigation are poly-ADP ribose polymerase (PARP) inhibitors (veliparib and olaparib) and phosphatidylinositol 3-kinase (PI3K) inhibitor (buparlisib). However, the success of immunotherapies still requires extensive research and additional controlled trials to evaluate the long-term benefits and side effects.

  12. [Biology of cancer metastasis]. (United States)

    Robert, Jacques


    Metastatic dissemination represents the true cause of the malignant character of cancers. Its targeting is much more difficult than that of cell proliferation, because metastasis, like angiogenesis, involves a number of complex interactions between tumour and stroma; the contribution of adhesion and motility pathways is added to that of proliferation and survival pathways. Long distance extension, discontinuous in respect to the primitive tumour, is a major feature of cancer and the main cause of patients' death. Cancer cells use two main dissemination pathways: the lymphatic pathway, leading to the invasion of the lymph nodes draining the organs where the tumour evolves; and the blood pathway, leading to the invasion of distant organs such as liver, brain, bone or lung. Metastasis is inscribed within the properties of the primitive tumour, as shown by the comparative molecular analysis of the primitive tumour and its own metastases: their similarity is always more important than what could be expected from the general activation of "metastasis genes" or the inhibition of "metastasis suppressor genes". Among the signalling pathways involved in metastasis, one can mention the integrin pathway, the transforming growth factor beta (TGFβ) pathway, the chemokine pathway, the dependence receptor pathway and many others. These pathways allow the possibility of therapeutic targeting, thanks to therapeutic antibodies or small molecules inhibiting the kinases involved in these signalling pathways, but not a single properly anti-metastatic drug has yet been proposed: the complexity and the diversity of the processes allowing metastasis emergence, as well as the fact that the activation mechanisms are more often epigenetic than genetic and are generally physiological processes misled by the malignant cell, render especially difficult the therapeutic approach of metastasis.

  13. [Effects of RNAi-silenced id1 gene on the biology behavior of esophageal cancer cell lines Eca-109]. (United States)

    Pei, Fei; Zhang, Tang-Tong; Zhang, Na-Juan; Yang, Chao; Yang, Chun-Lei


    To study the effect of shRNA expressing vector targeting to id1 gene on the biological behavior of the esophageal cancer cell. The specific shRNA sequence was designed, synthesized and cloned into pGFU6/neo vector. Then, the resulting recombinants were transfected into Eca-109 cells using Lipofetamine 2000 following the instruction of the manufactures. The expression levels of id1 mRNA were analyzed by RT-PCR and the levels of Id1, p16 and PCNA protein were detected by Western blot assay. The growth of Eca-109 cells was analyzed using clone formation assay and trypan blue exclusion assay. Distribution of cell cycle and proliferation of Eca-109 cells were assessed by flow cytometry. The sequence of recombinant plasmid was confirmed by sequence analysis. The expression levels of id1 mRNA and Id1 protein significantly decreased in Eca-109 cells transfected with pGFU6/neo-Id1-1 vector compared to the negative control group (P Eca-109 cells transfected with pGFU6/neo-id1-1 recombinant. Furthermore, the proliferation of id1 knockdown cells was depressed.

  14. Synthesis and Biological Activity of 6-Selenocaffeine: Potential Modulator of Chemotherapeutic Drugs in Breast Cancer Cells

    Directory of Open Access Journals (Sweden)

    Inês L. Martins


    Full Text Available We report the development of a new microwave-based synthetic methodology mediated by Woollins’ reagent that allowed an efficient conversion of caffeine into 6-selenocaffeine. A preliminary evaluation on the modulation of antioxidant activity upon selenation of caffeine, using the DPPH assay, indicated a mild antioxidant activity for 6-selenocaffeine, contrasting with caffeine, that exhibited no antioxidant activity under the same experimental conditions. Interestingly, whereas 6-selenocaffeine has revealed to have a low cytotoxic potential in both MCF10A and MCF-7 breast cells (24 h, up to 100 µM, MTT assay, a differential effect was observed when used in combination with the anticancer agents doxorubicin and oxaliplatin in MCF-7 breast cancer cells. The co-treatment of doxorubicin (1 µM and 6-selenocaffeine (100 µM resulted in a slight decrease in cellular viability when compared to doxorubicin (1 µM alone. Conversely, the seleno-caffeine derivative at the same concentration markedly increased the viability of oxaliplatin (100 µM-treated cells (p < 0.01. Overall, this work highlights an emerging methodology to synthesize organoselenium compounds and points out the differential roles of 6-selenocaffeine in the modulation of the cytotoxicity of anticancer agents.

  15. 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: [Laboratory of Cellular and Molecular Radiation Oncology, Massachusetts General Hospital, Boston, Massachusetts (United States)


    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.

  16. Skin Cancer: Biology, Risk Factors & Treatment (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 ...

  17. Expression of transcription factor Oct4 in bladder cancer cell line T24 and its effects on the biological characteristics of the cells. (United States)

    Zhu, Zhiqiang; Wen, Jianguo; Zheng, Xiangyu; Wang, Daoxie; Wang, Qingwei; Fan, Changhui


    The expression of octamer binding factor 4 (Oct4) gene in bladder cancer cell line T24 and its effects on the biological characteristics of the cells were investigated. RT-PCR and Western blot were employed to detect the expression of Oct4 in T24 cells. The changes of biological characteristics in T24 cells were analyzed before and after gene-silencing by Boyden chamber and MTT. The results showed that the expression of Oct4 gene was detectable in T24 cells by RT-PCR and Western blot. The expression of Oct4 gene and protein was down-regulated by siRNA, and average number of transwell cells in interference group, negative control group and blank control group was 101.40+/-4.56, 104.20+/-10.03 and 111.00+/-11.90, respectively. There was significant difference in the proliferation ability of the cells from 48 h, 72 h to 96 h after the interference by siRNA between interference group and negative group or blank control group (PT24 cells, but not with invasive capability.

  18. Omics/systems biology and cancer cachexia. (United States)

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


    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. Copyright © 2016. Published by Elsevier Ltd.

  19. A systems biology approach for miRNA-mRNA expression patterns analysis in non-small cell lung cancer. (United States)

    Najafi, Ali; Tavallaei, Mahmood; Hosseini, Sayed Mostafa


    Non-small cell lung cancers (NSCLCs) is a prevalent and heterogeneous subtype of lung cancer accounting for 85 percent of patients. MicroRNAs (miRNAs), a class of small endogenous non-coding RNAs, incorporate into regulation of gene expression post-transcriptionally. Therefore, deregulation of miRNAs' expression has provided further layers of complexity to the molecular etiology and pathogenesis of different diseases and malignancies. Although, until now considerable number of studies has been carried out to illuminate this complexity in NSCLC, they have remained less effective in their goal due to lack of a holistic and integrative systems biology approach which considers all natural elaborations of miRNAs' function. It is able to reliably nominate most affected signaling pathways and therapeutic target genes by deregulated miRNAs during a particular pathological condition. Herein, we utilized a holistic systems biology approach, based on appropriate re-analyses of microarray datasets followed by reliable data filtering, to analyze integrative and combinatorial deregulated miRNA-mRNA interaction network in NSCLC, aiming to ascertain miRNA-dysregulated signaling pathway and potential therapeutic miRNAs and mRNAs which represent a lion' share during various aspects of NSCLC's pathogenesis. Our systems biology approach introduced and nominated 1) important deregulated miRNAs in NSCLCs compared with normal tissue 2) significant and confident deregulated mRNAs which were anti-correlatively targeted by deregulated miRNA in NSCLCs and 3) dysregulated signaling pathways in association with deregulated miRNA-mRNAs interactions in NSCLCs. These results introduce possible mechanism of function of deregulated miRNAs and mRNAs in NSCLC that could be used as potential therapeutic targets.

  20. Systems biology analysis of drivers underlying hallmarks of cancer cell metabolism (United States)

    Zielinski, Daniel C.; Jamshidi, Neema; Corbett, Austin J.; Bordbar, Aarash; Thomas, Alex; Palsson, Bernhard O.


    Malignant transformation is often accompanied by significant metabolic changes. To identify drivers underlying these changes, we calculated metabolic flux states for the NCI60 cell line collection and correlated the variance between metabolic states of these lines with their other properties. The analysis revealed a remarkably consistent structure underlying high flux metabolism. The three primary uptake pathways, glucose, glutamine and serine, are each characterized by three features: (1) metabolite uptake sufficient for the stoichiometric requirement to sustain observed growth, (2) overflow metabolism, which scales with excess nutrient uptake over the basal growth requirement, and (3) redox production, which also scales with nutrient uptake but greatly exceeds the requirement for growth. We discovered that resistance to chemotherapeutic drugs in these lines broadly correlates with the amount of glucose uptake. These results support an interpretation of the Warburg effect and glutamine addiction as features of a growth state that provides resistance to metabolic stress through excess redox and energy production. Furthermore, overflow metabolism observed may indicate that mitochondrial catabolic capacity is a key constraint setting an upper limit on the rate of cofactor production possible. These results provide a greater context within which the metabolic alterations in cancer can be understood.

  1. Translational environmental biology: cell biology informing conservation. (United States)

    Traylor-Knowles, Nikki; Palumbi, Stephen R


    Typically, findings from cell biology have been beneficial for preventing human disease. However, translational applications from cell biology can also be applied to conservation efforts, such as protecting coral reefs. Recent efforts to understand the cell biological mechanisms maintaining coral health such as innate immunity and acclimatization have prompted new developments in conservation. Similar to biomedicine, we urge that future efforts should focus on better frameworks for biomarker development to protect coral reefs. Copyright © 2014 Elsevier Ltd. All rights reserved.

  2. Spherical Cancer Models in Tumor Biology

    Directory of Open Access Journals (Sweden)

    Louis-Bastien Weiswald


    Full Text Available Three-dimensional (3D in vitro models have been used in cancer research as an intermediate model between in vitro cancer cell line cultures and in vivo tumor. Spherical cancer models represent major 3D in vitro models that have been described over the past 4 decades. These models have gained popularity in cancer stem cell research using tumorospheres. Thus, it is crucial to define and clarify the different spherical cancer models thus far described. Here, we focus on in vitro multicellular spheres used in cancer research. All these spherelike structures are characterized by their well-rounded shape, the presence of cancer cells, and their capacity to be maintained as free-floating cultures. We propose a rational classification of the four most commonly used spherical cancer models in cancer research based on culture methods for obtaining them and on subsequent differences in sphere biology: the multicellular tumor spheroid model, first described in the early 70s and obtained by culture of cancer cell lines under nonadherent conditions; tumorospheres, a model of cancer stem cell expansion established in a serum-free medium supplemented with growth factors; tissue-derived tumor spheres and organotypic multicellular spheroids, obtained by tumor tissue mechanical dissociation and cutting. In addition, we describe their applications to and interest in cancer research; in particular, we describe their contribution to chemoresistance, radioresistance, tumorigenicity, and invasion and migration studies. Although these models share a common 3D conformation, each displays its own intrinsic properties. Therefore, the most relevant spherical cancer model must be carefully selected, as a function of the study aim and cancer type.

  3. Molecular and biological interactions in colorectal cancer

    NARCIS (Netherlands)

    Heer, Pieter de


    The current thesis discusses the use of molecular and biological tumor markers to predict clinical outcome. By studying several key processes in the develepment of cancer as regulation of cell motility (non-receptor protein tyrosin adesion kinases, FAK, Src and paxillin, Apoptosis (caspase-3

  4. Methods in Molecular Biology: Germline Stem Cells | Center for Cancer Research (United States)

    The protocols in Germline Stem Cells are intended to present selected genetic, molecular, and cellular techniques used in germline stem cell research. The book is divided into two parts. Part I covers germline stem cell identification and regulation in model organisms. Part II covers current techniques used in in vitro culture and applications of germline stem cells.

  5. Biology of Schwann cells. (United States)

    Kidd, Grahame J; Ohno, Nobuhiko; Trapp, Bruce D


    The fundamental roles of Schwann cells during peripheral nerve formation and regeneration have been recognized for more than 100 years, but the cellular and molecular mechanisms that integrate Schwann cell and axonal functions continue to be elucidated. Derived from the embryonic neural crest, Schwann cells differentiate into myelinating cells or bundle multiple unmyelinated axons into Remak fibers. Axons dictate which differentiation path Schwann cells follow, and recent studies have established that axonal neuregulin1 signaling via ErbB2/B3 receptors on Schwann cells is essential for Schwann cell myelination. Extracellular matrix production and interactions mediated by specific integrin and dystroglycan complexes are also critical requisites for Schwann cell-axon interactions. Myelination entails expansion and specialization of the Schwann cell plasma membrane over millimeter distances. Many of the myelin-specific proteins have been identified, and transgenic manipulation of myelin genes have provided novel insights into myelin protein function, including maintenance of axonal integrity and survival. Cellular events that facilitate myelination, including microtubule-based protein and mRNA targeting, and actin based locomotion, have also begun to be understood. Arguably, the most remarkable facet of Schwann cell biology, however, is their vigorous response to axonal damage. Degradation of myelin, dedifferentiation, division, production of axonotrophic factors, and remyelination all underpin the substantial regenerative capacity of the Schwann cells and peripheral nerves. Many of these properties are not shared by CNS fibers, which are myelinated by oligodendrocytes. Dissecting the molecular mechanisms responsible for the complex biology of Schwann cells continues to have practical benefits in identifying novel therapeutic targets not only for Schwann cell-specific diseases but other disorders in which axons degenerate. Copyright © 2013 Elsevier B.V. All rights

  6. Biological Therapies for Cancer (United States)

    ... promotes the development of tumor blood vessels . When bound to bevacizumab, VEGF cannot interact with its cellular ... grow large numbers of these modified cells in culture. The genetically modified cells are then infused into ...

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

  8. Cell Biology and Cancer. Grades 9-12. NIH Curriculum Supplement Series. (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…

  9. Biological characteristics of Taxol‑resistant ovarian cancer cells and reversal of Taxol resistance by adenovirus expressing p53. (United States)

    Liu, Qun; Sui, Rui; Li, Ruirui; Miao, Jinwei; Liu, Jian


    The development of acquired drug resistance is the primary cause of chemotherapy failure in the treatment of ovarian cancer. To examine the mechanism underlying Taxol (TAX) resistance in ovarian cancer and attempt to reverse it, the present study induced a TAX‑resistant ovarian cancer cell line SKOV3/TAX using a gradient concentration increment method. The properties of the resistant cell line were initially investigated by proliferation, colony formation, adhesion and cell cycle analysis compared with control SKOV3 cells. To examine the mechanism, the expression of p53 upregulated modulator of apoptosis (PUMA) was compared between SKOV3/TAX and SKOV3 cells by western blot analysis. An adenovirus expressing p53 (Ad‑p53), alone or in combination with TAX, was used to treat the drug‑resistant ovarian cancer cells SKOV3/TAX. The effects of Ad‑p53 on pro‑apoptosis and the reversal of drug resistance were evaluated using flow cytometric analysis, cleaved‑poly ADP‑ribose polymerase detection, microscopic observation and MTT measurement. Compared with the control cells, the TAX‑resistant ovarian cancer cell line SKOV3/TAX was characterized by reduced sensitivity to TAX treatment, a significantly slower proliferation rate, higher colony‑forming efficiency and higher adhesion ability. However, no significant difference in cell cycle distribution was identified. PUMA, a potent pro‑apoptotic protein, was markedly suppressed in the SKOV3/TAX cells. Ad‑p53 infection stimulated the upregulation of PUMA and re‑sensitized the resistant ovarian cancer cells to TAX by an apoptotic mechanism. Therefore, Ad‑p53 infection is an effective gene therapy method to re‑sensitize the resistant ovarian cancer cells to TAX by restoring the expression of PUMA.

  10. 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

    Energy Technology Data Exchange (ETDEWEB)

    Narang, Himanshi, E-mail: [Radiation Biology and Health Sciences Division, Bhabha Atomic Research Centre, Mumbai 400085 (India); Kumar, Amit [Radiation Biology and Health Sciences Division, Bhabha Atomic Research Centre, Mumbai 400085 (India); Bhat, Nagesh [Radiological Physics and Advisory Division, Bhabha Atomic Research Centre, Mumbai 400085 (India); Pandey, Badri N.; Ghosh, Anu [Radiation Biology and Health Sciences Division, Bhabha Atomic Research Centre, Mumbai 400085 (India)


    Highlights: • Biological effectiveness of proton and gamma irradiation is compared in A549 cells. • Proton irradiation is two times more cytotoxic than gamma irradiation. • It alters ten times more number of early genes, as observed by microarray study. • It does not enhance cell migration, invasion and adhesion, unlike gamma irradiation. • It was more effective in reducing the percentage of cancer stem cell like cells. - Abstract: 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 (3 MeV) 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{sup +}, 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.

  11. 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:


    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.

  12. [Cell biology and cosmetology]. (United States)

    Traniello, S; Cavalletti, T


    Cellular biology can become the natural support of research in the field of cosmetics because it is able to provide alternative experimental models which can partially replace the massive use of laboratory animals. Cultures of human skin cells could be used in tests investigating irritation of the skin. We have developed an "in vitro" experimental model that allows to evaluate the damage caused by the free radicals to the fibroblasts in culture and to test the protective action of the lipoaminoacids. Experimenting on human cell cultures presents the advantage of eliminating the extrapolation between the different species, of allowing a determination of the biological action of a substance and of evaluating its dose/response effect. This does not mean that "in vitro" experimenting could completely replace experimenting on living animals, but the "in vitro" model can be introduced in the realisation of preliminary screenings.

  13. The biological sense of cancer: a hypothesis

    Directory of Open Access Journals (Sweden)

    Bustuoabad Oscar D


    Full Text Available Abstract Background Most theories about cancer proposed during the last century share a common denominator: cancer is believed to be a biological nonsense for the organism in which it originates, since cancer cells are believed to be ones evading the rules that control normal cell proliferation and differentiation. In this essay, we have challenged this interpretation on the basis that, throughout the animal kingdom, cancer seems to arise only in injured organs and tissues that display lost or diminished regenerative ability. Hypothesis According to our hypothesis, a tumor cell would be the only one able to respond to the demand to proliferate in the organ of origin. It would be surrounded by "normal" aged cells that cannot respond to that signal. According to this interpretation, cancer would have a profound biological sense: it would be the ultimate way to attempt to restore organ functions and structures that have been lost or altered by aging or noxious environmental agents. In this way, the features commonly associated with tumor cells could be reinterpreted as progressively acquired adaptations for responding to a permanent regenerative signal in the context of tissue injury. Analogously, several embryo developmental stages could be dependent on cellular damage and death, which together disrupt the field topography. However, unlike normal structures, cancer would have no physiological value, because the usually poor or non-functional nature of its cells would make their reparative task unattainable. Conclusion The hypothesis advanced in this essay might have significant practical implications. All conventional therapies against cancer attempt to kill all cancer cells. However, according to our hypothesis, the problem might not be solved even if all the tumor cells were eradicated. In effect, if the organ failure remained, new tumor cells would emerge and the tumor would reinitiate its progressive growth in response to the permanent

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

    DEFF Research Database (Denmark)

    Møller, Michael Boe


    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...... D3 is important in lymphomagenesis. However, further studies are needed to implicate cyclin D3 definitively as an oncoprotein. Our data contain several lines of evidence supporting roles of CDKN2A and MDM2 in progression of neoplastic disease. We found that loss of p16INK4A coincided...

  15. Mesangial cell biology

    Energy Technology Data Exchange (ETDEWEB)

    Abboud, Hanna E., E-mail:


    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.

  16. Screening of multi-targeted natural compounds for receptor tyrosine kinases inhibitors and biological evaluation on cancer cell lines, in silico and in vitro. (United States)

    Singh, Pushpendra; Bast, Felix


    Receptors for growth factors encompass within the superfamily of receptor tyrosine kinases and are known to regulate numerous biological processes including cellular growth, proliferation, metabolism, survival, cell differentiation and apoptosis. These receptors have recently caught the attention of the researchers as an attractive target to combat cancer owing to the evidence suggesting their over-expression in cancer cells. Therefore, we studied receptor-based molecular docking of IR (PDB; 3ETA), IGF1R (PDB; 1K3A), EGFR (PDB; 1M17), VEGFIR (PDB; 3HNG), and VEGFIIR (PDB; 2OH4) against natural compounds. Further, in vitro investigation of the biological effect of lead molecules in an array of cancer cell lines was done. All selected natural compounds were docked with the X-ray crystal structure of selected protein by employing GLIDE (Grid-based Ligand Docking with Energetics) Maestro 9.6. InterBioScreen natural compounds docked with each selected protein molecules by using GLIDE high throughput virtual screening. On the basis of Gscore, we select 20 compounds along with 68 anticancer compounds for GLIDE extra precision molecular docking. It was discovered in this study that compound epigallocatechin gallate (EGCG) yielded magnificent Gscore with IGF1R (PDB; 1K3A) and VEGFIIR (PDB; 2OH4), and protein-ligand interactions are chart out. Effect of EGCG on biological activity such as mRNA expression of selected protein, cell proliferation, oxidative stress, and cell migration was reported after the 48 h treatments in cancer cell lines. The RT-PCR densitometric bands analysis showed that compound EGCG reduced the mRNA expression of IGF1R, VEGFIIR, and mTOR at 80 μM concentration. Moreover, EGCG significantly reduced cell proliferation and ROS generation after 48 h treatments. Our result also indicated a reduction in the potential for cell migration that might show in vivo anti-metastasis activity of EGCG.

  17. 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.

  18. 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


    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

  19. Comprehensive data-driven analysis of the impact of chemoinformatic structure on the genome-wide biological response profiles of cancer cells to 1159 drugs. (United States)

    Khan, Suleiman A; Faisal, Ali; Mpindi, John Patrick; Parkkinen, Juuso A; Kalliokoski, Tuomo; Poso, Antti; Kallioniemi, Olli P; Wennerberg, Krister; Kaski, Samuel


    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. 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. 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 to build better models of drug effects, including

  20. [Molecular biology in gastric cancer]. (United States)

    Kikuchi, K; Ueda, M; Kitajima, M


    In gastric cancer, the process of carcinogenesis is thought to occur as a stepwise accumulation of genetic abnormalities. However, the mechanisms of the process of multistage carcinogenesis is still unknown for gastric cancer. Gene abnormalities seen in gastric cancer, including ras, myc, c-erbB-2, met, K-sam and cript are summarized herein. Abnormalities of cancer suppressor genes, including p53, RB and APC are also described. In our studies, the biological malignancy of patients with c-erbB-2 amplification was higher than that of patients without amplification. Moreover, the cases with amplification of c-erbB-2 were found to be highly correlated with distant organ metastasis. However, very little is currently known of the molecular abnormalities leading to gastric cancer. In order to clarify the multiple gene abnormalities in gastric cancer, we used the method of restriction landmark genomic scanning (RLGS). RLGS provides a useful method for genomic analysis of gastric cancer. In the future, new analytical methods that will permit screening of all gene abnormalities at once promise to improve our understanding of the mechanisms of gastric cancer.

  1. Synthetic biology approaches to engineer T cells. (United States)

    Wu, Chia-Yung; Rupp, Levi J; Roybal, Kole T; Lim, Wendell A


    There is rapidly growing interest in learning how to engineer immune cells, such as T lymphocytes, because of the potential of these engineered cells to be used for therapeutic applications such as the recognition and killing of cancer cells. At the same time, our knowhow and capability to logically engineer cellular behavior is growing rapidly with the development of synthetic biology. Here we describe how synthetic biology approaches are being used to rationally alter the behavior of T cells to optimize them for therapeutic functions. We also describe future developments that will be important in order to construct safe and precise T cell therapeutics. Copyright © 2015 Elsevier Ltd. All rights reserved.

  2. Stem cells and solid cancers. (United States)

    McDonald, Stuart A C; Graham, Trevor A; Schier, Stefanie; Wright, Nicholas A; Alison, Malcolm R


    Recently, there have been significant advances in our knowledge of stem cells found in tissues that can develop solid tumours. In particular, novel stem cell markers have been identified for the first time identifying multipotential cells: a required characteristic of a stem cell. The scarcity of cancer stem cells has been questioned. Current dogma states that they are rare, but novel research has suggested that this may not be the case. Here, we review the latest literature on stem cells, particularly cancer stem cells within solid tumours. We discuss current thinking on how stem cells develop into cancer stem cells and how they protect themselves from doing so and do they express unique markers that can be used to detect stem cells. We attempt to put into perspective these latest advances in stem cell biology and their potential for cancer therapy.

  3. 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 (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


    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

  4. Illuminating Cell Biology (United States)


    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.

  5. Comparative Phytochemical Analysis of Essential Oils from Different Biological Parts of Artemisia herba alba and Their Cytotoxic Effect on Cancer Cells (United States)

    Tilaoui, Mounir; Ait Mouse, Hassan; Jaafari, Abdeslam; Zyad, Abdelmajid


    Purpose Carrying out the chemical composition and antiproliferative effects against cancer cells from different biological parts of Artemisia herba alba. Methods 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. Results 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. Conclusion 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. PMID:26196123

  6. [Molecular biology of ovarian cancer]. (United States)

    Tanaka, K


    It has been suggested that the accumulation in multiple steps of gene abnormality is related to the malignant transformation of the normal cell. Understanding such abnormalities would be useful in the establishment of effective measures for the early detection and treatment of cancers with poor prognoses. In gynecological malignancies, the prognosis for epithelial ovarian cancer is poor even though great numbers of patients are treated with multimodal therapy. Uncovering the genes associated with the epithelial ovarian cancer crisis could lead to the identification of high risk cases, and accurate screening could open the way to early detection. Among the genes searched to date for abnormalities related to ovarian cancer, BRCA1 is thought to be the most likely candidate for having a causal relation with the familial ovarian cancer syndrome.

  7. Chemical synthesis, docking studies and biological effects of functionalized 1,3-diaryl-2-propen-1-ones on human colon cancer cells

    Directory of Open Access Journals (Sweden)

    Guo-Min Zhu


    Full Text Available A series of 1, 3-diaryl-2-propen-1-ones was synthesised in order to obtain a new type of anticancer drug, designed with hybrid features to inhibit colon cancer activated receptor. Based on computational modelling and docking studies, potential inhibitors were synthesised and their biological activity evaluated. The structures of newly synthesized compounds were confirmed by 1HNMR, 13CNMR and Mass spectrometry. All analogues were evaluated for in vitro cytotoxicity against human colon (caco-2 cancer cell lines. Compounds 1b, 1f-1h, and 2i showed significant cytotoxicity. Chalcones 1b, 1f and 1g were identified as the most potent and selective anticancer agents with IC50 values <1 µg/mL and 1.5 µg/mL, against caco-2 cell line, respectively. In conclusion, this finding confirms the suitability of indolyl chalcone analogues as candidates for further investigation towards the management of colon cancer related diseases.

  8. Regulatory effect of evodiamine on the malignant biological behaviors and Wnt/β-catenin signaling pathway of colorectal cancer cell lines HT29

    Directory of Open Access Journals (Sweden)

    Yuan-Hui Wang


    Full Text Available Objective: To study the regulatory effect of evodiamine on the malignant biological behaviors and Wnt/β-catenin signaling pathway of colorectal cancer cell lines HT29. Methods: Colorectal cancer cell lines HT29 were cultured and divided into blank control group and evodiamine group, and after different treatment, cell viability, proportion of different cell cycle as well as the contents of VEGFA, VEGFB, VEGFC, MMP3, MMP14, Wnt and β-catenin were detected. Results: (1 Cell viability: MTT value of evodiamine group was significantly lower than that of blank control group; (2 Cell cycle: proportion of both S phase and G2/M phase of evodiamine group were lower than those of blank control group, and proportion of G0/ G1 phase was higher than that of blank control group; (3 VEGF and MMP contents: VEGFA, VEGFB, VEGFC, MMP3 and MMP14 contents of evodiamine group were lower than those of blank control group; (4 Wnt/β-catenin signaling pathway: Wnt and β-catenin contents of evodiamine group were lower than those of blank control group. Conclusion: Evodiamine can inhibit the proliferation of colorectal cancer cell lines HT29 and down-regulate the expression of VEGF and MMP, and the effect may be achieved by inhibiting the activation of Wnt/β-catenin signaling pathway.

  9. 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


    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.

  10. Biological evaluation of a novel Herceptin-platinum (II) conjugate for efficient and cancer cell specific delivery. (United States)

    Huang, Rong; Sun, Yu; Zhang, Xiang-yang; Sun, Bai-wang; Wang, Qiu-cui; Zhu, Jin


    Platinum-based drugs have been widely used for the treatment of malignant tumors. However, their applications are limited by severe side effects for their lack of selectivity for cancer cells. The development of antibody drug conjugates (ADCs) have provided a platform to reduce drug toxicity and improve drug efficacy. Here we describe a nover conjugate comprising of Herceptin (an anti-HER2 antibody) and platinum drug via a cathepsin B cleavable dipetide for enhancing drug accumulation and HER2-positive cancer cell specific delivery. This conjugate is believed to be cleaved by cathepsin B, leading to a 1,6-elimination reaction and activation of drug release. Herceptin-Pt(II) is evaluated to have approximately loaded with 6.4 moles platinum drugs per mole of antibody. We demonstrate that Herceptin-Pt(II) retain high and selective binding affinity for HER2 protein and HER2-positive SK-BR-3 cancer cells. The in vitro cytotoxicity tests indicate that Herceptin-Pt(II) exhibits much higher cytotoxicity than oxaliplatin against SK-BR-3 cells. More importantly, Herceptin-Pt(II) shows no obvious inhibition against the growth of both MCF-7 and MDA-MB-231 cells, which express lower levels of HER2. Furthermore, compared with free oxaliplatin, Herceptin significantly improved the cellular uptake of platinum drugs in SK-BR-3 cells. In summary, Herceptin-platinum (II) conjugate is a remarkable and potent platform for efficient and cancer cell specific delivery. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

  11. 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


    -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...... tightly restricted ppGalNAc-T's may result in initiation of O-linked glycosylation at normally unoccupied potential glycosylation sites leading to altered glycoforms of proteins with changed biological activity which may contribute to the pathogenesis of cancer....... understood, may mediate the synthesis of varied glycoforms of cellular proteins with different biological activities. Disruptions in glycosylation are a common feature of cancer and may have functional significance. Immunocytochemistry with confocal scanning laser microscopy was employed to detect members...

  12. Mechanistic Effects of Calcitriol in Cancer Biology

    Directory of Open Access Journals (Sweden)

    Lorenza Díaz


    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.

  13. Overexpression of Pokemon in non-small cell lung cancer and foreshowing tumor biological behavior as well as clinical results. (United States)

    Zhao, Zhi-Hong; Wang, Sheng-Fa; Yu, Liang; Wang, Ju; Chang, Hao; Yan, Wei-Li; Zhang, Jian; Fu, Kai


    Transcription factor Pokemon, a central regulation gene of the important tumor suppressor alternative reading frame (ARF), exerted its activity by acting upstream of many tumor-suppressing genes and proto-oncogenes. Its expression in non-small cell lung cancer (NSCLC) and its clinical significance remains unclear. The aim of this study was to investigate the expression of Pokemon in non-small cell lung cancer and to explore its correlation with the clinical pathological characteristics and its influence on patients' prognosis. Observe the expression of Pokemon in NSCLC and investigate its mechanism and clinical significance. Determine the expression of Pokemon in human NSCLC cell lines as well as 55 cases of NSCLC tumor tissues, tumor adjacent tissues and surrounding tissues by reverse transcription-polymerase chain reaction (RT-PCR) and Western blot, and analyze the relationship between Pokemon expression in NSCLC tumor tissues and clinicopathological features. Determine 62 NSCLC tumor tissues (5 years ago) and p14(ARF) expression with immunohistochemical technique, discuss the correlation between them and assess the effect of Pokemon on prognosis of patients with lung cancer. Pokemon mRNA and protein took on high expression in lung cancer cell lines, and the expression difference between cancer tissues, tumor adjacent tissues and surrounding tissues had statistical significance (PPokemon expression and p14(ARF) expression were negatively correlated (r=-0.287). The expression of Pokemon was determined not to be associated with the patient's sex, age, smoking condition, tumor differentiation degree, histology and lymph node metastasis condition. However, its relationship with TNM staging was established (PPokemon expression was significantly higher than that of those with positive Pokemon expression (P=0.004), therefore, the expression of Pokemon is believed to be an independent factor affecting prognosis (P=0.034). There was high expression of Pokemon in NSCLC

  14. A systems biology analysis of autophagy in cancer therapy. (United States)

    Shi, Zheng; Li, Chun-yang; Zhao, Si; Yu, Yang; An, Na; Liu, Yong-xi; Wu, Chuan-fang; Yue, Bi-song; Bao, Jin-ku


    Autophagy, which degrades redundant or damaged cellular constituents, is intricately relevant to a variety of human diseases, most notably cancer. Autophagy exerts distinct effects on cancer initiation and progression, due to the intrinsic overlapping of autophagic and cancer signalling pathways. However, due to the complexity of cancer as a systemic disease, the fate of cancer cells is not decided by any one signalling pathway. Numerous autophagic inter-connectivity and cross-talk pathways need to be further clarified at a systems level. In this review, we propose a systems biology perspective for the comprehensive analysis of the autophagy-cancer network, focusing on systems biology analysis in autophagy and cancer therapy. Together, these analyses may not only improve our understanding on autophagy-cancer relationships, but also facilitate cancer drug discovery. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  15. Mechanotransduction in cancer stem cells. (United States)

    Hao, Jin; Zhang, Yueling; Ye, Rui; Zheng, Yingcheng; Zhao, Zhihe; Li, Juan


    The cancer stem cell (CSC) concept, which arose about a decade ago, proposes that tumor growth is sustained by a subpopulation of highly malignant cells. These cells, termed CSCs, are capable of extensive self-renewal that contributes to metastasis and treatment resistance. Therefore, therapeutic strategies that target CSCs should be developed for improving outcomes of cancer patients. Recent progress has highlighted the importance of physical properties of the extracellular matrix and mechanotransduction pathway in cancer cells during cancer development. On the other hand, the significance of CXCR1, an upstream signal of FAK/PI3K/Akt has been revealed in CSCs. FAK/PI3K/Akt is a key signal mediator in mechanotransduction pathway. Therefore, mechanotransduction could be a new target for CSCs, and would be an innovative way to treat cancer by inhibiting FAK/PI3K/Akt. © 2013 International Federation for Cell Biology.

  16. Cancer cell biology: a student-centered instructional module exploring the use of multimedia to enrich interactive, constructivist learning of science. (United States)

    Bockholt, Susanne M; West, J Paige; Bollenbacher, Walter E


    Multimedia has the potential of providing bioscience education novel learning environments and pedagogy applications to foster student interest, involve students in the research process, advance critical thinking/problem-solving skills, and develop conceptual understanding of biological topics. Cancer Cell Biology, an interactive, multimedia, problem-based module, focuses on how mutations in protooncogenes and tumor suppressor genes can lead to uncontrolled cell proliferation by engaging students as research scientists/physicians with the task of diagnosing the molecular basis of tumor growth for a group of patients. The process of constructing the module, which was guided by scientist and student feedback/responses, is described. The completed module and insights gained from its development are presented as a potential "multimedia pedagogy" for the development of other multimedia science learning environments.

  17. Cancer Cell Biology: A Student-Centered Instructional Module Exploring the Use of Multimedia to Enrich Interactive, Constructivist Learning of Science (United States)

    Bockholt, Susanne M.; West, J. Paige; Bollenbacher, Walter E.


    Multimedia has the potential of providing bioscience education novel learning environments and pedagogy applications to foster student interest, involve students in the research process, advance critical thinking/problem-solving skills, and develop conceptual understanding of biological topics. Cancer Cell Biology, an interactive, multimedia, problem-based module, focuses on how mutations in protooncogenes and tumor suppressor genes can lead to uncontrolled cell proliferation by engaging students as research scientists/physicians with the task of diagnosing the molecular basis of tumor growth for a group of patients. The process of constructing the module, which was guided by scientist and student feedback/responses, is described. The completed module and insights gained from its development are presented as a potential “multimedia pedagogy” for the development of other multimedia science learning environments. PMID:12822037

  18. Circadian rhythm disruption in cancer biology. (United States)

    Savvidis, Christos; Koutsilieris, Michael


    Circadian rhythms show universally a 24-h oscillation pattern in metabolic, physiological and behavioral functions of almost all species. This pattern is due to a fundamental adaptation to the rotation of Earth around its own axis. Molecular mechanisms of generation of circadian rhythms organize a biochemical network in suprachiasmatic nucleus and peripheral tissues, building cell autonomous clock pacemakers. Rhythmicity is observed in transcriptional expression of a wide range of clock-controlled genes that regulate a variety of normal cell functions, such as cell division and proliferation. Desynchrony of this rhythmicity seems to be implicated in several pathologic conditions, including tumorigenesis and progression of cancer. In 2007, the International Agency for Research on Cancer (IARC) categorized "shiftwork that involves circadian disruption [as] probably carcinogenic to humans" (Group 2A in the IARC classification system of carcinogenic potency of an agentagent) (Painting, Firefighting, and Shiftwork; IARC; 2007). This review discusses the potential relation between disruptions of normal circadian rhythms with genetic driving machinery of cancer. Elucidation of the role of clockwork disruption, such as exposure to light at night and sleep disruption, in cancer biology could be important in developing new targeted anticancer therapies, optimizing individualized chronotherapy and modifying lighting environment in workplaces or homes.

  19. Paradoxical roles of dual oxidases in cancer biology. (United States)

    Little, Andrew C; Sulovari, Arvis; Danyal, Karamatullah; Heppner, David E; Seward, David J; van der Vliet, Albert


    Dysregulated oxidative metabolism is a well-recognized aspect of cancer biology, and many therapeutic strategies are based on targeting cancers by altering cellular redox pathways. The NADPH oxidases (NOXes) present an important enzymatic source of biological oxidants, and the expression and activation of several NOX isoforms are frequently dysregulated in many cancers. Cell-based studies have demonstrated a role for several NOX isozymes in controlling cell proliferation and/or cell migration, further supporting a potential contributing role for NOX in promoting cancer. While various NOX isoforms are often upregulated in cancers, paradoxical recent findings indicate that dual oxidases (DUOXes), normally prominently expressed in epithelial lineages, are frequently suppressed in epithelial-derived cancers by epigenetic mechanisms, although the functional relevance of such DUOX silencing has remained unclear. This review will briefly summarize our current understanding regarding the importance of reactive oxygen species (ROS) and NOXes in cancer biology, and focus on recent observations indicating the unique and seemingly opposing roles of DUOX enzymes in cancer biology. We will discuss current knowledge regarding the functional properties of DUOX, and recent studies highlighting mechanistic consequences of DUOX1 loss in lung cancer, and its consequences for tumor invasiveness and current anticancer therapy. Finally, we will also discuss potentially unique roles for the DUOX maturation factors. Overall, a better understanding of mechanisms that regulate DUOX and the functional consequences of DUOX silencing in cancer may offer valuable new diagnostic insights and novel therapeutic opportunities. Copyright © 2017 Elsevier Inc. All rights reserved.

  20. Advances in molecular biology of lung disease: aiming for precision therapy in non-small cell lung cancer. (United States)

    Rooney, Claire; Sethi, Tariq


    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.

  1. Phenomenon of PDT-induced post-irradiation apoptosis in biological liquids cancer cells using sulphonated phthalocyanine aluminum photosensitizer (United States)

    Douplik, Alexandre Y.; Loschenov, Victor B.; Vorozhtsov, Georgy N.; Kogan, Eugenia A.; Kusin, Michael; Ablitsov, Y.; Ilyina, O. S.


    Discovered during last year's phenomenon of PDT-induced apoptosis (programmed cell destruction) in cell culture immediately after light irradiation using phthalocyanine photosensitizers can be used for treatment of cancer. Experiments were carried out on mice with ascites. Ascitic liquid with the added photosensitizer was irradiated by light source with wavelength 660 - 680 nm and used according to ex vivo procedure. Actuation and development of apoptosis process in ascitic liquid were estimated by cytomorphological tests. It has been observed the phenomenon of growth of relative fraction of cells damage level expressed mainly as apoptosis after PDT procedure ex vivo. We suggest to call this phenomenon as PDT-induced post-irradiation apoptosis (PIP- apoptosis). Dependence between level of expressing of PIP- apoptosis and sulphonated phthalocyanine aluminum photosensitizer (Photosense) concentration at used photosensitizer concentrations has not been found out.

  2. Regulating Cancer Associated Fibroblast Biology in Prostate Cancer (United States)


    SUPPLEMENTARY NOTES 14. ABSTRACT There is an urgent need to develop both new approaches to the treatment of prostate cancer. Analysis of human prostate...AWARD NUMBER: W81XWH-15-1-0512 TITLE: Regulating Cancer-Associated Fibroblast Biology in Prostate Cancer PRINCIPAL INVESTIGATOR: Andrew...CONTRACT NUMBER Regulating Cancer-Associated Fibroblast Biology in Prostate Cancer 5b. GRANT NUMBER W81XWH-15-1-0512 5c. PROGRAM ELEMENT NUMBER 6

  3. Measuring cell identity in noisy biological systems (United States)

    Birnbaum, Kenneth D.; Kussell, Edo


    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 measure dSpec, which measures the effect of noise on specificity. Using global gene expression data from the mouse brain, plant root and human white blood cells, we show that Spec identifies genes with variable expression levels that are nonetheless highly specific of particular cell types. When samples from different individuals are used, dSpec measures genes’ transcriptional plasticity in each cell type. Our approach is broadly applicable to mapped gene expression measurements in stem cell biology, developmental biology, cancer biology and biomarker identification. As an example of such applications, we show that Spec identifies a new class of biomarkers, which exhibit variable expression without compromising specificity. The approach provides a unifying theoretical framework for quantifying specificity in the presence of noise, which is widely applicable across diverse biological systems. PMID:21803789

  4. The cell biology of taste (United States)


    Taste buds are aggregates of 50–100 polarized neuroepithelial cells that detect nutrients and other compounds. Combined analyses of gene expression and cellular function reveal an elegant cellular organization within the taste bud. This review discusses the functional classes of taste cells, their cell biology, and current thinking on how taste information is transmitted to the brain. PMID:20696704

  5. Synthesis of Scutellarein Derivatives with a Long Aliphatic Chain and Their Biological Evaluation against Human Cancer Cells

    Directory of Open Access Journals (Sweden)

    Guanghui Ni


    Full Text Available Scutellarin is the major active flavonoid extracted from the traditional Chinese herbal medicine Erigeron breviscapus (Vant. Hand-Mazz., which is widely used in China. Recently, accumulating evidence has highlighted the potential role of scutellarin and its main metabolite scutellarein in the treatment of cancer. To explore novel anticancer agents with high efficiency, a series of new scutellarein derivatives with a long aliphatic chain were synthesized, and the antiproliferative activities against Jurkat, HCT-116 and MDA-MB-231 cancer cell lines were assessed. Among them, compound 6a exhibited the strongest antiproliferative effects on Jurkat (IC50 = 1.80 μM, HCT-116 (IC50 = 11.50 μM and MDA-MB-231 (IC50 = 53.91 μM. In particular, 6a even showed stronger antiproliferative effects than the positive control NaAsO2 on Jurkat and HCT-116 cell lines. The results showed that a proper long aliphatic chain enhanced the antiproliferative activity of scutellarein.

  6. Lung cancer - small cell (United States)

    ... carcinoma Small cell carcinoma Squamous cell carcinoma Secondhand smoke and lung cancer Normal lungs and alveoli Respiratory system Smoking hazards Bronchoscope References Horn L, Eisenberg R, ...

  7. Cell phones and cancer (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 exposure ...

  8. Mechanics rules cell biology

    Directory of Open Access Journals (Sweden)

    Wang James HC


    Full Text Available Abstract Cells in the musculoskeletal system are subjected to various mechanical forces in vivo. Years of research have shown that these mechanical forces, including tension and compression, greatly influence various cellular functions such as gene expression, cell proliferation and differentiation, and secretion of matrix proteins. Cells also use mechanotransduction mechanisms to convert mechanical signals into a cascade of cellular and molecular events. This mini-review provides an overview of cell mechanobiology to highlight the notion that mechanics, mainly in the form of mechanical forces, dictates cell behaviors in terms of both cellular mechanobiological responses and mechanotransduction.

  9. Cancer Stem Cells and the Ontogeny of Lung Cancer


    Peacock, Craig D.; Watkins, D. Neil


    Lung cancer is the leading cause of cancer death in the world today and is poised to claim approximately 1 billion lives during the 21st century. A major challenge in treating this and other cancers is the intrinsic resistance to conventional therapies demonstrated by the stem/progenitor cell that is responsible for the sustained growth, survival, and invasion of the tumor. Identifying these stem cells in lung cancer and defining the biologic processes necessary for their existence is paramou...

  10. Molecular biology of the cell

    National Research Council Canada - National Science Library

    Alberts, Bruce; Walter, Peter; Raff, Martin; Roberts, Keith; Lewis, Julian; Johnson, Alexander


    .... By extracting fundamental concepts and meaning 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...

  11. Molecular biology of the cell

    CERN Document Server

    Alberts, Bruce; Lewis, Julian


    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...

  12. Phytochemical Study of the Genus Salpichroa (Solanaceae), Chemotaxonomic Considerations, and Biological Evaluation in Prostate and Breast Cancer Cells. (United States)

    Basso, Ana Valentina; Leiva González, Segundo; Barboza, Gloria Estela; Careaga, Valeria Pilar; Calvo, Juan Carlos; Sacca, Paula A; Nicotra, Viviana Estela


    Twelve Salpichroa taxa have been phytochemically analyzed. From the aerial parts of S. scandens, four known salpichrolides A, C, I, S, and an unreported withanolide named salpichrolide V (1), were isolated. In S. dependens, S. gayi, S. glandulosa subsp. glandulosa, S. glandulosa subps. weddellii, S. leucantha, S. micrantha, S. microloba, S. proboscidea, S. ramosissima, S. tristis var. tristis, and S. weberbauerii, no withanolides were found. The chemical content of ca. 85% of the Salpichroa taxa is in agreement with molecular studies, which suggest that Salpichroa and Jaborosa, a genus considered morphologically close to Salpichroa, are distant in the systematic of the Solanoideae subfamily. Moreover, the in vitro cytotoxic activity of a set of natural salpichrolides and derivatives was examined against two prostate carcinoma cell lines (PC3 and LNCaP) and two human breast cancer cell lines (MCF-7 and T47D). Several compounds showed moderate activity (IC 50  = 64.91 - 29.97 μm). © 2017 Wiley-VHCA AG, Zurich, Switzerland.

  13. Helveticoside is a biologically active component of the seed extract of Descurainia sophia and induces reciprocal gene regulation in A549 human lung cancer cells. (United States)

    Kim, Bu-Yeo; Lee, Jun; Kim, No Soo


    Although the pharmacological activities of the seed extract of Descurainia sophia have been proven to be useful against cough, asthma, and edema, the biologically active components, particularly at the molecular level, remain elusive. Therefore, we aimed to identify the active component of an ethanol extract of D. sophia seeds (EEDS) by applying a systematic genomic approach. After treatment with EEDS, the dose-dependently expressed genes in A549 cells were used to query the Connectivity map to determine which small molecules could closely mimic EEDS in terms of whole gene expression. Gene ontology and pathway analyses were also performed to identify the functional involvement of the drug responsive genes. In addition, interaction network and enrichment map assays were implemented to measure the functional network structure of the drug-responsive genes. A Connectivity map analysis of differentially expressed genes resulted in the discovery of helveticoside as a candidate drug that induces a similar gene expression pattern to EEDS. We identified the presence of helveticoside in EEDS and determined that helveticoside was responsible for the dose-dependent gene expression induced by EEDS. Gene ontology and pathway analyses revealed that the metabolism and signaling processes in A549 cells were reciprocally regulated by helveticoside and inter-connected as functional modules. Additionally, in an ontological network analysis, diverse cancer type-related genes were found to be associated with the biological functions regulated by helveticoside. Using bioinformatic analyses, we confirmed that helveticoside is a biologically active component of EEDS that induces reciprocal regulation of metabolism and signaling processes. Our approach may provide novel insights to the herbal research field for identifying biologically active components from extracts.

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

    DEFF Research Database (Denmark)

    Bjerregaard, B; Holck, Susanne; Christensen, Ib Jarle


    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...... and inhibits fusions between breast cancer cells and endothelial cells. Moreover, a syncytin inhibitory peptide also inhibits fusions between cancer and endothelial cells. These results are the first to show that syncytin is expressed by human cancer cells and is involved in cancer-endothelial cell fusions....

  15. Understanding Cancer Prognosis

    Medline Plus

    Full Text Available ... Cancer Kidney (Renal Cell) Cancer Leukemia Liver Cancer Lung Cancer Lymphoma Pancreatic Cancer Prostate Cancer Skin Cancer Thyroid ... Cancer Biology Research Cancer Genomics Research Research on Causes of Cancer Cancer Diagnosis Research Cancer Prevention Research ...

  16. Understanding Cancer Prognosis

    Medline Plus

    Full Text Available ... Cancer Colorectal Cancer Kidney (Renal Cell) Cancer Leukemia Liver Cancer Lung Cancer Lymphoma Pancreatic Cancer Prostate Cancer Skin ... Cancer Biology Research Cancer Genomics Research Research on Causes of Cancer Cancer Diagnosis Research Cancer Prevention Research ...

  17. Harnessing the apoptotic programs in cancer stem-like cells. (United States)

    Wang, Ying-Hua; Scadden, David T


    Elimination of malignant cells is an unmet challenge for most human cancer types even with therapies targeting specific driver mutations. Therefore, a multi-pronged strategy to alter cancer cell biology on multiple levels is increasingly recognized as essential for cancer cure. One such aspect of cancer cell biology is the relative apoptosis resistance of tumor-initiating cells. Here, we provide an overview of the mechanisms affecting the apoptotic process in tumor cells emphasizing the differences in the tumor-initiating or stem-like cells of cancer. Further, we summarize efforts to exploit these differences to design therapies targeting that important cancer cell population. © 2015 The Authors.

  18. Developmental biology, the stem cell of biological disciplines. (United States)

    Gilbert, Scott F


    Developmental biology (including embryology) is proposed as "the stem cell of biological disciplines." Genetics, cell biology, oncology, immunology, evolutionary mechanisms, neurobiology, and systems biology each has its ancestry in developmental biology. Moreover, developmental biology continues to roll on, budding off more disciplines, while retaining its own identity. While its descendant disciplines differentiate into sciences with a restricted set of paradigms, examples, and techniques, developmental biology remains vigorous, pluripotent, and relatively undifferentiated. In many disciplines, especially in evolutionary biology and oncology, the developmental perspective is being reasserted as an important research program.

  19. Liver Cancer Stem Cells


    Sameh Mikhail; Aiwu Ruth He


    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...

  20. Molecular biology in colorectal cancer. (United States)

    Benito, Manuel; Díaz-Rubio, Eduardo


    Cancer is a genetic disease. Colorectal cancer is probably the type of cancer for which the most is known about the genes affected by cancer-causing mutations, their normal functions and their carcinogenic effects when mutated. Most cancer-causing mutations are somatic, occurring in the affected tissue during the course of carcinogenesis. However, most cancers also have a hereditary component that is caused by predisposing mutations that affect the germline, are heritable and contribute to the initiation of carcinogenesis. High-penetrance mutations confer predisposition to colorectal cancer mainly in Lynch syndrome (which involves mutations in mismatch-repair genes) and in familial adenomatous polyposis (which involves mutations in the APC tumour suppressor). Together, these conditions account for 5% or less of all cases of colorectal cancer. Low-penetrance mutations account for a high proportion of all the attributable risk of colorectal cancer, in both familial and sporadic cases. These mutations are more difficult to identify, but mainly due to the implementation of association studies, are increasingly being detected and characterized. The identification of both high- and low-penetrance mutations contributes significantly to our understanding of the molecular genetic processes occurring in cancer. This understanding facilitates the development of therapeutic drugs and preventive strategies.

  1. Cancer stem cell metabolism

    National Research Council Canada - National Science Library

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


    .... 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...

  2. Adenovirus platform enhances transduction efficiency of human mesenchymal stem cells: An opportunity for cellular carriers of targeted TRAIL-based TR3 biologics in ovarian cancer.

    Directory of Open Access Journals (Sweden)

    Lindsay M Kuroki

    Full Text Available Clinical application of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL-based cancer therapeutics has not reached optimal potencies in part due to inadequate drug stability and inefficiencies in cancer-selective drug delivery. As such, innovative strategies regarding drug design and delivery are of utmost importance to achieve improved treatment results. With our current study, we aimed at exploring the groundwork for a two-stage targeting concept, which is based on the intrinsic tumor homing capacity of mesenchymal stem cells (MSCs as cellular drug factories for the in situ production of our newly designed and biomarker-targeted TRAIL-based TR3 therapeutics. Since MSCs are primary cells, capable in vitro of only a limited number of cell divisions, identification of suitable strategies for their efficient genetic manipulation is of critical importance. We chose adenoviral (Ad vectors as a transduction vehicle due to its ability to infect dividing and non-dividing cells and because of their limited restrictions regarding the packaging capacity of their genetic payload. In order to enhance the transduction efficacy of MSCs using Ad5 wild-type-based vectors, we tested a variety of fiber knob modifications on a panel of patient-derived MSC lines established from adipose tissue. We identified Ad5pK7, an Ad5 vector containing a polylysine fiber knob modification, exhibiting the highest transduction rates across a panel of 16 patient-derived MSC lines. We further demonstrated that MSCs could be efficiently transduced with an Ad5pK7 vector containing membrane-anchored and secreted TR3 expression units, including the MUC16 (CA125-targeted variant Meso64-TR3. In both in vitro and in vivo experiments, MSC-derived Meso64-TR3 was far more potent on MUC16-expressing ovarian cancer compared to its non-targeted TR3 counterpart. Our findings thus provide the foundation to initiate further preclinical investigations on MSC-mediated treatment

  3. Colon Cancer Cell Separation by Dielectrophoresis (United States)

    Yang, Fang; Yang, Xiaoming; Jiang, H.; Wood, P.; Hrushesky, W.; Wang, Guiren


    Separation of cancer cells from the other biological cells can be useful for clinical cancer diagnosis and cancer treatment. In this presentation, conventional dielectrophoresis (c-DEP) is used in a microfluidic chip to manipulate and collect colorectal cancer HCT116 cell, which is doped with Human Embryonic Kidney 293 cells (HEK 293). It is noticed that, the HCT116 cell are deflected to a side channel from a main channel clearly by apply electric field at particular AC frequency band. This motion caused by negative DEP can be used to separate the cancer cell from others. In this manuscript, chip design, flow condition, the DEP spectrum of the cancer cell are reported respectively, and the separation and collection efficiency are investigated as well. The sorter is microfabricated using plastic laminate technology. -/abstract- This work has been financially supported by the NSF RII funding (EP

  4. 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


    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.

  5. Cancer and Aging: A Complex Biological Association. (United States)

    Navarrete-Reyes, Ana Patricia; Soto-Pérez-de-Celis, Enrique; Hurria, Arti


    Cancer is one of the leading causes of death in both developing and developed countries. It is also a particularly significant health problem in older populations since half of all malignancies occur in patients aged 70 years or older. Cancer is a disease of aging, and as such there is a strong biological association between the mechanisms of aging and carcinogenesis. During the past few decades, mechanisms of aging exerting pro- and anti-oncogenic effects have been described, and the role of these mechanisms in cancer treatment and prognosis is currently being investigated. In this review we describe the different theories of aging and the evidence on the biological link between these mechanisms and carcinogenesis. Additionally, we review the implications of the biology of aging on the treatment and prognosis of older adults with cancer, and the opportunities for translational research into biomarkers of aging in this patient population.

  6. Crispoic acid, a new compound from Laelia marginata (Orchidaceae), and biological evaluations against parasites, human cancer cell lines and Zika virus. (United States)

    Belloto, Andrezza C; Souza, Gredson K; Perin, Paula C; Schuquel, Ivania T A; Santin, Silvana M O; Chiavelli, Lucas U R; Garcia, Francielle P; Kaplum, Vanessa; Rodrigues, Jean H S; Scariot, Débora B; Delvecchio, Rodrigo; Machado-Ferreira, Erik; Santana Aguiar, Renato; Soares, Carlos A G; Nakamura, Celso V; Pomini, Armando M


    The phytochemical study of Laelia marginata (Lindl.) L. O. Williams (Orchidaceae) led to the isolation of a new natural product named crispoic acid (1), together with six other known compounds (2-7). The new natural product was identified as a dimer of eucomic acid and was structurally characterised based upon 1D and 2D NMR and HRMS data. Biological assays with plant crude extract, fractions and isolated compounds were performed against two human cancer cell lines (Hela and Siha), and the tropical parasites Trypanosoma cruzi and Leishmania (Leishmania) amazonensis. The phenantrenoid 9,10-dihydro-4-methoxyphenanthren-2,7-diol 2 was active against Hela and Siha cells (CC 50 5.86 ± 0.19 and 20.78 ± 2.72 μg/mL, respectively). Sub-lethal concentrations of the flavone rhamnazin 4 were not able to rescue the viability of the Vero cells infected by Zika virus.

  7. Revealing the Functions of Tenascin-C in 3-D Breast Cancer Models Using Cell Biological and in Silico Approaches

    National Research Council Canada - National Science Library

    Tarasevicuite, Agne


    The extracellular matrix (ECM) glycoprotein tenascin-C (TN-C) is induced in the breast stroma, where it is associated with both breast cancer development and progression, yet its role in this disease remains obscure...

  8. Pathological and biological aspects of colorectal cancer treatment

    NARCIS (Netherlands)

    Gosens, Marleen Johanna Elisabeth Maria


    Pathological and biological aspects of colorectal cancer treatment. This thesis describes several pathological and biological aspects of colorectal cancer treatment. Different patient populations were investigated including patients with mobile rectal cancer enrolled in the Dutch TME trial, patients

  9. Basal cell cancer (image) (United States)

    ... biopsy is needed to prove the diagnosis of basal cell carcinoma. Treatment varies depending on the size, depth, and location of the cancer. Early treatment by a dermatologist may result in a cure ... is required to watch for new sites of basal cell cancer.

  10. Prostate cancer stem cells. (United States)

    Tu, Shi-Ming; Lin, Sue-Hwa


    Stem cells have long been implicated in prostate gland 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 androgen receptor-negative (AR(-)) status of prostate stem cells renders them inherently insensitive to androgen blockade therapy. The androgen-regulated gene fusion TMPRSS2-ERG could be used to clarify both the cells of origin and the evolution of prostate cancer cells. In this review, we show that the hypothesis that distinct subtypes of cancer result from abnormalities within specific cell types-the stem cell theory of cancer-may instigate a major paradigm shift in cancer research and therapy. Ultimately, the stem cell theory of cancers will affect how we practice clinical oncology: our diagnosis, monitoring, and therapy of prostate and other cancers. Copyright © 2012 Elsevier Inc. All rights reserved.

  11. Stochastic processes in cell biology

    CERN Document Server

    Bressloff, Paul C


    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...

  12. Biological fuel cells and their applications


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


    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...

  13. Biological evaluation of bismuth non-steroidal anti-inflammatory drugs (BiNSAIDs): stability, toxicity and uptake in HCT-8 colon cancer cells. (United States)

    Hawksworth, Emma L; Andrews, Philip C; Lie, Wilford; Lai, Barry; Dillon, Carolyn T


    Recent studies showed that the metal-coordinated non-steroidal anti-inflammatory drug (NSAID), copper indomethacin, reduced aberrant crypt formation in the rodent colon cancer model, while also exhibiting gastrointestinal sparing properties. In the present study, the stability and biological activity of three BiNSAIDs of the general formula [Bi(L)3]n, where L=diflunisal (difl), mefenamate (mef) or tolfenamate (tolf) were examined. NMR spectroscopy of high concentrations of BiNSAIDs (24h in cell medium, 37°C) indicated that their structural stability and interactions with cell medium components were NSAID specific. Assessment of cell viability using the [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium]bromide (MTT) assay showed that the toxicity ranking of the BiNSAIDs paralleled those of the respective free NSAIDs: diflHbismuth content was observed following treatment with [Bi(tolf)3]. Since NMR studies indicated that [Bi(tolf)3] was the most stable BiNSAID and that cellular uptake of bismuth correlated with structural stability it appears that bismuth uptake is assisted by the NSAID. Microprobe SR-XRF imaging showed that the intracellular fate of bismuth was independent of the specific BiNSAID treatment whereby all BiNSAID-treated cells showed bismuth accumulation in the cytoplasm within 24-h exposure. The size and location of the hot spots (0.3-5.8μm(2)), were consistent with cellular organelles such as lysosomes. Copyright © 2014 Elsevier Inc. All rights reserved.

  14. Trioorganotin compounds, cognate ligands, of nuclear retinoid X receptors - biological effects in human breats cancer cell lines

    Czech Academy of Sciences Publication Activity Database

    Brtko, J.; Toporová, L.; Macejová, D.; Hunáková, L.; Bobálová, Janette


    Roč. 10, suppl. 1 (2017), s. 19-19 ISSN 1337-6853. [Mezioborová toxikologická konference /22./ TOXCON 2017. 21.06.2017-23.06.2017, Plzeň] Grant - others:AV ČR(CZ) SAV-15-01 Program:Bilaterální spolupráce Institutional support: RVO:68081715 Keywords : receptor * organotin compounds * cancer

  15. Breast cancer stem cells

    Directory of Open Access Journals (Sweden)

    Thomas W Owens


    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.

  16. The clinical and biological implications of the focal adhesion kinase pathway in ShenLingLan mediated suppression of cellular migration of ovarian cancer cells

    Directory of Open Access Journals (Sweden)

    Owen S


    Full Text Available The incidence of ovarian cancer in the UK has increased by almost twenty percent since the 1970’s and the majority of cases are not diagnosed until the late stages, when metastasis is more likely to have occurred. Focal Adhesion Kinase (FAK is one of the key protein complexes which is integral to cell migration and has been linked to a variety of solid tumours. ShenLingLan (SLDM is a traditional herbal medicine which has been formulated for the treatment of solid tumours. This study aimed to establish the impact of SLDM on FAK in ovarian cancer cells in vitro and transcript levels of FAK in an ovarian cancer cohort. FAK and paxillin phosphorylation events stimulated by SLDM treatment were identified using a Kinexus™ antibody based protein array. The impact of SLDM on cell attachment and migration was evaluated using Electric cell-substrate impedance sensing (ECIS, whilst the changes in focal adhesion complex localisation were assessed using immunofluorescence. In an ovarian cancer cohort, differences in FAK and paxillin transcript levels were assessed against key clinical parameters such as differentiation, stage and survival outcome. SLDM treatment of ovarian cancer cells in vitro resulted in the suppression of FAK and paxillin phosphorylation at several sites, which appeared to manifest as decreased cellular attachment and migration in a range of immortalised ovarian cancer cells. Increased FAK and paxillin transcript copies were observed in high grade and poorly differentiated ovarian tumours as well as in tumours from patients with ovarian cancer related incidence. SLDM has a profound effect on the migratory and adhesive properties of ovarian cancer cells, potentially via inhibitory effects on the activation of the FAK pathway, which is aberrant in clinical ovarian cancers.

  17. Biological resonance for cancer metastasis, a new hypothesis based on comparisons between primary cancers and metastases. (United States)

    Gao, Dongwei; Li, Sha


    Many hypotheses have been proposed to try to explain cancer metastasis. However, they seem to be contradictory and have some limitations. Comparisons of primary tumors and matched metastases provide new insight into metastasis. The results show high concordances and minor differences at multiple scales from organic level to molecular level. The concordances reflect the commonality between primary cancer and metastasis, and also mean that metastatic cancer cells derived from primary cancer are quite conservative in distant sites. The differences reflect variation that cancer cells must acquire new traits to adapt to foreign milieu during the course of evolving into a new tumor in second organs. These comparisons also provided new information on understanding mechanism of vascular metastasis, organ-specific metastasis, and tumor dormancy. The collective results suggest a new hypothesis, biological resonance (bio-resonance) model. The hypothesis has two aspects. One is that primary cancer and matched metastasis have a common progenitor. The other is that both ancestors of primary cancer cells and metastatic cancer cells are under similar microenvironments and receive similar or same signals. When their interactions reach a status similar to primary cancer, metastasis will occur. Compared with previous hypotheses, the bio-resonance hypothesis seems to be more applicable for cancer metastasis to explain how, when and where metastasis occurs. Thus, it has important implications for individual prediction, prevention and treatment of cancer metastasis.

  18. Laboratory of Cell and Molecular Biology (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...

  19. Hurthle Cell Cancer (United States)

    ... breath Hurthle cell cancer Symptoms & causes Diagnosis & treatment Advertisement Mayo Clinic does not endorse companies or products. ... a Job Site Map About This Site Twitter Facebook Google YouTube Pinterest Mayo Clinic is a not- ...

  20. Basal cell skin cancer (United States)

    Basal cell skin cancer almost never spreads. If it is left untreated, it may spread into surrounding areas and nearby tissues and bone. In these cases, treatment can injure the appearance of the skin.

  1. Genetics and biological markers in urachal cancer. (United States)

    Behrendt, Mark A; van Rhijn, Bas W G


    Urachal cancer (UraC) is a rare tumor entity that usually develops at the basis of the remnant embryologic urachus. Consisting of mostly adenocarcinomas, most patients present with secondary symptoms due to an advanced stage with urinary bladder infiltration. One third of patients are already metastasized at presentation rendering them unsuitable for curative surgical treatment. In order to improve staging, treatment and follow-up, adequate knowledge about the genetic origin and potential markers is necessary. This paper reviews the English literature until December 2015. Pathologists argue for and against metaplasia or remnant enteric cells as origin for the adenomatous tissue found in UraC. Mutations in KRAS, BRAF, GNAS and Her2 have been associated with UraC. Immunohistochemical (IHC) markers like CEA, 34βE12, Claudin-18 and RegIV are indicative for mucous producing UraC. So far, IHC markers fail as prognosticators when matched to clinical data. Little is known about serum markers for UraC. CEA, CA19-9, CA125 and CA724 are mentioned as being elevated in UraC by some reports. Regarding the literature for biological markers in UraC, knowledge is mostly derived from case reports or cohort studies mentioning markers or predictors. More genetic research is needed to show whether UraC stems from progenitor cells of the cloaca or is due to metaplasia of transitional cells. Few IHC markers have shown indicative potential for UraC. A useful panel for differential diagnostics and clinicopathologic prognostication needs to be developed. Serum markers show very little potential for neither diagnosis nor follow-up in UraC. Further research on larger cohorts is necessary.

  2. Cancer systems biology: signal processing for cancer research (United States)

    Yli-Harja, Olli; Ylipää, Antti; Nykter, Matti; Zhang, Wei


    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. PMID:21439242

  3. Cancer systems biology and modeling: microscopic scale and multiscale approaches. (United States)

    Masoudi-Nejad, Ali; Bidkhori, Gholamreza; Hosseini Ashtiani, Saman; Najafi, Ali; Bozorgmehr, Joseph H; Wang, Edwin


    Cancer has become known as a complex and systematic disease on macroscopic, mesoscopic and microscopic scales. Systems biology employs state-of-the-art computational theories and high-throughput experimental data to model and simulate complex biological procedures such as cancer, which involves genetic and epigenetic, in addition to intracellular and extracellular complex interaction networks. In this paper, different systems biology modeling techniques such as systems of differential equations, stochastic methods, Boolean networks, Petri nets, cellular automata methods and agent-based systems are concisely discussed. We have compared the mentioned formalisms and tried to address the span of applicability they can bear on emerging cancer modeling and simulation approaches. Different scales of cancer modeling, namely, microscopic, mesoscopic and macroscopic scales are explained followed by an illustration of angiogenesis in microscopic scale of the cancer modeling. Then, the modeling of cancer cell proliferation and survival are examined on a microscopic scale and the modeling of multiscale tumor growth is explained along with its advantages. Copyright © 2014 Elsevier Ltd. All rights reserved.

  4. Designer nanoparticle: nanobiotechnology tool for cell biology (United States)

    Thimiri Govinda Raj, Deepak B.; Khan, Niamat Ali


    This article discusses the use of nanotechnology for subcellular compartment isolation and its application towards subcellular omics. This technology review significantly contributes to our understanding on use of nanotechnology for subcellular systems biology. Here we elaborate nanobiotechnology approach of using superparamagnetic nanoparticles (SPMNPs) optimized with different surface coatings for subcellular organelle isolation. Using pulse-chase approach, we review that SPMNPs interacted differently with the cell depending on its surface functionalization. The article focuses on the use of functionalized-SPMNPs as a nanobiotechnology tool to isolate high quality (both purity and yield) plasma membranes and endosomes or lysosomes. Such nanobiotechnology tool can be applied in generating subcellular compartment inventories. As a future perspective, this strategy could be applied in areas such as immunology, cancer and stem cell research.

  5. SU-C-202-04: Adapting Biologically Optimized Dose Escalation Based On Mid-Treatment PET/CT for Non-Small-Cell Lung Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, P; Kuo, L; Yorke, E; Hu, Y; Lockney, N; Mageras, G; Deasy, J; Rimner, A [Memorial Sloan Kettering Cancer Center, New York, NY (United States)


    Purpose: To develop a biological modeling strategy which incorporates the response observed on the mid-treatment PET/CT into a dose escalation design for adaptive radiotherapy of non-small-cell lung cancer. Method: FDG-PET/CT was acquired midway through standard fractionated treatment and registered to pre-treatment planning PET/CT to evaluate radiation response of lung cancer. Each mid-treatment PET voxel was assigned the median SUV inside a concentric 1cm-diameter sphere to account for registration and imaging uncertainties. For each voxel, the planned radiation dose, pre- and mid-treatment SUVs were used to parameterize the linear-quadratic model, which was then utilized to predict the SUV distribution after the full prescribed dose. Voxels with predicted post-treatment SUV≥2 were identified as the resistant target (response arm). An adaptive simultaneous integrated boost was designed to escalate dose to the resistant target as high as possible, while keeping prescription dose to the original target and lung toxicity intact. In contrast, an adaptive target volume was delineated based only on the intensity of mid-treatment PET/CT (intensity arm), and a similar adaptive boost plan was optimized. The dose escalation capability of the two approaches was compared. Result: Images of three patients were used in this planning study. For one patient, SUV prediction indicated complete response and no necessary dose escalation. For the other two, resistant targets defined in the response arm were multifocal, and on average accounted for 25% of the pre-treatment target, compared to 67% in the intensity arm. The smaller response arm targets led to a 6Gy higher mean target dose in the adaptive escalation design. Conclusion: This pilot study suggests that adaptive dose escalation to a biologically resistant target predicted from a pre- and mid-treatment PET/CT may be more effective than escalation based on the mid-treatment PET/CT alone. More plans and ultimately clinical

  6. Biological Activity of Carbazole Alkaloids and Essential Oil of Murraya koenigii Against Antibiotic Resistant Microbes and Cancer Cell Lines

    Directory of Open Access Journals (Sweden)

    Thilahgavani Nagappan


    Full Text Available A total of three carbazole alkaloids and essential oil from the leaves of Murraya koenigii (Rutaceae were obtained and examined for their effects on the growth of five antibiotic resistant pathogenic bacteria and three tumor cell lines (MCF-7, P 388 and Hela. The structures of these carbazoles were elucidated based on spectroscopy data and compared with literature data, hence, were identified as mahanine (1, mahanimbicine (2 and mahanimbine (3. The chemical constituents of the essential oil were identified using Gas Chromatography-Mass Spectroscopy (GCMS. These compounds exhibited potent inhibition against antibiotic resistant bacteria such as Staphylococcus aureus (210P JTU, Psedomonas aeruginosa (ATCC 25619, Klebsiella pneumonia (SR1-TU, Escherchia coli (NI23 JTU and Streptococcus pneumoniae (SR16677-PRSP with significant minimum inhibition concentration (MIC values (25.0–175.0 mg/mL and minimum bacteriacidal concentrations (MBC (100.0–500.0 mg/mL. The isolated compounds showed significant antitumor activity against MCF-7, Hela and P388 cell lines. Mahanimbine (3 and essential oil in particular showed potent antibacteria and cytotoxic effect with dose dependent trends (≤5.0 μg/mL. The findings from this investigation are the first report of carbazole alkaloids’ potential against antibiotic resistant clinical bacteria, MCF-7 and P388 cell lines.

  7. Biological activity of carbazole alkaloids and essential oil of Murraya koenigii against antibiotic resistant microbes and cancer cell lines. (United States)

    Nagappan, Thilahgavani; Ramasamy, Perumal; Wahid, Mohd Effendy Abdul; Segaran, Thirukanthan Chandra; Vairappan, Charles S


    A total of three carbazole alkaloids and essential oil from the leaves of Murraya koenigii (Rutaceae) were obtained and examined for their effects on the growth of five antibiotic resistant pathogenic bacteria and three tumor cell lines (MCF-7, P 388 and Hela). The structures of these carbazoles were elucidated based on spectroscopy data and compared with literature data, hence, were identified as mahanine (1), mahanimbicine (2) and mahanimbine (3). The chemical constituents of the essential oil were identified using Gas Chromatography-Mass Spectroscopy (GCMS). These compounds exhibited potent inhibition against antibiotic resistant bacteria such as Staphylococcus aureus (210P JTU), Psedomonas aeruginosa (ATCC 25619), Klebsiella pneumonia (SR1-TU), Escherchia coli (NI23 JTU) and Streptococcus pneumoniae (SR16677-PRSP) with significant minimum inhibition concentration (MIC) values (25.0-175.0 mg/mL) and minimum bacteriacidal concentrations (MBC) (100.0-500.0 mg/mL). The isolated compounds showed significant antitumor activity against MCF-7, Hela and P388 cell lines. Mahanimbine (3) and essential oil in particular showed potent antibacteria and cytotoxic effect with dose dependent trends (≤5.0 μg/mL). The findings from this investigation are the first report of carbazole alkaloids' potential against antibiotic resistant clinical bacteria, MCF-7 and P388 cell lines.

  8. Cancer stem cells revisited

    NARCIS (Netherlands)

    Batlle, Eduard; Clevers, Hans


    The cancer stem cell (CSC) concept was proposed four decades ago, and states that tumor growth, analogous to the renewal of healthy tissues, is fueled by small numbers of dedicated stem cells. It has gradually become clear that many tumors harbor CSCs in dedicated niches, and yet their

  9. Inflammation and cancer stem cells. (United States)

    Shigdar, Sarah; Li, Yong; Bhattacharya, Santanu; O'Connor, Michael; Pu, Chunwen; Lin, Jia; Wang, Tao; Xiang, Dongxi; Kong, Lingxue; Wei, Ming Q; Zhu, Yimin; Zhou, Shufeng; Duan, Wei


    Cancer stem cells are becoming recognised as being responsible for metastasis and treatment resistance. The complex cellular and molecular network that regulates cancer stem cells and the role that inflammation plays in cancer progression are slowly being elucidated. Cytokines, secreted by tumour associated immune cells, activate the necessary pathways required by cancer stem cells to facilitate cancer stem cells progressing through the epithelial-mesenchymal transition and migrating to distant sites. Once in situ, these cancer stem cells can secrete their own attractants, thus providing an environment whereby these cells can continue to propagate the tumour in a secondary niche. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  10. Human mammary microenvironment better regulates the biology of human breast cancer in humanized mouse model. (United States)

    Zheng, Ming-Jie; Wang, Jue; Xu, Lu; Zha, Xiao-Ming; Zhao, Yi; Ling, Li-Jun; Wang, Shui


    During the past decades, many efforts have been made in mimicking the clinical progress of human cancer in mouse models. Previously, we developed a human breast tissue-derived (HB) mouse model. Theoretically, it may mimic the interactions between "species-specific" mammary microenvironment of human origin and human breast cancer cells. However, detailed evidences are absent. The present study (in vivo, cellular, and molecular experiments) was designed to explore the regulatory role of human mammary microenvironment in the progress of human breast cancer cells. Subcutaneous (SUB), mammary fat pad (MFP), and HB mouse models were developed for in vivo comparisons. Then, the orthotopic tumor masses from three different mouse models were collected for primary culture. Finally, the biology of primary cultured human breast cancer cells was compared by cellular and molecular experiments. Results of in vivo mouse models indicated that human breast cancer cells grew better in human mammary microenvironment. Cellular and molecular experiments confirmed that primary cultured human breast cancer cells from HB mouse model showed a better proliferative and anti-apoptotic biology than those from SUB to MFP mouse models. Meanwhile, primary cultured human breast cancer cells from HB mouse model also obtained the migratory and invasive biology for "species-specific" tissue metastasis to human tissues. Comprehensive analyses suggest that "species-specific" mammary microenvironment of human origin better regulates the biology of human breast cancer cells in our humanized mouse model of breast cancer, which is more consistent with the clinical progress of human breast cancer.

  11. Emerging molecular approaches in stem cell biology. (United States)

    Jaishankar, Amritha; Vrana, Kent


    Stem cells are characterized by their ability to self-renew and differentiate into multiple adult cell types. Although substantial progress has been made over the last decade in understanding stem cell biology, recent technological advances in molecular and systems biology may hold the key to unraveling the mystery behind stem cell self-renewal and plasticity. The most notable of these advances is the ability to generate induced pluripotent cells from somatic cells. In this review, we discuss our current understanding of molecular similarities and differences among various stem cell types. Moreover, we survey the current state of systems biology and forecast future needs and direction in the stem cell field.

  12. Fostering synergy between cell biology and systems biology. (United States)

    Eddy, James A; Funk, Cory C; Price, Nathan D


    In the shared pursuit of elucidating detailed mechanisms of cell function, systems biology presents a natural complement to ongoing efforts in cell biology. Systems biology aims to characterize biological systems through integrated and quantitative modeling of cellular information. The process of model building and analysis provides value through synthesizing and cataloging information about cells and molecules, predicting mechanisms and identifying generalizable themes, generating hypotheses and guiding experimental design, and highlighting knowledge gaps and refining understanding. In turn, incorporating domain expertise and experimental data is crucial for building towards whole cell models. An iterative cycle of interaction between cell and systems biologists advances the goals of both fields and establishes a framework for mechanistic understanding of the genome-to-phenome relationship. Crown Copyright © 2015. Published by Elsevier Ltd. All rights reserved.

  13. Synthesis and Biological Activities of a 3'-Azido Analogue of Doxorubicin Against Drug-Resistant Cancer Cells

    Directory of Open Access Journals (Sweden)

    Fengshan Wang


    Full Text Available Doxorubicin (DOX, an anthracycline antibiotic, is one of the most active anticancer chemotherapeutic agents. The clinical use of DOX, however, is limited by the dose-dependant P-glycoprotein (P-gp-mediated resistance. Herein, a 3′-azido analogue of DOX (ADOX was prepared from daunorubicin (DNR. ADOX exhibited potent antitumor activities in drug-sensitive (MCF-7 and K562 and drug-resistant cell lines (MCF-7/DNR, K562/DOX, respectively. The drug resistance index (DRI values of ADOX were much lower than that of DOX. The cytotoxicity experiments of ADOX or DOX against K562/DOX, with or without P-gp inhibitor, indicated that ADOX circumvents resistance by abolishing the P-gp recognition. This conclusion was further supported by drug influx/efflux flow cytometry experiments, as well as by molecular docking of ADOX to P-gp. In vivo animal tests, ADOX exhibited higher activity and less toxicity than DOX. The current data warranted ADOX for additional pre-clinical evaluations for new drug development.

  14. The redox biology network in cancer pathophysiology and therapeutics

    Directory of Open Access Journals (Sweden)

    Gina Manda


    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

  15. Cell Science and Cell Biology Research at MSFC: Summary (United States)


    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.

  16. Cell and molecular biology of epidermal growth factor receptor. (United States)

    Ceresa, Brian P; Peterson, Joanne L


    The epidermal growth factor receptor (EGFR) has been one of the most intensely studied cell surface receptors due to its well-established roles in developmental biology, tissue homeostasis, and cancer biology. The EGFR has been critical for creating paradigms for numerous aspects of cell biology, such as ligand binding, signal transduction, and membrane trafficking. Despite this history of discovery, there is a continual stream of evidence that only the surface has been scratched. New ways of receptor regulation continue to be identified, each of which is a potential molecular target for manipulating EGFR signaling and the resultant changes in cell and tissue biology. This chapter is an update on EGFR-mediated signaling, and describes some recent developments in the regulation of receptor biology.

  17. ROS signalling in the biology of cancer. (United States)

    Moloney, Jennifer N; Cotter, Thomas G


    Increased reactive oxygen species (ROS) production has been detected in various cancers and has been shown to have several roles, for example, they can activate pro-tumourigenic signalling, enhance cell survival and proliferation, and drive DNA damage and genetic instability. Counterintuitively ROS can also promote anti-tumourigenic signalling, initiating oxidative stress-induced tumour cell death. Tumour cells express elevated levels of antioxidant proteins to detoxify elevated ROS levels, establish a redox balance, while maintaining pro-tumourigenic signalling and resistance to apoptosis. Tumour cells have an altered redox balance to that of their normal counterparts and this identifies ROS manipulation as a potential target for cancer therapies. This review discusses the generation and sources of ROS within tumour cells, the regulation of ROS by antioxidant defence systems, as well as the effect of elevated ROS production on their signalling targets in cancer. It also provides an insight into how pro- and anti-tumourigenic ROS signalling pathways could be manipulated in the treatment of cancer. Copyright © 2017 Elsevier Ltd. All rights reserved.

  18. [Cell surface carbohydrates are involved in various biological processes]. (United States)

    Bryne, M; Kjaerheim, A; Schreurs, O; Dabelsteen, E


    All human cells show carbohydrate structures on the surface. New knowledge about the genetic mechanisms for the synthesis of these carbohydrates and the generation of monoclonal antibodies with high specificity shows that carbohydrates are involved in various cell-cell and cell-matrix interactions. For instance, cell surface carbohydrates seem to be important in connection with fertilization, embryonic development, cell differentiation, cancer, adhesion of microorganisms and immunological processes. This new knowledge will increase our understanding of various biological phenomena, and will thus be of value for diagnosis and treatment of various diseases.

  19. Histone variants: emerging players in cancer biology (United States)

    Vardabasso, Chiara; Hasson, Dan; Ratnakumar, Kajan; Chung, Chi-Yeh; Duarte, Luis F.


    Histone variants are key players in shaping chromatin structure, and, thus, in regulating fundamental cellular processes such as chromosome segregation and gene expression. Emerging evidence points towards a role for histone variants in contributing to tumor progression, and, recently, the first cancer-associated mutation in a histone variant-encoding gene was reported. In addition, genetic alterations of the histone chaperones that specifically regulate chromatin incorporation of histone variants are rapidly being uncovered in numerous cancers. Collectively, these findings implicate histone variants as potential drivers of cancer initiation and/or progression, and, therefore, targeting histone deposition or the chromatin remodeling machinery may be of therapeutic value. Here, we review the mammalian histone variants of the H2A and H3 families in their respective cellular functions, and their involvement in tumor biology. PMID:23652611

  20. Biological therapeutics of Pongamia pinnata coated zinc oxide nanoparticles against clinically important pathogenic bacteria, fungi and MCF-7 breast cancer cells. (United States)

    Malaikozhundan, Balasubramanian; Vaseeharan, Baskaralingam; Vijayakumar, Sekar; Pandiselvi, Karuppiah; Kalanjiam, Mohamed Ali Rajamohamed; Murugan, Kadarkarai; Benelli, Giovanni


    The overuse of antimicrobics and drugs has led to the development of resistance in a number of pathogens and parasites, which leads to great concerns for human health and the environment. Furthermore, breast cancer is the second most common cause of cancer death in women. MCF-7 is a widely used epithelial cancer cell line, derived from breast adenocarcinoma for in vitro breast cancer studies, since the cell line has retained several ideal characteristics particular to the mammary epithelium. In this scenario, the development of novel and eco-friendly drugs are of timely importance. Green synthesis of nanoparticles is cost effective, environmental friendly and does not involve the use of toxic chemicals or elevate energy inputs. This research focused on the anticancer activity of Pongamia pinnata seed extract-fabricated zinc oxide nanoparticles (Pp-ZnO NPs) on human MCF-7 breast cancer cells, antibiofilm activity against bacteria and fungi was also investigated. Nanoparticles were characterized by UV-Vis spectroscopy, X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FTIR), Scanning electron microscopy (SEM) and Energy dispersive X-ray spectroscopy (EDX). Pp-ZnO NPs effectively inhibited the growth of Gram positive Bacillus licheniformis (zone of inhibition: 17.3 mm) at 25 μg ml-1 followed by Gram negative Pseudomonas aeruginosa (14.2 mm) and Vibrio parahaemolyticus (12.2 mm). Pp-ZnO NPs also effectively inhibited the biofilm formation of C. albicans at 50 μg ml-1. Cytotoxicity studies revealed that a single treatment with Pp-ZnO NPs significantly reduced the cell viability of breast cancer MCF-7 cells at doses higher than 50 μg ml-1. Morphological changes in the Pp-ZnO NPs treated MCF-7 breast cancer cells were observed using phase contrast microscopy. This study concludes that the green synthesized Pp-ZnO NPs may be used as an effective antimicrobial and antibreast cancer agents. Copyright © 2017 Elsevier Ltd. All rights reserved.

  1. Evolutionary cell biology: two origins, one objective. (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


    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.

  2. Tumor associated macrophage × cancer cell hybrids may acquire cancer stem cell properties in breast cancer.

    Directory of Open Access Journals (Sweden)

    Jingxian Ding

    Full Text Available Breast cancer is one of the most frequently diagnosed cancers among women, and metastasis makes it lethal. Tumor-associated macrophages (TAMs that acquire an alternatively activated macrophage (M2 phenotype may promote metastasis. However, the underlying mechanisms are still elusive. Here, we examined how TAMs interact with breast cancer cells to promote metastasis. Immunohistochemistry was used to examine the expression of the M2-specific antigen CD163 in paraffin-embedded mammary carcinoma blocks to explore fusion events in breast cancer patients. U937 cells were used as a substitute for human monocytes, and these cells differentiated into M2 macrophages following phorbol 12-myristate 13-acetate (PMA and M-CSF stimulation. M2 macrophages and the breast cancer cell lines MCF-7 and MDA-MB-231 fused in the presence of 50% polyethylene glycol. Hybrids were isolated by fluorescence-activated cell sorting, and the relevant cell biological properties were compared with their parental counterparts. Breast cancer stem cell (BCSC-related markers were quantified by immunofluorescence staining, RT-PCR, quantitative RT-PCR and/or western blotting. The tumor-initiating and metastatic capacities of the hybrids and their parental counterparts were assessed in NOD/SCID mice. We found that the CD163 expression rate in breast cancer tissues varied significantly and correlated with estrogen receptor status (p0.05. Characterization of the fusion hybrids revealed a more aggressive phenotype, including increased migration, invasion and tumorigenicity, but reduced proliferative ability, compared with the parental lines. The hybrids also gained a CD44(+CD24(-/low phenotype and over-expressed epithelial-mesenchymal transition-associated genes. These results indicate that TAMs may promote breast cancer metastasis through cell fusion, and the hybrids may gain a BCSC phenotype.

  3. Systems Biology and Stem Cell Pluripotency

    DEFF Research Database (Denmark)

    Mashayekhi, Kaveh; Hall, Vanessa Jane; Freude, Kristine


    Recent breakthroughs in stem cell biology have accelerated research in the area of regenerative medicine. Over the past years, it has become possible to derive patient-specific stem cells which can be used to generate different cell populations for potential cell therapy. Systems biological...... modeling of stem cell pluripotency and differentiation have largely been based on prior knowledge of signaling pathways, gene regulatory networks, and epigenetic factors. However, there is a great need to extend the complexity of the modeling and to integrate different types of data, which would further...... improve systems biology and its uses in the field. In this chapter, we first give a general background on stem cell biology and regenerative medicine. Stem cell potency is introduced together with the hierarchy of stem cells ranging from pluripotent embryonic stem cells (ESCs) and induced pluripotent stem...

  4. Protease-activated receptors – biology and role in cancer

    Directory of Open Access Journals (Sweden)

    Dominika Hempel


    Full Text Available The fact that blood coagulation disorders may accompany malignant disease is well established. However, many studies have shown that components of the haemostatic system may also elicit signaling leading to cancer developement and progression. The potential mechanism by which coagulation factors play a role in cancer invasion is not completely understood, but one hypothesis is that protease-activated receptors (PARs play a prominent role. PARs are transmembrane G-protein-coupled receptors (GPCRs that are activated by a unique proteolytic mechanism. They have important functions in haemostasis and inflammation but may also be implicated in cancer cell progression. Thrombin, tissue factor (TF and matrix metalloproteinases (MMPs are the main activators of these receptors. The mechanism of persistent activation of PARs was also described in cancer cells. Here, we discuss the physiological and pathological role of PARs with a particular focus on PARs’ contribution to cancer biology. We also present therapeutic options tailored specifically to inhibition of PAR-induced signalling in cancer patients.

  5. Stem Cells and Cancer; Celulas madre y cancer

    Energy Technology Data Exchange (ETDEWEB)

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


    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)

  6. Dissecting social cell biology and tumors using Drosophila genetics. (United States)

    Pastor-Pareja, José Carlos; Xu, Tian


    Cancer was seen for a long time as a strictly cell-autonomous process in which oncogenes and tumor-suppressor mutations drive clonal cell expansions. Research in the past decade, however, paints a more integrative picture of communication and interplay between neighboring cells in tissues. It is increasingly clear as well that tumors, far from being homogenous lumps of cells, consist of different cell types that function together as complex tissue-level communities. The repertoire of interactive cell behaviors and the quantity of cellular players involved call for a social cell biology that investigates these interactions. Research into this social cell biology is critical for understanding development of normal and tumoral tissues. Such complex social cell biology interactions can be parsed in Drosophila. Techniques in Drosophila for analysis of gene function and clonal behavior allow us to generate tumors and dissect their complex interactive biology with cellular resolution. Here, we review recent Drosophila research aimed at understanding tissue-level biology and social cell interactions in tumors, highlighting the principles these studies reveal.

  7. 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.

  8. Squamous cell skin cancer (United States)

    ... squamous cell cancer include: Having light-colored skin, blue or green eyes, or blond or red hair Long-term, daily sun exposure (such as in people who work outside) Many severe sunburns early in life Older age Having had many x-rays Chemical exposure A weakened immune system, especially in ...

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

  10. Invasive cancer cells and metastasis (United States)

    Mierke, Claudia Tanja


    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

  11. Microfluidic tools for cell biological research


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


    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.

  12. Natural Killer T Cells: An Ecological Evolutionary Developmental Biology Perspective

    Directory of Open Access Journals (Sweden)

    Amrendra Kumar


    Full Text Available Type I natural killer T (NKT cells are innate-like T lymphocytes that recognize glycolipid antigens presented by the MHC class I-like protein CD1d. Agonistic activation of NKT cells leads to rapid pro-inflammatory and immune modulatory cytokine and chemokine responses. This property of NKT cells, in conjunction with their interactions with antigen-presenting cells, controls downstream innate and adaptive immune responses against cancers and infectious diseases, as well as in several inflammatory disorders. NKT cell properties are acquired during development in the thymus and by interactions with the host microbial consortium in the gut, the nature of which can be influenced by NKT cells. This latter property, together with the role of the host microbiota in cancer therapy, necessitates a new perspective. Hence, this review provides an initial approach to understanding NKT cells from an ecological evolutionary developmental biology (eco-evo-devo perspective.

  13. Concise Review: Stem Cell Population Biology: Insights from Hematopoiesis. (United States)

    MacLean, Adam L; Lo Celso, Cristina; Stumpf, Michael P H


    Stem cells are fundamental to human life and offer great therapeutic potential, yet their biology remains incompletely-or in cases even poorly-understood. The field of stem cell biology has grown substantially in recent years due to a combination of experimental and theoretical contributions: the experimental branch of this work provides data in an ever-increasing number of dimensions, while the theoretical branch seeks to determine suitable models of the fundamental stem cell processes that these data describe. The application of population dynamics to biology is amongst the oldest applications of mathematics to biology, and the population dynamics perspective continues to offer much today. Here we describe the impact that such a perspective has made in the field of stem cell biology. Using hematopoietic stem cells as our model system, we discuss the approaches that have been used to study their key properties, such as capacity for self-renewal, differentiation, and cell fate lineage choice. We will also discuss the relevance of population dynamics in models of stem cells and cancer, where competition naturally emerges as an influential factor on the temporal evolution of cell populations. Stem Cells 2017;35:80-88. © 2016 AlphaMed Press.

  14. Alcohol and Cancer Stem Cells


    Mei Xu; Jia Luo


    Heavy alcohol consumption has been associated with increased risk of several cancers, including cancer of the colon, rectum, female breast, oral cavity, pharynx, larynx, liver, and esophagus. It appears that alcohol exposure not only promotes carcinogenesis but also enhances the progression and aggressiveness of existing cancers. The molecular mechanisms underlying alcohol tumor promotion, however, remain unclear. Cancer stem cells (CSC), a subpopulation of cancer cells with self-renewal and ...

  15. Mammalian synthetic biology for studying the cell


    Mathur, Melina; Xiang, Joy S.; Smolke, Christina D.


    Synthetic biology is advancing the design of genetic devices that enable the study of cellular and molecular biology in mammalian cells. These genetic devices use diverse regulatory mechanisms to both examine cellular processes and achieve precise and dynamic control of cellular phenotype. Synthetic biology tools provide novel functionality to complement the examination of natural cell systems, including engineered molecules with specific activities and model systems that mimic complex regula...

  16. Undergraduate Students' Mental Model of Cell Biology


    S. Saptono; W. Isnaeni; S. Sukaesih


    A descriptive study of future teacher students' mental models of essential concepts in Cell Biology was carried out through explanatory mixed-methods. Some students (n=40) of Biology Education Universitas Negeri Semarang were involved as the research subject. We used a diagnostic test, structured interview guides, and field notes to describe students' mental model. In the early stage, we prepare a diagnostic test performed essential concepts of Cell Biology. Secondly, we define students' ment...

  17. Biological evaluation of a cytotoxic 2-substituted benzimidazole copper(II) complex: DNA damage, antiproliferation and apoptotic induction activity in human cervical cancer cells. (United States)

    Qiao, Xin; Ma, Zhong-Ying; Shao, Jia; Bao, Wei-Guo; Xu, Jing-Yuan; Qiang, Zhao-Yan; Lou, Jian-Shi


    Exploring novel chemotherapeutic agents is a great challenge in cancer medicine. To that end, 2-substituted benzimidazole copper(II) complex, [Cu(BMA)Cl2]·(CH3OH) (1) [BMA = N,N'-bis(benzimidazol-2-yl-methyl)amine], was synthesized and its cytotoxicity was characterized. The interaction between complex 1 and calf thymus DNA was detected by spectroscopy methods. The binding constant (K b = 1.24 × 10(4 )M(-1)) and the apparent binding constant (K app = 6.67 × 10(6 )M(-1)) of 1 indicated its moderate DNA affinity. Complex 1 induced single strand breaks of pUC19 plasmid DNA in the presence of H2O2 through an oxidative pathway. Cytotoxicity studies proved that complex 1 could inhibit the proliferation of human cervical carcinoma cell line HeLa in both time- and dose-dependent manners. The results of nuclei staining by Hoechst 33342 and alkaline single-cell gel electrophoresis proved that complex 1 caused cellular DNA damage in HeLa cells. Furthermore, treatment of HeLa cells with 1 resulted in S-phase arrest, loss of mitochondrial potential, and up-regulation of caspase-3 and -9 in HeLa cells, suggesting that complex 1 was capable of inducing apoptosis in cancer cells through the intrinsic mitochondrial pathway.

  18. [Thyroid cancers: from epidemiology to molecular biology]. (United States)

    Lalmi, F; Sadoul, J-L; Rohmer, V


    Experts increasingly recognize the hypothesis of "over-diagnosis" as the main factor of the raising incidence of thyroid cancers (TC). The detection of multiple microtumors, mainly of a papillary type, at a sub-clinical stage, with the use of sensitive detection methods supports this hypothesis. However, the intensive management and monitoring of these cancers failed to reduce mortality. Environmental and other risk factors cannot provide a sufficient explanation, as previously thought. In this context, the use of improved tools is needed, and the most promising perspective lies in molecular biology applied to thyroid cancer for diagnosis, evaluation of prognosis and treatment. The next generation sequencing (NGS) has demonstrated its diagnostic performances in recent clinical trials. Its interest in cases with indeterminate cytology is demonstrated and should help better targeting surgical indications. Its promising prognostic and therapeutic applications must be confirmed by additional studies. The integration of NGS in current practice should have a real medical, economic and scientific impact. Indeed, the exponential increase in our knowledge of molecular mechanisms of thyroid tumorigenesis strengthens the will to "reclassify" these cancers into molecular rather than histological subtypes, in order to offer patients more specific and targeted treatment. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

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

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    Matsuyama, Tomohiko, E-mail: [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)


    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.

  20. 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.

  1. Colon cancer stem cells dictate tumor growth and resist cell death by production of interleukin-4

    NARCIS (Netherlands)

    Todaro, Matilde; Alea, Mileidys Perez; Di Stefano, Anna B.; Cammareri, Patrizia; Vermeulen, Louis; Iovino, Flora; Tripodo, Claudio; Russo, Antonio; Gulotta, Gaspare; Medema, Jan Paul; Stassi, Giorgio


    A novel paradigm in tumor biology suggests that cancer growth is driven by stem-like cells within a tumor. Here, we describe the identification and characterization of such cells from colon carcinomas using the stem cell marker CD133 that accounts around 2% of the cells in human colon cancer. The

  2. Micro and nano-platforms for biological cell analysis

    DEFF Research Database (Denmark)

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


    In this paper some technological platforms developed for biological cell analysis will be presented and compared to existing systems. In brief, we present a novel micro cell culture chamber based on diffusion feeding of cells, into which cells can be introduced and extracted after culturing using...... from the cells, while passive modifications involve the presence of a peptide nanotube based scaffold for the cell culturing that mimics the in vivo environment. Two applications involving fluorescent in situ hybridization (FISH) analysis and cancer cell sorting are presented, as examples of further...... analysis that can be done after cell culturing. A platform able to automate the entire process from cell culturing to cell analysis by means of simple plug and play of various self-contained, individually fabricated modules is finally described....

  3. The Changing Landscape of Breast Cancer: How Biology Drives Therapy

    Directory of Open Access Journals (Sweden)

    Sarah Friend


    Full Text Available Breast cancer is the most prevalent life-threatening cancer in women. Optimizing therapy to increase cure rates in early stage disease, and improving life expectancy and palliation for advanced stages, are goals driving major areas of research. The armamentarium of targeted treatments for breast cancer is ever expanding as understanding of breast cancer biology deepens. A revolution in our treatment was heralded a decade ago by the introduction of trastuzumab for human epidermal receptor-2 positive (HER2+ disease resulting in remarkable reductions in recurrence and improvements in overall survival (OS. Advances continue to be made in other breast cancer subtypes targeting key activating pathways for therapeutic development. However, for these other targeted agents, improvement in OS has been elusive. This article focuses on the development of targeted therapy in breast cancer focusing primarily on the last 5 years, to illustrate that as we understand the complex pathways allowing the dysregulated cell to become malignant, it also propels us closer towards the promise of precision and personalized medicine.

  4. Lipid Rafts in Mast Cell Biology

    Directory of Open Access Journals (Sweden)

    Adriana Maria Mariano Silveira e Souza


    Full Text Available Mast cells have long been recognized to have a direct and critical role in allergic and inflammatory reactions. In allergic diseases, these cells exert both local and systemic responses, including allergic rhinitis and anaphylaxis. Mast cell mediators are also related to many chronic inflammatory conditions. Besides the roles in pathological conditions, the biological functions of mast cells include roles in innate immunity, involvement in host defense mechanisms against parasites, immunomodulation of the immune system, tissue repair, and angiogenesis. Despite their growing significance in physiological and pathological conditions, much still remains to be learned about mast cell biology. This paper presents evidence that lipid rafts or raft components modulate many of the biological processes in mast cells, such as degranulation and endocytosis, play a role in mast cell development and recruitment, and contribute to the overall preservation of mast cell structure and organization.

  5. Cancer stem cells in head and neck cancer

    Directory of Open Access Journals (Sweden)

    Trapasso S


    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. Modeling cell-in-cell structure into its biological significance. (United States)

    He, M-f; Wang, S; Wang, Y; Wang, X-n


    Although cell-in-cell structure was noted 100 years ago, the molecular mechanisms of 'entering' and the destination of cell-in-cell remain largely unclear. It takes place among the same type of cells (homotypic cell-in-cell) or different types of cells (heterotypic cell-in-cell). Cell-in-cell formation affects both effector cells and their host cells in multiple aspects, while cell-in-cell death is under more intensive investigation. Given that cell-in-cell has an important role in maintaining homeostasis, aberrant cell-in-cell process contributes to the etiopathology in humans. Indeed, cell-in-cell is observed in many pathological processes of human diseases. In this review, we intend to discuss the biological models of cell-in-cell structures under physiological and pathological status.

  7. Mammalian synthetic biology for studying the cell. (United States)

    Mathur, Melina; Xiang, Joy S; Smolke, Christina D


    Synthetic biology is advancing the design of genetic devices that enable the study of cellular and molecular biology in mammalian cells. These genetic devices use diverse regulatory mechanisms to both examine cellular processes and achieve precise and dynamic control of cellular phenotype. Synthetic biology tools provide novel functionality to complement the examination of natural cell systems, including engineered molecules with specific activities and model systems that mimic complex regulatory processes. Continued development of quantitative standards and computational tools will expand capacities to probe cellular mechanisms with genetic devices to achieve a more comprehensive understanding of the cell. In this study, we review synthetic biology tools that are being applied to effectively investigate diverse cellular processes, regulatory networks, and multicellular interactions. We also discuss current challenges and future developments in the field that may transform the types of investigation possible in cell biology. © 2017 Mathur et al.

  8. Classification and biology of tumour associated stromal cells. (United States)

    Raffaghello, Lizzia; Dazzi, Francesco


    Stroma is a fundamental component of the tumour microenvironment whereby it supports malignant cell growth and spreading. It consists of different entities including cells of the immune system, vascular structures and fibroblasts. Much attention has recently been paid to fibroblasts since there is compelling evidence that they orchestrate the recruitment of and educate other cells to promote cancer growth. This review proposes to discuss in detail the nomenclature, origin, and biological functions of the different stromal cells residing in tumours. Copyright © 2015 European Federation of Immunological Societies. Published by Elsevier B.V. All rights reserved.

  9. Tumor biology and cancer therapy – an evolving relationship

    Directory of Open Access Journals (Sweden)

    Lother Ulrike


    Full Text Available Abstract The aim of palliative chemotherapy is to increase survival whilst maintaining maximum quality of life for the individual concerned. Although we are still continuing to explore the optimum use of traditional chemotherapy agents, the introduction of targeted therapies has significantly broadened the therapeutic options. Interestingly, the results from current trials put the underlying biological concept often into a new, less favorable perspective. Recent data suggested that altered pathways underlie cancer, and not just altered genes. Thus, an effective therapeutic agent will sometimes have to target downstream parts of a signaling pathway or physiological effects rather than individual genes. In addition, over the past few years increasing evidence has suggested that solid tumors represent a very heterogeneous group of cells with different susceptibility to cancer therapy. Thus, since therapeutic concepts and pathophysiological understanding are continuously evolving a combination of current concepts in tumor therapy and tumor biology is needed. This review aims to present current problems of cancer therapy by highlighting exemplary results from recent clinical trials with colorectal and pancreatic cancer patients and to discuss the current understanding of the underlying reasons.

  10. Blood type study sheds light on biology of pancreatic cancer

    National Research Council Canada - National Science Library


    Offering a novel clue about the basic biology of pancreatic cancer, researchers at Dana-Farber Cancer Institute have confirmed a decades-old discovery of a link between blood type and the risk of developing the disease...

  11. Studying cell biology in the skin. (United States)

    Morrow, Angel; Lechler, Terry


    Advances in cell biology have often been driven by studies in diverse organisms and cell types. Although there are technical reasons for why different cell types are used, there are also important physiological reasons. For example, ultrastructural studies of vesicle transport were aided by the use of professional secretory cell types. The use of tissues/primary cells has the advantage not only of using cells that are adapted to the use of certain cell biological machinery, but also of highlighting the physiological roles of this machinery. Here we discuss advantages of the skin as a model system. We discuss both advances in cell biology that used the skin as a driving force and future prospects for use of the skin to understand basic cell biology. A unique combination of characteristics and tools makes the skin a useful in vivo model system for many cell biologists. © 2015 Morrow and Lechler. This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (

  12. Cancer Stem Cells and Epithelial Ovarian Cancer

    Directory of Open Access Journals (Sweden)

    Sheetal Dyall


    Full Text Available The cancer stem cell hypothesis is becoming more widely accepted as a model for carcinogenesis. Tumours are heterogeneous both at the molecular and cellular level, containing a small population of cells that possess highly tumourigenic “stem-cell” properties. Cancer stem cells (CSCs, or tumour-initiating cells, have the ability to self-renew, generate xenografts reminiscent of the primary tumour that they were derived from, and are chemoresistant. The characterisation of the CSC population within a tumour that drives its growth could provide novel target therapeutics against these cells specifically, eradicating the cancer completely. There have been several reports describing the isolation of putative cancer stem cell populations in several cancers; however, no defined set of markers has been identified that conclusively characterises “stem-like” cancer cells. This paper highlights the current experimental approaches that have been used in the field and discusses their limitations, with specific emphasis on the identification and characterisation of the CSC population in epithelial ovarian cancer.

  13. Male breast cancer: risk factors, biology, diagnosis, treatment, and survivorship

    National Research Council Canada - National Science Library

    Ruddy, K J; Winer, E P


    ...'. Relevant published data regarding risk factors, biological characteristics, presentation and prognosis, appropriate evaluation and treatment, and survivorship issues in male breast cancer patients are presented...

  14. Synthesis, Characterization, and Biological Evaluation of Anti-HER2 Indocyanine Green-Encapsulated PEG-Coated PLGA Nanoparticles for Targeted Phototherapy of Breast Cancer Cells.

    Directory of Open Access Journals (Sweden)

    Yu-Hsiang Lee

    Full Text Available Human epidermal growth factor receptor 2 (HER2-overexpressed breast cancer is known to be more aggressive and resistant to medicinal treatment and therefore to whom an alternative therapeutics is needed. Indocyanine green (ICG has been widely exploited in breast cancer phototherapy. However, drawbacks of accelerated degradation and short half-life (2-4 min in blood seriously hamper its use in the clinic. To overcome these challenges, an anti-HER2 ICG-encapsulated polyethylene glycol-coated poly(lactic-co-glycolic acid nanoparticles (HIPPNPs were developed in this study. Through the analyses of degradation rate coefficients of ICG with and without polymeric encapsulation, the photostability of HIPPNP-entrapped ICG significantly enhanced 4 folds (P 90% of the cells were eradicated while the dose of HIPPNPs was increased to 25 μM ICG equivalent. In summary, the developed HIPPNPs are anticipated as a feasible tool for use in phototherapy of breast cancer cells with HER2 expression.

  15. Natural killer cell biology: an update and future directions. (United States)

    Campbell, Kerry S; Hasegawa, Jun


    Natural killer (NK) cells constitute a minor subset of normal lymphocytes that initiate innate immune responses toward tumor and virus-infected cells. They can mediate spontaneous cytotoxicity toward these abnormal cells and rapidly secrete numerous cytokines and chemokines to promote subsequent adaptive immune responses. Significant progress has been made in the past 2 decades to improve our understanding of NK cell biology. Here we review recent discoveries, including a better comprehension of the "education" of NK cells to achieve functional competence during their maturation and the discovery of "memory" responses by NK cells, suggesting that they might also contribute to adaptive immunity. The improved understanding of NK cell biology has forged greater awareness that these cells play integral early roles in immune responses. In addition, several promising clinical therapies have been used to exploit NK cell functions in treating patients with cancer. As our molecular understanding improves, these and future immunotherapies should continue to provide promising strategies to exploit the unique functions of NK cells to treat cancer, infections, and other pathologic conditions. Copyright © 2013 American Academy of Allergy, Asthma & Immunology. Published by Mosby, Inc. All rights reserved.

  16. Biological cell classification by multiangle light scattering (United States)

    Salzman, G.C.; Crowell, J.M.; Mullaney, P.F.


    The specification is directed to an apparatus and method for detecting light scattering from a biological cell. Light, preferably from a coherent source of radiation, intercepts an individual biological cell in a stream of cells passing through the beam. Light scattered from the cell is detected at a selected number of angles between 0 and 90/sup 0/ to the longitudinal axis of the beam with a circular array of light responsive elements which produce signals representative of the intensity of light incident thereon. Signals from the elements are processed to determine the light-scattering pattern of the cell and therefrom its identity.

  17. Cancer treatments transform residual cancer cell phenotype

    Directory of Open Access Journals (Sweden)

    Harless William W


    Full Text Available Abstract Background Physiologic wound repair and tissue regeneration are associated with distinct cellular behaviors triggered by tissue damage. Normally quiescent stem cells proliferate to regenerate damaged tissue, while relatively immobile epithelial cells can transform into a motile, tissue invasive phenotype through a partial epithelial-mesenchymal transition. These distinct cellular behaviors may have particular relevance to how cancer cells can be predicted to behave after treatments damaging a tumor. Presentation of the hypothesis Surgery, chemotherapy, and radiation therapy trigger highly conserved wound healing pathways that: (1 facilitate the phenotypic transformation of surviving cancer cells into a highly mobile, metastatic phenotype through an EMT or epithelial-mesenchymal transition and (2 induce residual cancer stem cell proliferation. Testing the hypothesis Tissue damage caused by cancer treatments will trigger the release of distinct cytokines with established roles in physiologic wound healing, EMT induction, and stem cell activation. They will be released rapidly after treatment and detectable in the patient's blood. Careful histologic evaluation of cancerous tissue before and after treatment will reveal cellular changes suggestive of EMT induction (down regulation of cytokeratin expression and cancer stem cell enrichment (stem cell markers upregulated. Implications of the hypothesis Cancer cells surviving treatment will be more capable of metastasis and resistant to conventional therapies than the pre-treatment population of cancer cells. These changes will develop rapidly after treatment and, in distinct contrast to selection pressures fostering such changes, be triggered by highly conserved wound repair signals released after tissue damage. This pattern of tissue (tumor repair may be amenable to treatment intervention at the time it is upregulated.

  18. Cancer stem cells and personalized cancer nanomedicine. (United States)

    Gener, Petra; Rafael, Diana Fernandes de Sousa; Fernández, Yolanda; Ortega, Joan Sayós; Arango, Diego; Abasolo, Ibane; Videira, Mafalda; Schwartz, Simo


    Despite the progress in cancer treatment over the past years advanced cancer is still an incurable disease. Special attention is pointed toward cancer stem cell (CSC)-targeted therapies, because this minor cell population is responsible for the treatment resistance, metastatic growth and tumor recurrence. The recently described CSC dynamic phenotype and interconversion model of cancer growth hamper even more the possible success of current cancer treatments in advanced cancer stages. Accordingly, CSCs can be generated through dedifferentiation processes from non-CSCs, in particular, when CSC populations are depleted after treatment. In this context, the use of targeted CSC nanomedicines should be considered as a promising tool to increase CSC sensitivity and efficacy of specific anti-CSC therapies.

  19. Phenotype heterogeneity in cancer cell populations

    Energy Technology Data Exchange (ETDEWEB)

    Almeida, Luis [CNRS UMR 7598, LJLL, & INRIA MAMBA team, Sorbonne Universités, UPMC Univ Paris 06, Boîte courrier 187, 4 Pl. Jussieu, 75252 Paris cedex 05, France, (France); Chisholm, Rebecca [School of Biotechnology and Biomolecular Sciences, University of New South Wales, Sydney, Australia, (Australia); Clairambault, Jean [INRIA MAMBA team & LJLL, UMR 7598, Sorbonne Universités, UPMC Univ Paris 06, Boîte courrier 187, 4 Pl. Jussieu, 75252 Paris cedex 05, France,, Corresponding author (France); Escargueil, Alexandre [INSERM “Cancer Biology and Therapeutics”, Sorbonne Universités, UPMC Univ Paris 06, UMR-S 938, CDR St Antoine, Hôpital St Antoine, 184 Fbg. St Antoine, 75571 Paris cedex 12, France, (France); Lorenzi, Tommaso [CMLA, ENS Cachan, 61, Av. du Président Wilson, 94230 Cachan cedex & INRIA MAMBA team, & LJLL, UMR 7598, UPMC Univ Paris 06, Boîte courrier 187, 4 Pl. Jussieu, 75252 Paris cedex 05, France, (France); Lorz, Alexander [Sorbonne Universités, UPMC Univ Paris 06, LJLL, UMR 7598 & INRIA Boîte courrier 187, 4 Pl. Jussieu, 75252 Paris cedex 05, France, (France); Trélat, Emmanuel [Institut Universitaire de France, Sorbonne Universités, UPMC Univ Paris 06, LJLL, UMR 7598, Boîte courrier 187, UPMC Univ Paris 06, 4 Pl. Jussieu, 75252 Paris cedex 05, France, (France)


    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

  20. A chemist building paths to cell biology. (United States)

    Weibel, Douglas B


    Galileo is reported to have stated, "Measure what is measurable and make measurable what is not so." My group's trajectory in cell biology has closely followed this philosophy, although it took some searching to find this path.

  1. Biological activities of fusarochromanone: a potent anti-cancer agent. (United States)

    Mahdavian, Elahe; Palyok, Phillip; Adelmund, Steven; Williams-Hart, Tara; Furmanski, Brian D; Kim, Yoon-Jee; Gu, Ying; Barzegar, Mansoureh; Wu, Yang; Bhinge, Kaustubh N; Kolluru, Gopi K; Quick, Quincy; Liu, Yong-Yu; Kevil, Christopher G; Salvatore, Brian A; Huang, Shile; Clifford, John L


    Fusarochromanone (FC101) is a small molecule fungal metabolite with a host of interesting biological functions, including very potent anti-angiogenic and direct anti-cancer activity. Herein, we report that FC101 exhibits very potent in-vitro growth inhibitory effects (IC50 ranging from 10nM-2.5 μM) against HaCat (pre-malignant skin), P9-WT (malignant skin), MCF-7 (low malignant breast), MDA-231 (malignant breast), SV-HUC (premalignant bladder), UM-UC14 (malignant bladder), and PC3 (malignant prostate) in a time-course and dose-dependent manner, with the UM-UC14 cells being the most sensitive. FC101 induces apoptosis and an increase in proportion of cells in the sub-G1 phase in both HaCat and P9-WT cell lines as evidenced by cell cycle profile analysis. In a mouse xenograft SCC tumor model, FC101 was well tolerated, non-toxic, and achieved a 30% reduction in tumor size at a dose of 8 mg/kg/day. FC101 is also a potent anti-angiogenenic agent. At nanomolar doses, FC101 inhibits the vascular endothelial growth factor-A (VEGF-A)-mediated proliferation of endothelial cells. Our data presented here indicates that FC101 is an excellent lead candidate for a small molecule anti-cancer agent that simultaneously affects angiogenesis signaling, cancer signal transduction, and apoptosis. Further understanding of the underlying FC101's molecular mechanism may lead to the design of novel targeted and selective therapeutics, both of which are pursued targets in cancer drug discovery.

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

    DEFF Research Database (Denmark)

    Owens, T; Zeine, R


    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...

  3. Biology of Metastatic Renal Cell Carcinoma

    Directory of Open Access Journals (Sweden)

    Michele Milella, Alessandra Felici


    Full Text Available In the past ten years we have made exceptional progresses in the understanding of RCC biology, particularly by recognizing the crucial pathogenetic role of activation of the HIF/VEGF and mTOR pathways. This has resulted in the successful clinical development of anti-angiogenic and mTOR-targeted drugs, which have profoundly impacted on the natural history of the disease and have improved the duration and quality of RCC patient lives. However, further improvements are still greatly needed: 1 even in patients who obtain striking clinical responses early in the course of treatment, disease will ultimately escape control and progress to a treatment-resistant state, leading to therapeutic failure; 2 prolonged disease control usually requires 'continuous' treatment, even across different treatment lines, making the impact of chronic, low-grade, toxicities on quality of life greater and precluding, for most patients, the possibility of experiencing 'drug-free holidays'; 3 although we have successfully identified classes of drugs (or molecular mechanisms of action that are effective in a substantial proportion of patients, we still fall short of molecular predictive factors that identify individual patients who will (or will not benefit from a specific intervention and still proceed on a trial-and-error basis, far from a truly 'personalized' therapeutic approach; 4 finally (and perhaps most importantly, even in the best case scenario, currently available treatments inevitably fail to definitively 'cure' metastatic RCC patients. In this review we briefly summarize recent developments in the understanding of the molecular pathogenesis of RCC, the development of resistance/escape mechanisms, the rationale for sequencing agents with different mechanisms of action, and the importance of host-related factors. Unraveling the complex mechanisms by which RCC shapes host microenvironment and immune response and therapeutic treatments, in turn, shape both cancer

  4. Recent advances in hematopoietic stem cell biology

    DEFF Research Database (Denmark)

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


    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...... 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...

  5. 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


    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.

  6. Teaching Cell Biology in Primary Schools

    Directory of Open Access Journals (Sweden)

    Francele de Abreu Carlan


    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.

  7. Synthesis and biological evaluation of anti-cancer agents that selectively inhibit Her2 over-expressed breast cancer cell growth via down-regulation of Her2 protein. (United States)

    Zhao, Anran; Zheng, Qiaoyun; Orahoske, Cody M; Idippily, Nethrie D; Ashcraft, Morgan M; Quamine, Aicha; Su, Bin


    Compound JCC76 selectively inhibited the proliferation of human epidermal growth factor 2 (Her2) over-expressed breast cancer cells. In the current study, a ligand based structural optimization was performed to generate new analogs, and we identified derivatives 16 and 17 that showed improved activity and selectivity against Her2 positive breast cancer cells. A structure activity relationship (SAR) was summarized. Compounds 16 and 17 were also examined by western blot assay to check their effect on Her2 protein. The results reveal that the compounds could decrease the Her2 protein, which explains their selectivity to Her2 over-expressed breast cancer cells. Furthermore, the compounds inhibited the chaperone activity of small chaperone protein that could stabilize Her2 protein. Published by Elsevier Ltd.

  8. Bioengineering thermodynamics of biological cells. (United States)

    Lucia, Umberto


    Cells are open complex thermodynamic systems. They can be also regarded as complex engines that execute a series of chemical reactions. Energy transformations, thermo-electro-chemical processes and transports phenomena can occur across the cells membranes. Moreover, cells can also actively modify their behaviours in relation to changes in their environment. Different thermo-electro-biochemical behaviours occur between health and disease states. But, all the living systems waste heat, which is no more than the result of their internal irreversibility. This heat is dissipated into the environment. But, this wasted heat represent also a sort of information, which outflows from the cell toward its environment, completely accessible to any observer. The analysis of irreversibility related to this wasted heat can represent a new approach to study the behaviour of the cells themselves and to control their behaviours. So, this approach allows us to consider the living systems as black boxes and analyze only the inflows and outflows and their changes in relation to the modification of the environment. Therefore, information on the systems can be obtained by analyzing the changes in the cell heat wasted in relation to external perturbations. The bioengineering thermodynamics bases are summarized and used to analyse possible controls of the calls behaviours based on the control of the ions fluxes across the cells membranes.

  9. Cancer stem cells, cancer cell plasticity and radiation therapy. (United States)

    Vlashi, Erina; Pajonk, Frank


    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 eliminated while the survival of differentiated progeny is less critical. In this review we discuss recent reports challenging the idea of a unidirectional differentiation of cancer cells. These reports provide evidence supporting the idea that non-stem cancer cells exhibit a remarkable degree of plasticity that allows them to re-acquire cancer stem cell traits, especially in the context of radiation therapy. We summarize conditions under which differentiation is reversed and discuss the current knowledge of the underlying mechanisms. Copyright © 2014 Elsevier Ltd. All rights reserved.

  10. Demonstration and biological significance of a gastrin‐P21‐activated kinase 1 feedback loop in colorectal cancer cells (United States)

    Huynh, Nhi; Liu, Kevin H.; Yim, Mildred; Shulkes, Arthur; Baldwin, Graham S.; He, Hong


    Abstract Gastrins, including amidated gastrin17 and glycine‐extended gastrin17, are important growth factors in colorectal cancer (CRC). The p21‐activated kinase 1 (PAK1) plays key roles in cellular processes including proliferation, survival, and motility, and in cell transformation and tumor progression. PAK1 expression increases with the progression of CRC, and knockdown of PAK1 blocks CRC cell growth and metastasis both in vitro and in vivo. The aim of this study was to determine the interaction between PAK1 and gastrins in CRC cells. PAK1 expression and activation were assayed by Western blots, and concentrations of gastrin mRNA and peptides by real‐time PCR and radioimmunoassay, respectively. Proliferation of CRC cells was measured by 3H‐thymidine incorporation, and vascular endothelial growth factor (VEGF) secretion was measured by ELISA. Gastrins activated PAK1 via PI3K‐dependent pathways. Activated PAK1 in turn mediated gastrin‐stimulated activation of β‐catenin and VEGF secretion in CRC cells, as knockdown of PAK1 blocked stimulation of these cellular processes by gastrins. Downregulation of gastrin reduced the expression and activity of PAK1, but in contrast there was a compensatory increase in gastrins either when PAK1 was downregulated, or after treatment with a PAK inhibitor. Our results indicate that PAK1 is required for the stimulation of CRC cells by gastrins, and suggest the existence of an inhibitory feedback loop by which PAK1 downregulates gastrin production in CRC cells. PMID:24963032

  11. Computational Tools for Stem Cell Biology. (United States)

    Bian, Qin; Cahan, Patrick


    For over half a century, the field of developmental biology has leveraged computation to explore mechanisms of developmental processes. More recently, computational approaches have been critical in the translation of high throughput data into knowledge of both developmental and stem cell biology. In the past several years, a new subdiscipline of computational stem cell biology has emerged that synthesizes the modeling of systems-level aspects of stem cells with high-throughput molecular data. In this review, we provide an overview of this new field and pay particular attention to the impact that single cell transcriptomics is expected to have on our understanding of development and our ability to engineer cell fate. Copyright © 2016 Elsevier Ltd. All rights reserved.

  12. Cell biology of prokaryotic organelles. (United States)

    Murat, Dorothee; Byrne, Meghan; Komeili, Arash


    Mounting evidence in recent years has challenged the dogma that prokaryotes are simple and undefined cells devoid of an organized subcellular architecture. In fact, proteins once thought to be the purely eukaryotic inventions, including relatives of actin and tubulin control prokaryotic cell shape, DNA segregation, and cytokinesis. Similarly, compartmentalization, commonly noted as a distinguishing feature of eukaryotic cells, is also prevalent in the prokaryotic world in the form of protein-bounded and lipid-bounded organelles. In this article we highlight some of these prokaryotic organelles and discuss the current knowledge on their ultrastructure and the molecular mechanisms of their biogenesis and maintenance.

  13. A new prospect in cancer therapy: targeting cancer stem cells to eradicate cancer (United States)

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


    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. PMID:22507219

  14. Interfacing nanostructures to biological cells

    Energy Technology Data Exchange (ETDEWEB)

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


    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.

  15. Characterizing cancer cells with cancer stem cell-like features in 293T human embryonic kidney cells. (United States)

    Debeb, Bisrat G; Zhang, Xiaomei; Krishnamurthy, Savitri; Gao, Hui; Cohen, Evan; Li, Li; Rodriguez, Angel A; Landis, Melissa D; Lucci, Anthony; Ueno, Naoto T; Robertson, Fredika; Xu, Wei; Lacerda, Lara; Buchholz, Thomas A; Cristofanilli, Massimo; Reuben, James M; Lewis, Michael T; Woodward, Wendy A


    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 by serial xenograft passages through transplantation. Herein we fully characterize cancer stem cell-like features in 293T human embryonic kidney cells. 293T cells can be readily cultured and passaged as spheres in serum-free stem cell promoting culture conditions. Cells cultured in vitro as three-dimensional spheres (3D) were shown to contain higher ALDH1 and CD44+/CD24- population compared to monolayer cells. These cells were also resistant to radiation and upregulate stem cell survival signaling including beta-catenin, Notch1 and Survivin in response to radiation. Moreover, 3D spheres generated from the 293T cells have increased expression of mesenchymal genes including vimentin, n-cadherin, zeb1, snail and slug as well as pro-metastatic genes RhoC, Tenascin C and MTA1. In addition, microRNAs implicated in self-renewal and metastases were markedly reduced in 3D spheres. 293T cells exhibit a cancer stem cell-like phenotype when cultured as 3D spheres and represent an important research tool for studying the molecular and biological mechanisms of cancer stem cells and for testing and developing novel targets for cancer therapy.

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

    Directory of Open Access Journals (Sweden)

    Md. Al Mamun


    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.



    Hussein, Yaser R.; Sood, Anil K.; Bandyopadhyay, Sudeshna; Albashiti, Bassam; Semaan, Assaad; Nahleh, Zeina; Roh, Juwon; Han, Hee Dong; Lopez-Berestein, Gabriel; Ali-Fehmi, Rouba


    The polycomb group protein, enhancer of zeste homolog 2 (EZH2), is a transcriptional repressor involved in cell cycle regulation and has been linked to aggressive breast cancer. We examined the clinical and biological significance of EZH2 expression in triple-negative breast cancers. Tissue microarrays were constructed with invasive breast cancer cases and stained with EZH2, cytokeratin 5/6, epidermal growth factor receptor 1(EGFR) and p53. The expression of these markers was correlated with ...

  18. Modelos experimentais em oncologia: O contributo da cultura de células para o conhecimento da biologia do cancro Experimental models in oncology: Contribution of cell culture on understanding the biology of cancer

    Directory of Open Access Journals (Sweden)

    Mariana Cruz


    Full Text Available A cultura de tecidos surgiu no século xx (Harrison, 1907 para estudar o comportamento das células animais em ambiente homeostático e em situações de stress. A capacidade de estudar as células a nível molecular relaciona-se com a forma como as células podem crescer e ser manipuladas em laboratório. A cultura de células in vitro permitiu estudar crescimento, diferenciação e morte celular e efectuar manipulações genéticas necessárias ao perfeito conhecimento da estrutura e funções dos genes. A cultura de células estaminais humanas veio colmatar algumas limitações inerentes aos restantes modelos de cultura. Ao que parece, as células estaminais cancerígenas mantêm-se quiescentes nos locais metastáticos até serem activadas por sinais apropriados do microambiente. Vários estudos revelaram que diferentes tipos de cancros podem surgir da transformação maligna de células estaminais. A eliminação destas células progenitoras tumorais é essencial para o desenvolvimento de novas abordagens terapêuticas mais eficazes em cancros agressivos. Por outro lado, a utilização de células dendríticas modificadas em cultura poderá contribuir para a produção de uma potencial vacina terapêutica eficaz para obter a regressão tumoral.In the beginning of the 20th century, tissue culture was started with the aim of studying the behaviour of animal cells in normal and stress conditions. The cell study at molecular level depends on their capacity of growing and how they can be manipulated in laboratory. In vitro cell culture allows us the possibility of studying biological key processes, such as growth, differentiation and cell death, and also to do genetic manipulations essential to the knowledge of structure and genes function. Human stem cells culture provides strategies to circumvent other models’ deficiencies. It seems that cancer stem cells remain quiescent until activation by appropriated micro-environmental stimulation

  19. Cell Biology of Hyphal Growth. (United States)

    Steinberg, Gero; Peñalva, Miguel A; Riquelme, Meritxell; Wösten, Han A; Harris, Steven D


    Filamentous fungi are a large and ancient clade of microorganisms that occupy a broad range of ecological niches. The success of filamentous fungi is largely due to their elongate hypha, a chain of cells, separated from each other by septa. Hyphae grow by polarized exocytosis at the apex, which allows the fungus to overcome long distances and invade many substrates, including soils and host tissues. Hyphal tip growth is initiated by establishment of a growth site and the subsequent maintenance of the growth axis, with transport of growth supplies, including membranes and proteins, delivered by motors along the cytoskeleton to the hyphal apex. Among the enzymes delivered are cell wall synthases that are exocytosed for local synthesis of the extracellular cell wall. Exocytosis is opposed by endocytic uptake of soluble and membrane-bound material into the cell. The first intracellular compartment in the endocytic pathway is the early endosomes, which emerge to perform essential additional functions as spatial organizers of the hyphal cell. Individual compartments within septated hyphae can communicate with each other via septal pores, which allow passage of cytoplasm or organelles to help differentiation within the mycelium. This article introduces the reader to more detailed aspects of hyphal growth in fungi.

  20. Microfluidic tools for cell biological research (United States)

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


    Summary 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. PMID:21152269

  1. Nonequilibrium population dynamics of phenotype conversion of cancer cells.

    Directory of Open Access Journals (Sweden)

    Joseph Xu Zhou

    Full Text Available Tumorigenesis is a dynamic biological process that involves distinct cancer cell subpopulations proliferating at different rates and interconverting between them. In this paper we proposed a mathematical framework of population dynamics that considers both distinctive growth rates and intercellular transitions between cancer cell populations. Our mathematical framework showed that both growth and transition influence the ratio of cancer cell subpopulations but the latter is more significant. We derived the condition that different cancer cell types can maintain distinctive subpopulations and we also explain why there always exists a stable fixed ratio after cell sorting based on putative surface markers. The cell fraction ratio can be shifted by changing either the growth rates of the subpopulations (Darwinism selection or by environment-instructed transitions (Lamarckism induction. This insight can help us to understand the dynamics of the heterogeneity of cancer cells and lead us to new strategies to overcome cancer drug resistance.


    DEFF Research Database (Denmark)


    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...

  3. Cell biology of mitotic recombination

    DEFF Research Database (Denmark)

    Lisby, Michael; Rothstein, Rodney


    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...

  4. Epigenetics in cancer stem cells. (United States)

    Toh, Tan Boon; Lim, Jhin Jieh; Chow, Edward Kai-Hua


    Compelling evidence have demonstrated that bulk tumors can arise from a unique subset of cells commonly termed "cancer stem cells" that has been proposed to be a strong driving force of tumorigenesis and a key mechanism of therapeutic resistance. Recent advances in epigenomics have illuminated key mechanisms by which epigenetic regulation contribute to cancer progression. In this review, we present a discussion of how deregulation of various epigenetic pathways can contribute to cancer initiation and tumorigenesis, particularly with respect to maintenance and survival of cancer stem cells. This information, together with several promising clinical and preclinical trials of epigenetic modulating drugs, offer new possibilities for targeting cancer stem cells as well as improving cancer therapy overall.

  5. Lung cancer - non-small cell (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 ...

  6. Cell biology experiments conducted in space (United States)

    Taylor, G. R.


    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.

  7. Molecular biology of pancreatic cancer: how useful is it in clinical practice? (United States)

    Sakorafas, George H; Smyrniotis, Vasileios


    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. To critically present currently available data regarding clinical application of molecular biology in pancreatic cancer. 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. 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. 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 in pancreatic cancer will expand in the future, improving the

  8. Biological synthesis of silver nanoparticles using the fungus Humicola sp. and evaluation of their cytoxicity using normal and cancer cell lines. (United States)

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


    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. Copyright © 2013 Elsevier B.V. All rights reserved.

  9. [The role of cancer stem cells in progressive growth and resistance of ovarian cancer: true or fiction?]. (United States)

    Bar, Julia K; Grelewski, Piotr; Lis-Nawara, Anna; Drobnikowska, Kamila


    Growing evidence indicates that biological heterogeneity of ovarian cancer is associated with a small subpopulation of cancer cells existing within tumor tissue and defined as cancer stem cells (CSCs). This small group of ovarian cells possesses the capacity of self-renewal. Recent data revealed that progression, metastasis and relapse of ovarian cancers are related to the behavior of cancer stem cells. However, how ovarian CSCs maintain their migration properties is still unclear. The clinical relevance of CSCs has been supported by emerging evidence, showing that CSCs are resistant to conventional chemotherapy of ovarian cancer. Identification of biomarkers of ovarian cancer stem cells seems to be important for target therapy. Therapeutic strategies aimed at eliminating CSCs in ovarian cancers might extend disease survival and limit recurrence. This review will describe the current knowledge of ovarian CSCs biology and contribution of these cells to metastasis and chemoresistance of ovarian cancer as well as the possibility to use target therapy of ovarian CSCs.

  10. [Radiosensitivity and/or radioresistance of head and neck cancers: Biological angle]. (United States)

    Guy, Jean-Baptiste; Rancoule, Chloé; Méry, Benoîte; Espenel, Sophie; Wozny, Anne-Sophie; Simonet, Stéphanie; Vallard, Alexis; Alphonse, Gersende; Ardail, Dominique; Rodriguez-Lafrasse, Claire; Magné, Nicolas


    Radiation therapy is a cornerstone of head and neck cancer management. Technological improvements in recent years in radiation therapy, with intensity-modulated techniques, reinforce even more its role. However, both local and locoregional relapses are still observed. Understanding biological mechanisms of treatment resistance is a topic of major interest. From the cancer cell itself, its ability to repair and proliferate, its microenvironment and oxygenation conditions, migratory and invasive capacity, to biological parameters related to the patient, there are many mechanisms involving radiosensitivity and/or radioresistance of head and neck cancer. The present study explores the main biological mechanisms involved in radiation resistance of head and neck cancer, and describes promising therapeutic approaches. Copyright © 2015 Société Française du Cancer. Published by Elsevier Masson SAS. All rights reserved.

  11. Nanotechniques Inactivate Cancer Stem Cells (United States)

    Goltsev, Anatoliy N.; Babenko, Natalya N.; Gaevskaya, Yulia A.; Bondarovich, Nikolay A.; Dubrava, Tatiana G.; Ostankov, Maksim V.; Chelombitko, Olga V.; Malyukin, Yuriy V.; Klochkov, Vladimir K.; Kavok, Nataliya S.


    One of the tasks of current oncology is identification of cancer stem cells and search of therapeutic means capable of their specific inhibition. The paper presents the data on phenotype characteristics of Ehrlich carcinoma cells as convenient and easy-to-follow model of tumor growth. The evidence of cancer stem cells as a part of Ehrlich carcinoma and significance of CD44+ and CD44- subpopulations in maintaining the growth of this type of tumor were demonstrated. A high (tenfold) tumorigenic activity of the Ehrlich carcinoma CD44+ cells if compared to CD44- cells was proven. In this pair of comparison, the CD44+ cells had a higher potential of generating in peritoneal cavity of CD44high, CD44+CD24-, CD44+CD24+ cell subpopulations, highlighting the presence of cancer stem cells in a pool of CD44+ cells.

  12. Prion potency in stem cells biology. (United States)

    Lopes, Marilene H; Santos, Tiago G


    Prion protein (PrP) can be considered a pivotal molecule because it interacts with several partners to perform a diverse range of critical biological functions that might differ in embryonic and adult cells. In recent years, there have been major advances in elucidating the putative role of PrP in the basic biology of stem cells in many different systems. Here, we review the evidence indicating that PrP is a key molecule involved in driving different aspects of the potency of embryonic and tissue-specific stem cells in self-perpetuation and differentiation in many cell types. It has been shown that PrP is involved in stem cell self-renewal, controlling pluripotency gene expression, proliferation, and neural and cardiomyocyte differentiation. PrP also has essential roles in distinct processes that regulate tissue-specific stem cell biology in nervous and hematopoietic systems and during muscle regeneration. Results from our own investigations have shown that PrP is able to modulate self-renewal and proliferation in neural stem cells, processes that are enhanced by PrP interactions with stress inducible protein 1 (STI1). Thus, the available data reveal the influence of PrP in acting upon the maintenance of pluripotent status or the differentiation of stem cells from the early embryogenesis through adulthood.

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

    DEFF Research Database (Denmark)

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


    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...

  14. Are All Highly Malignant Cancer Cells Identical? (United States)


    ADA3665 ARE AL HIGHL MAGNANTCANCER CELLS DENOIALU) PENNSYLVANIA HOSPITAL PHILADELPHIA DEPT OF MOLECULAR BIOLOGY G NIGET AL 199 N00014-ACA026 UNCLASFE...embryo cells or even the original fertilized ovum . If this speculation has validity, the carcinogenesis and differentiation have the same destinies but...F/G /5 N 1111 2Z111117 1 125iiI 1 1. 1111_L6. -11 O=M 1 MrCROCOP RErSOLUTICN TEST CHART N, APoP SN A’ ,- ARE ALL HIGHLY MALIGNANT CANCER CELLS

  15. Countercurrent distribution of biological cells (United States)


    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.

  16. Multifaceted Interpretation of Colon Cancer Stem Cells


    Hatano, Yuichiro; Fukuda, Shinya; Hisamatsu, Kenji; Hirata, Akihiro; Hara, Akira; Tomita, Hiroyuki


    Colon cancer is one of the leading causes of cancer-related deaths worldwide, despite recent advances in clinical oncology. Accumulating evidence sheds light on the existence of cancer stem cells and their role in conferring therapeutic resistance. Cancer stem cells are a minor fraction of cancer cells, which enable tumor heterogeneity and initiate tumor formation. In addition, these cells are resistant to various cytotoxic factors. Therefore, elimination of cancer stem cells is difficult but...

  17. Systems Biology and Cancer Prevention: All Options on the Table

    Directory of Open Access Journals (Sweden)

    Simon Rosenfeld


    Full Text Available In this paper, we outline the status quo and approaches to further development of the systems biology concepts with focus on applications in cancer prevention science. We discuss the biological aspects of cancer research that are of primary importance in cancer prevention, motivations for their mathematical modeling and some recent advances in computational oncology. We also make an attempt to outline in big conceptual terms the contours of future work aimed at creation of large-scale computational and informational infrastructure for using as a routine tool in cancer prevention science and decision making.

  18. Biology and relevance of human acute myeloid leukemia stem cells. (United States)

    Thomas, Daniel; Majeti, Ravindra


    Evidence of human acute myeloid leukemia stem cells (AML LSCs) was first reported nearly 2 decades ago through the identification of rare subpopulations of engrafting cells in xenotransplantation assays. These AML LSCs were shown to reside at the apex of a cellular hierarchy that initiates and maintains the disease, exhibiting properties of self-renewal, cell cycle quiescence, and chemoresistance. This cancer stem cell model offers an explanation for chemotherapy resistance and disease relapse and implies that approaches to treatment must eradicate LSCs for cure. More recently, a number of studies have both refined and expanded our understanding of LSCs and intrapatient heterogeneity in AML using improved xenotransplant models, genome-scale analyses, and experimental manipulation of primary patient cells. Here, we review these studies with a focus on the immunophenotype, biological properties, epigenetics, genetics, and clinical associations of human AML LSCs and discuss critical questions that need to be addressed in future research. © 2017 by The American Society of Hematology.

  19. Engineering Therapeutic T Cells: From Synthetic Biology to Clinical Trials. (United States)

    Esensten, Jonathan H; Bluestone, Jeffrey A; Lim, Wendell A


    Engineered T cells are currently in clinical trials to treat patients with cancer, solid organ transplants, and autoimmune diseases. However, the field is still in its infancy. The design, and manufacturing, of T cell therapies is not standardized and is performed mostly in academic settings by competing groups. Reliable methods to define dose and pharmacokinetics of T cell therapies need to be developed. As of mid-2016, there are no US Food and Drug Administration (FDA)-approved T cell therapeutics on the market, and FDA regulations are only slowly adapting to the new technologies. Further development of engineered T cell therapies requires advances in immunology, synthetic biology, manufacturing processes, and government regulation. In this review, we outline some of these challenges and discuss the contributions that pathologists can make to this emerging field.

  20. Live cell imaging and systems biology (United States)

    Sung, Myong-Hee; McNally, James G


    Much of the experimental data used to construct mathematical models of molecular networks are derived from in vitro measurements. However, there is increasing evidence that in vitro measurements fail to capture both the complexity and the individuality found in single, living cells. These limitations can be overcome by live cell microscopy which is evolving to enable in vivo biochemistry. Here we survey the current capabilities of live cell microscopy and illustrate how a number of different imaging approaches could be applied to analyze a specific molecular network. We argue that incorporation of such quantitative live cell imaging methods is critical for the progress of systems biology. PMID:20730797

  1. Cancer biology and genomics: translating discoveries, transforming pathology. (United States)

    Ladanyi, Marc; Hogendoorn, Pancras C W


    Advances in our understanding of cancer biology and discoveries emerging from cancer genomics are being translated into real clinical benefits for patients with cancer. The 2011 Journal of Pathology Annual Review Issue provides a snapshot of recent rapid progress on multiple fronts in the war on cancer or, more precisely, the wars on cancers. Indeed, perhaps the most notable recent shift is reflected by the sharp increase in understanding the biology of multiple specific cancers and using these new insights to inform rationally targeted therapies, with often striking successes. These recent developments, as reviewed in this issue, show how the long-term investments in basic cancer research are finally beginning to bear fruit. Copyright © 2010 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

  2. 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 (United States)

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


    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

  3. Characterising Castrate Tolerant Prostate Cancer Cells




    Prostate cancer is a prevalent disease in aging males. This thesis explores prostate cancer cells that escape current therapy and give rise to end-stage disease. Using sophisticated experimental approaches, this important cancer cell population was identified and characterised in human prostate cancer tissues.  Our discoveries will eventually lead to improved cancer treatments for men with prostate cancer.

  4. Quantitative nano-mechanics of biological cells with AFM (United States)

    Sokolov, Igor


    The importance of study of living cells is hard to overestimate. Cell mechanics is a relatively young, yet not a well-developed area. Besides just a fundamental interest, large practical need has emerged to measure cell mechanics quantitatively. Recent studies revealed a significant correlation between stiffness of biological cells and various human diseases, such as cancer, malaria, arthritis, and even aging. However, really quantitative studies of mechanics of biological cells are virtually absent. It is not even clear if the cell, being a complex and heterogeneous object, can be described by the elastic modulus at all. Atomic force microscopy (AFM) is a natural instrument to study properties of cells in their native environments. Here we will demonstrate that quantitative measurements of elastic modulus of cells with AFM are possible. Specifically, we will show that the ``cell body'' (cell without ``brush'' surface layer, a non-elastic layer surrounding cells) typically demonstrates the response of a homogeneous elastic medium up to the deformation of 10-20%, but if and only if a) the cellular brush layer is taken into account, b) rather dull AFM probes are used. This will be justified with the help of the strong condition of elastic behavior of material: the elastic modulus is shown to be independent on the indentation depth. We will also demonstrate that an attempt either to ignore the brush layer or to use sharp AFM probes will result in the violation of the strong condition, which implies impossibility to use the concept of the elastic modulus to describe cell mechanics in such experiments. Examples of quantitative measurements of the Young's modulus of the cell body and the cell brush parameters will be given for various cells. Address when submitting: Clarkson University, Potsdam, NY 13699

  5. Role of the Microenvironment in Ovarian Cancer Stem Cell Maintenance

    Directory of Open Access Journals (Sweden)

    Jennifer Pasquier


    Full Text Available Despite recent progresses in cancer therapy and increased knowledge in cancer biology, ovarian cancer remains a challenging condition. Among the latest concepts developed in cancer biology, cancer stem cells and the role of microenvironment in tumor progression seem to be related. Indeed, cancer stem cells have been described in several solid tumors including ovarian cancers. These particular cells have the ability to self-renew and reconstitute a heterogeneous tumor. They are characterized by specific surface markers and display resistance to therapeutic regimens. During development, specific molecular cues from the tumor microenvironment can play a role in maintaining and expanding stemness of cancer cells. The tumor stroma contains several compartments: cellular component, cytokine network, and extracellular matrix. These different compartments interact to form a permissive niche for the cancer stem cells. Understanding the molecular cues underlying this crosstalk will allow the design of new therapeutic regimens targeting the niche. In this paper, we will discuss the mechanisms implicated in the interaction between ovarian cancer stem cells and their microenvironment.

  6. Diet & Cancer: An Update for Biology Teachers. (United States)

    Anastasiou, Clifford J.


    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)

  7. Developmental biology and the redirection or replacement of cells. (United States)

    Gurdon, J


    The aim of developmental biology is to understand how an egg converts itself into a complete organism through the processes of cell differentiation, morphogenesis and size regulation. The principles that have emerged over recent decades include the constancy of the genome in nearly all cells of an individual, the existence of stem cells in many organs and the overwhelming importance of signalling between cells for the determination of their fate. These and other characteristics of development are discussed here in relation to the prospect of achieving cell and tissue correction or replacement with the help of nuclear transplantation and signalling factors. Nuclear transplantation offers a one-step procedure for generating multipotent embryo cells from the cells of an adult tissue such as skin. It should be possible to proliferate the resulting cells as can be done for mouse embryonic stem cells. Embryo cells can be made to differentiate in many directions by exposing them to various agents or to different concentrations of a single factor such as the transforming growth factor beta class signalling molecule activin. The possibility of a cancerous condition being acquired during these experimental manipulations can be guarded against by transfecting cells with a conditional suicide gene. Thus it may be possible to generate replacement cells or tissues from an adult human for transplantation back to the original donor, without the disadvantage of any genetic incompatibility.

  8. Textbook Errors & Misconceptions in Biology: Cell Metabolism. (United States)

    Storey, Richard D.


    The idea that errors and misconceptions in biology textbooks are often slow to be discovered and corrected is discussed. Selected errors, misconceptions, and topics of confusion about cell metabolism are described. Fermentation, respiration, Krebs cycle, pentose phosphate pathway, uniformity of catabolism, and metabolic pathways as models are…

  9. New Materials for Biological Fuel Cells (United States)


    CBN-based bioelectrodes are found in the literature. Ma et al. immobilized hemoglobin on standard carbon black powders (reportedly 30 – 100 nm...dehydrogenase and PQQ- dependent glucose dehydrogenase-based biological fuel cells18. CBN are readily modified to create composites; emulsions of Teflon

  10. Defining key concepts of intestinal and epithelial cancer biology through the use of mouse models. (United States)

    Phesse, Toby J; Durban, Victoria Marsh; Sansom, Owen J


    Over the past 20 years, huge advances have been made in modelling human diseases such as cancer using genetically modified mice. Accurate in vivo models are essential to examine the complex interaction between cancer cells, surrounding stromal cells, tumour-associated inflammatory cells, fibroblast and blood vessels, and to recapitulate all the steps involved in metastasis. Elucidating these interactions in vitro has inherent limitations, and thus animal models are a powerful tool to enable researchers to gain insight into the complex interactions between signalling pathways and different cells types. This review will focus on how advances in in vivo models have shed light on many aspects of cancer biology including the identification of oncogenes, tumour suppressors and stem cells, epigenetics, cell death and context dependent cell signalling. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please email:

  11. An electrostatic model for biological cell division

    CERN Document Server

    Faraggi, Eshel


    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...

  12. Natural biology and management of nonmuscle invasive bladder cancer

    DEFF Research Database (Denmark)

    Scarpato, Kristen R; Tyson, Mark D; Clark, Peter E


    PURPOSE OF REVIEW: This article reviews the natural biology of noninvasive bladder cancer and its management strategies while summarizing the most recent advances in the field. RECENT FINDINGS: Nonmuscle invasive bladder cancer (NMIBC) has a tendency to recur and progress. Risk stratification has...... in low-risk patients. SUMMARY: NMIBC represents a variety of disease states and continues to pose management challenges. As our understanding of tumor biology improves and technology advances, achieving better outcomes through individualized care may be possible....

  13. Recent development on synthetic biological devices treating bladder cancer


    Chen, Zhicong; He, Anbang; Liu, Yuchen; Huang, Weiren; Cai, Zhiming


    Synthetic biology is an emerging field focusing on engineering genetic devices and biomolecular systems for a variety of applications from basic biology to biotechnology and medicine. Thanks to the tremendous advances in genomics and the chemical synthesis of DNA in the past decade, scientists are now able to engineer genetic devices and circuits for cancer research and intervention, which offer promising therapeutic strategies for cancer treatment. In this article, we provide a systemic revi...

  14. Basic principles of tumor-associated regulatory T cell biology. (United States)

    Savage, Peter A; Malchow, Sven; Leventhal, Daniel S


    Due to the critical role of forkhead box (Fox)p3(+) regulatory T cells (Tregs) in the regulation of immunity and the enrichment of Tregs within many human tumors, several emerging therapeutic strategies for cancer involve the depletion or modulation of Tregs, with the aim of eliciting enhanced antitumor immune responses. Here, we review recent advances in understanding of the fundamental biology of Tregs, and discuss the implications of these findings for current models of tumor-associated Treg biology. In particular, we discuss the context-dependent functional diversity of Tregs, the developmental origins of these cells, and the nature of the antigens that they recognize within the tumor environment. In addition, we highlight critical areas of focus for future research. Copyright © 2012 Elsevier Ltd. All rights reserved.

  15. Single cancer cell analysis on a chip

    NARCIS (Netherlands)

    Yang, Yoon Sun


    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

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

    Directory of Open Access Journals (Sweden)

    Maciej Jankowski


    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.

  17. Atlas of Cancer Signalling Network: a systems biology resource for integrative analysis of cancer data with Google Maps. (United States)

    Kuperstein, I; Bonnet, E; Nguyen, H-A; Cohen, D; Viara, E; Grieco, L; Fourquet, S; Calzone, L; Russo, C; Kondratova, M; Dutreix, M; Barillot, E; Zinovyev, A


    Cancerogenesis is driven by mutations leading to aberrant functioning of a complex network of molecular interactions and simultaneously affecting multiple cellular functions. Therefore, the successful application of bioinformatics and systems biology methods for analysis of high-throughput data in cancer research heavily depends on availability of global and detailed reconstructions of signalling networks amenable for computational analysis. We present here the Atlas of Cancer Signalling Network (ACSN), an interactive and comprehensive map of molecular mechanisms implicated in cancer. The resource includes tools for map navigation, visualization and analysis of molecular data in the context of signalling network maps. Constructing and updating ACSN involves careful manual curation of molecular biology literature and participation of experts in the corresponding fields. The cancer-oriented content of ACSN is completely original and covers major mechanisms involved in cancer progression, including DNA repair, cell survival, apoptosis, cell cycle, EMT and cell motility. Cell signalling mechanisms are depicted in detail, together creating a seamless 'geographic-like' map of molecular interactions frequently deregulated in cancer. The map is browsable using NaviCell web interface using the Google Maps engine and semantic zooming principle. The associated web-blog provides a forum for commenting and curating the ACSN content. ACSN allows uploading heterogeneous omics data from users on top of the maps for visualization and performing functional analyses. We suggest several scenarios for ACSN application in cancer research, particularly for visualizing high-throughput data, starting from small interfering RNA-based screening results or mutation frequencies to innovative ways of exploring transcriptomes and phosphoproteomes. Integration and analysis of these data in the context of ACSN may help interpret their biological significance and formulate mechanistic hypotheses

  18. Epigenetics Meets Radiation Biology as a New Approach in Cancer Treatment

    Directory of Open Access Journals (Sweden)

    Joo Mi Yi


    Full Text Available Cancer is a disease that results from both genetic and epigenetic changes. In recent decades, a number of people have investigated the disparities in gene expression resulting from variable DNA methylation alteration and chromatin structure modification in response to the environment. Especially, colon cancer is a great model system for investigating the epigenetic mechanism for aberrant gene expression alteration. Ionizing radiation (IR could affect a variety of processes within exposed cells and, in particular, cause changes in gene expression, disruption of cell cycle arrest, and apoptotic cell death. Even though there is growing evidence on the importance of epigenetics and biological processes induced by radiation exposure in various cancer types including colon cancer, specific epigenetic alterations induced by radiation at the molecular level are incompletely defined. This review focuses on discussing possible IR-mediated changes of DNA methylation and histone modification in cancer.

  19. Epigenetics meets radiation biology as a new approach in cancer treatment. (United States)

    Kim, Joong-Gook; Park, Moon-Taek; Heo, Kyu; Yang, Kwang-Mo; Yi, Joo Mi


    Cancer is a disease that results from both genetic and epigenetic changes. In recent decades, a number of people have investigated the disparities in gene expression resulting from variable DNA methylation alteration and chromatin structure modification in response to the environment. Especially, colon cancer is a great model system for investigating the epigenetic mechanism for aberrant gene expression alteration. Ionizing radiation (IR) could affect a variety of processes within exposed cells and, in particular, cause changes in gene expression, disruption of cell cycle arrest, and apoptotic cell death. Even though there is growing evidence on the importance of epigenetics and biological processes induced by radiation exposure in various cancer types including colon cancer, specific epigenetic alterations induced by radiation at the molecular level are incompletely defined. This review focuses on discussing possible IR-mediated changes of DNA methylation and histone modification in cancer.

  20. Analysis of undergraduate cell biology contents in Brazilian public universities. (United States)

    Mermelstein, Claudia; Costa, Manoel Luis


    The enormous amount of information available in cell biology has created a challenge in selecting the core concepts we should be teaching our undergraduates. One way to define a set of essential core ideas in cell biology is to analyze what a specific cell biology community is teaching their students. Our main objective was to analyze the cell biology content currently being taught in Brazilian universities. We collected the syllabi of cell biology courses from public universities in Brazil and analyzed the frequency of cell biology topics in each course. We also compared the Brazilian data with the contents of a major cell biology textbook. Our analysis showed that while some cell biology topics such as plasma membrane and cytoskeleton was present in ∼100% of the Brazilian curricula analyzed others such as cell signaling and cell differentiation were present in only ∼35%. The average cell biology content taught in the Brazilian universities is quite different from what is presented in the textbook. We discuss several possible explanations for these observations. We also suggest a list with essential cell biology topics for any biological or biomedical undergraduate course. The comparative discussion of cell biology topics presented here could be valuable in other educational contexts. © 2017 The Authors. Cell Biology International Published by John Wiley & Sons Ltd on behalf of International Federation of Cell Biology.

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

    Directory of Open Access Journals (Sweden)

    Ying ZHUO


    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

  2. Induction of iPS cells and of cancer stem cells: the stem cell or reprogramming hypothesis of cancer? (United States)

    Trosko, James E


    This article as designed to examine whether the "stoichiometric" or "elite models" of the origin of the "induced pluripotent stem" (iPS) cells fits some experiment facts from the developmental biology of adult stem cells and from the field of cancer research. In brief, since the evidence presented to support the stoichiometric model failed to recognize the factual existence of adult organ specific stem cells, the model has not been rigorously tested. In addition, the demonstration of a subset of cells (MUSE cells) in normal primary in vitro cultures of human fibroblasts (the usual source of iPS cells) seems to be the origin of the iPS cells. Moreover, from the field of carcinogenesis, the "stem cell" versus "de-differentiation" or "reprogramming" hypotheses were examined. Again, using the role of glycolysis, known to be associated with the Warburg effect in cancer cells, a list of experiments showing that (a) normal stem cells, which have few mitochondria, metabolize via glycolysis; (b) the stem cells are targets for "initiation" or "immortalization" or the blockage of differentiation and apoptosis of the stem cells by "immortalizing viruses"; (c) Lactate dehydrogenase A (LDHA), when expressed, is associated with glycolysis and therefore, must be expressed in normal adult stem cells, as well as in cancer cells; and (d) p53, depleted or rendered dysfunctional by SV40 Large T antigen, is associated with the reduction of mitochondrial function and mass and is associated with the Warburg effect. Together, these observations from the iPS and "cancer stem cell" fields support the idea that both iPS cells and cancer stem cell are derived from adult organ-specific stem cells that do not restore or switch their metabolism of glucose from oxidative metabolism to glycolysis but, rather, in both cases, the adult stem cell, which metabolizes by glycolysis, is prevented from differentiation or from metabolizing by oxidative phosphorylation. Copyright © 2013 Wiley Periodicals

  3. [Molecular biology in the development of colorectal cancer]. (United States)

    Nagawa, H; Muto, T


    In 1988, Vogelstein and colleagues published a paper entitled "Genetic alterations during colorectal-tumor development." This marked the beginning of a series of advances in our understanding of how colorectal cancer develops. This paper also provided evidence for the adenoma-carcinoma sequence. Furthermore, the importance of DNA mismatch repair genes in hereditary nonpolyposis colorectal cancer has been recognized. We herein discuss the development of colorectal cancer on the basis of molecular biology, including specific abnormalities of related genes.

  4. NCI RNA Biology 2017 symposium recap | Center for Cancer Research (United States)

    The recent discovery of new classes of RNAs and the demonstration that alterations in RNA metabolism underlie numerous human cancers have resulted in enormous interest among CCR investigators in RNA biology. In order to share the latest research in this exciting field, the CCR Initiative in RNA Biology held its second international symposium April 23-24, 2017, in Natcher Auditorium. Learn more...

  5. The Anti-Cancer Effect of Polyphenols against Breast Cancer and Cancer Stem Cells: Molecular Mechanisms

    Directory of Open Access Journals (Sweden)

    Ahmed Abdal Dayem


    Full Text Available The high incidence of breast cancer in developed and developing countries, and its correlation to cancer-related deaths, has prompted concerned scientists to discover novel alternatives to deal with this challenge. In this review, we will provide a brief overview of polyphenol structures and classifications, as well as on the carcinogenic process. The biology of breast cancer cells will also be discussed. The molecular mechanisms involved in the anti-cancer activities of numerous polyphenols, against a wide range of breast cancer cells, in vitro and in vivo, will be explained in detail. The interplay between autophagy and apoptosis in the anti-cancer activity of polyphenols will also be highlighted. In addition, the potential of polyphenols to target cancer stem cells (CSCs via various mechanisms will be explained. Recently, the use of natural products as chemotherapeutics and chemopreventive drugs to overcome the side effects and resistance that arise from using chemical-based agents has garnered the attention of the scientific community. Polyphenol research is considered a promising field in the treatment and prevention of breast cancer.

  6. Cancer Systems Biology Consortium | Informatics Technology for Cancer Research (ITCR) (United States)

    Cancer is a complex disease system involving multiple molecular, genetic, and cellular events. From its early initiation through progression and metastasis, cancer can adapt and evolve as a result of both internal and external signals. These properties make cancer difficult to predict, prevent, and treat. There has been significant progress in characterizing the genetics of cancer, as well as the downstream effects on the molecular and cellular pathways that are critical for the initiation and progression of cancer.

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

    Directory of Open Access Journals (Sweden)

    Yee Cassian


    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.

  8. Correlation between serum tryptase, mast cells positive to tryptase and microvascular density in colo-rectal cancer patients: possible biological-clinical significance.

    Directory of Open Access Journals (Sweden)

    Michele Ammendola

    Full Text Available BACKGROUND: Tryptase is a serin protease stored and released from mast cells (MCs that plays a role in tumour angiogenesis. In this study we aimed to evaluate serum tryptase levels in colo-rectal cancer (CRC patients before (STLBS and after (STLAS radical surgical resection. We also evaluated mast cell density positive to tryptase (MCDPT and microvascular density (MVD in primary tumour tissue. METHODS: A series of 61 patients with stage B and C CRC (according to the Astler and Coller staging system were selected. Serum blood samples were collected from patients one day before and one day after surgery. Tryptase levels were measured using the UniCAP Tryptase Fluoroenzymeimmunoassay (Pharmacia, Uppsala, Sweden. Tumour sections were immunostained with a primary anti-tryptase antibody (clone AA1; Dako, Glostrup, Denmark and an anti CD-34 antibody (QB-END 10; Bio-Optica Milan, Italy by means of immunohistochemistry and then evaluated by image analysis methods. RESULTS: The mean ± s.d. STLBS and STLAS was 5.63±2.61 µg/L, and 3.39±1.47 µg/L respectively and a significant difference between mean levels was found: p = 0.000 by t-test. The mean ± s.d. of MCDPT and MVD was 8.13±3.28 and 29.16±7.39 respectively. A strong correlation between STLBS and MVD (r = 0.83, p = 0.000; STLBS and MCDPT (r = 0.60, p = 0.003; and MCDPT and MVD (r = 0.73; p = 0.001 was found. CONCLUSION: Results demonstrated higher STLBS in CRC patients, indicating an involvement of MC tryptase in CRC angiogenesis. Data also indicated lower STLAS, suggesting the release of tryptase from tumour-infiltrating MCs. Serum tryptase levels may therefore play a role as a novel bio-marker predictive of response to radical surgery. In this context tryptase inhibitors such as Gabexate and Nafamostat Mesilate might be evaluated in adjuvant clinical trials as a new anti-angiogenic approach.

  9. Cancer stem cell: fundamental experimental pathological concepts and updates. (United States)

    Islam, Farhadul; Qiao, Bin; Smith, Robert A; Gopalan, Vinod; Lam, Alfred K-Y


    Cancer stem cells (CSCs) are a subset of cancer cells which play a key role in predicting the biological aggressiveness of cancer due to its ability of self-renewal and multi-lineage differentiation (stemness). The CSC model is a dynamic one with a functional subpopulation of cancer cells rather than a stable cell population responsible for tumour regeneration. Hypotheses regarding the origins of CSCs include (1) malignant transformation of normal stem cells; (2) mature cancer cell de-differentiation with epithelial-mesenchymal transition and (3) induced pluripotent cancer cells. Surprisingly, the cancer stem cell hypothesis originated in the late nineteenth century and the existence of haematopoietic stem cells was demonstrated a century later, demonstrating that the concept was possible. In the last decade, CSCs have been identified and isolated in different cancers. The hallmark traits of CSCs include their heterogeneity, interaction with microenvironments and plasticity. Understanding these basic concepts of CSCs is important for translational applications using CSCs in the management of patients with cancer. Copyright © 2015 Elsevier Inc. All rights reserved.

  10. Molecular Biology and Prevention of Endometrial Cancer

    National Research Council Canada - National Science Library

    Maxwell, George L


    To increase our understanding of the molecular aberrations associated with endometrial carcinogenesis and the biologic mechanisms underlying the protective effect of oral contraceptive therapy. Methods: 1...

  11. Molecular Biology and Prevention of Endometrial Cancer

    National Research Council Canada - National Science Library

    Maxwell, George


    To increase our understanding of the molecular aberrations associated with endometrial carcinogenesis and the biologic mechanisms underlying the protective effect of oral contraceptive therapy. Methods: 1...

  12. Molecular Biology and Prevention of Endometrial Cancer

    National Research Council Canada - National Science Library

    Maxwell, George L


    To increase our understanding of the molecular aberrations associated with endometrial carcinogenesis and the biologic mechanisms underlying the protective effect of oral contraceptive (OC) therapy. 1...

  13. New York esophageal squamous cell carcinoma-1 and cancer immunotherapy. (United States)

    Esfandiary, Ali; Ghafouri-Fard, Soudeh


    New York esophageal squamous cell carcinoma 1 (NY-ESO-1) is a known cancer testis gene with exceptional immunogenicity and prevalent expression in many cancer types. These characteristics have made it an appropriate vaccine candidate with the potential application against various malignancies. This article reviews recent knowledge about the NY-ESO-1 biology, function, immunogenicity and expression in cancers as well as and the results of clinical trials with this antigen.

  14. Recent advances in lung cancer biology

    Energy Technology Data Exchange (ETDEWEB)

    Lechner, J.


    This paper provides an overview of carcinogenesis, especially as related to lung cancers. Various growth factors and their mutated forms as oncogenes are discussed with respect to gene location and their role in the oncogenic process. Finally the data is related to lung cancer induction in uranium miners and exposure to radon.

  15. Integrative miRNA-Gene Expression Analysis Enables Refinement of Associated Biology and Prediction of Response to Cetuximab in Head and Neck Squamous Cell Cancer

    Directory of Open Access Journals (Sweden)

    Loris De Cecco


    Full Text Available This paper documents the process by which we, through gene and miRNA expression profiling of the same samples of head and neck squamous cell carcinomas (HNSCC and an integrative miRNA-mRNA expression analysis, were able to identify candidate biomarkers of progression-free survival (PFS in patients treated with cetuximab-based approaches. Through sparse partial least square–discriminant analysis (sPLS-DA and supervised analysis, 36 miRNAs were identified in two components that clearly separated long- and short-PFS patients. Gene set enrichment analysis identified a significant correlation between the miRNA first-component and EGFR signaling, keratinocyte differentiation, and p53. Another significant correlation was identified between the second component and RAS, NOTCH, immune/inflammatory response, epithelial–mesenchymal transition (EMT, and angiogenesis pathways. Regularized canonical correlation analysis of sPLS-DA miRNA and gene data combined with the MAGIA2 web-tool highlighted 16 miRNAs and 84 genes that were interconnected in a total of 245 interactions. After feature selection by a smoothed t-statistic support vector machine, we identified three miRNAs and five genes in the miRNA-gene network whose expression result was the most relevant in predicting PFS (Area Under the Curve, AUC = 0.992. Overall, using a well-defined clinical setting and up-to-date bioinformatics tools, we are able to give the proof of principle that an integrative miRNA-mRNA expression could greatly contribute to the refinement of the biology behind a predictive model.

  16. Integrative miRNA-Gene Expression Analysis Enables Refinement of Associated Biology and Prediction of Response to Cetuximab in Head and Neck Squamous Cell Cancer (United States)

    De Cecco, Loris; Giannoccaro, Marco; Marchesi, Edoardo; Bossi, Paolo; Favales, Federica; Locati, Laura D.; Licitra, Lisa; Pilotti, Silvana; Canevari, Silvana


    This paper documents the process by which we, through gene and miRNA expression profiling of the same samples of head and neck squamous cell carcinomas (HNSCC) and an integrative miRNA-mRNA expression analysis, were able to identify candidate biomarkers of progression-free survival (PFS) in patients treated with cetuximab-based approaches. Through sparse partial least square–discriminant analysis (sPLS-DA) and supervised analysis, 36 miRNAs were identified in two components that clearly separated long- and short-PFS patients. Gene set enrichment analysis identified a significant correlation between the miRNA first-component and EGFR signaling, keratinocyte differentiation, and p53. Another significant correlation was identified between the second component and RAS, NOTCH, immune/inflammatory response, epithelial–mesenchymal transition (EMT), and angiogenesis pathways. Regularized canonical correlation analysis of sPLS-DA miRNA and gene data combined with the MAGIA2 web-tool highlighted 16 miRNAs and 84 genes that were interconnected in a total of 245 interactions. After feature selection by a smoothed t-statistic support vector machine, we identified three miRNAs and five genes in the miRNA-gene network whose expression result was the most relevant in predicting PFS (Area Under the Curve, AUC = 0.992). Overall, using a well-defined clinical setting and up-to-date bioinformatics tools, we are able to give the proof of principle that an integrative miRNA-mRNA expression could greatly contribute to the refinement of the biology behind a predictive model. PMID:28098823

  17. How cancer cells dictate their microenvironment: present roles of extracellular vesicles. (United States)

    Naito, Yutaka; Yoshioka, Yusuke; Yamamoto, Yusuke; Ochiya, Takahiro


    Intercellular communication plays an important role in cancer initiation and progression through secretory molecules, including growth factors and cytokines. Recent advances have revealed that small membrane vesicles, termed extracellular vesicles (EVs), served as a regulatory agent in the intercellular communication of cancer. EVs enable the transfer of functional molecules, including proteins, mRNA and microRNAs (miRNAs), into recipient cells. Cancer cells utilize EVs to dictate the unique phenotype of surrounding cells, thereby promoting cancer progression. Against such "education" by cancer cells, non-tumoral cells suppress cancer initiation and progression via EVs. Therefore, researchers consider EVs to be important cues to clarify the molecular mechanisms of cancer biology. Understanding the functions of EVs in cancer progression is an important aspect of cancer biology that has not been previously elucidated. In this review, we summarize experimental data that indicate the pivotal roles of EVs in cancer progression.

  18. From cell biology to biotechnology in space. (United States)

    Cogoli, A


    In this article I discuss the main results of our research in space biology from the simple early investigations with human lymphocytes in the early eighties until the projects in tissue engineering of the next decade on the international space station ISS. The discovery that T lymphocyte activation is nearly totally depressed in vitro in 0 g conditions showed that mammalian single cells are sensitive to the gravitational environment. Such finding had important implications in basic research, medicine and biotechnology. Low gravity can be used as a tool to investigate complicated and still obscure biological process from a new perspective not available to earth-bound laboratories. Low gravity may also favor certain bioprocesses involving the growth of tissues and thus lead to commercial and medical applications. However, shortage of crew time and of other resources, lack of sophisticated instrumentation, safety constraints pose serious limits to biological endeavors in space laboratories.

  19. Cyclooxygenase-2: A Role in Cancer Stem Cell Survival and Repopulation of Cancer Cells during Therapy

    Directory of Open Access Journals (Sweden)

    Lisa Y. Pang


    Full Text Available Cyclooxygenase-2 (COX-2 is an inducible form of the enzyme that catalyses the synthesis of prostanoids, including prostaglandin E2 (PGE2, a major mediator of inflammation and angiogenesis. COX-2 is overexpressed in cancer cells and is associated with progressive tumour growth, as well as resistance of cancer cells to conventional chemotherapy and radiotherapy. These therapies are often delivered in multiple doses, which are spaced out to allow the recovery of normal tissues between treatments. However, surviving cancer cells also proliferate during treatment intervals, leading to repopulation of the tumour and limiting the effectiveness of the treatment. Tumour cell repopulation is a major cause of treatment failure. The central dogma is that conventional chemotherapy and radiotherapy selects resistant cancer cells that are able to reinitiate tumour growth. However, there is compelling evidence of an active proliferative response, driven by increased COX-2 expression and downstream PGE2 release, which contribute to the repopulation of tumours and poor patient outcome. In this review, we will examine the evidence for a role of COX-2 in cancer stem cell biology and as a mediator of tumour repopulation that can be molecularly targeted to overcome resistance to therapy.

  20. Myc mediates cancer stem-like cells and EMT changes in triple negative breast cancers cells.

    Directory of Open Access Journals (Sweden)

    Shuping Yin

    Full Text Available Women with triple negative breast cancer (TNBC have poor prognosis compared to other breast cancer subtypes. There were several reports indicating racial disparity in breast cancer outcomes between African American (AA and European American (EA women. For example, the mortality rates of AA breast cancer patients were three times higher than of EA patients, even though, the incidence is lower in AA women. Our in vitro studies indicate that cancer stem-like cells (CSCs derived from AA TNBC cell lines have significantly higher self-renewal potential (mammosphere formation than CSCs derived from EA cell lines. TNBC tumors express high levels of Myc compared to luminal A or HER2 expressing breast cancers. We studied the effects of c-Myc overexpression on CSCs and chemotherapy in AA, and EA derived TNBC cell line(s. Overexpression of c-Myc in AA derived MDA-MB-468 (Myc/MDA-468 cells resulted in a significant increase in CSCs and with minimal changes in epithelial-to-mesenchymal transition (EMT compared to the control group. In contrast, overexpression of c-Myc in EA derived MDA-MB-231(Myc/MDA-231 cells led to increased epithelial-to-mesenchymal transition (EMT, with a minimal increase in CSCs compared to the control group. Myc/MDA-468 cells were resistant to standard chemotherapeutic treatments such as iniparib (PARP inhibitor plus cisplatin, / iniparib, cisplatin, paclitaxel and docetaxel. However, Myc/MDA-231 cells, which showed EMT changes responded to iniparib with cisplatin, but were resistant to other drugs, such as iniparib, cisplatin, paclitaxel and docetaxel. Collectively, our results indicate that intrinsic differences in the tumor biology may contribute to the breast cancer disparities.

  1. From molecular to modular cell biology. (United States)

    Hartwell, L H; Hopfield, J J; Leibler, S; Murray, A W


    Cellular functions, such as signal transmission, are carried out by 'modules' made up of many species of interacting molecules. Understanding how modules work has depended on combining phenomenological analysis with molecular studies. General principles that govern the structure and behaviour of modules may be discovered with help from synthetic sciences such as engineering and computer science, from stronger interactions between experiment and theory in cell biology, and from an appreciation of evolutionary constraints.

  2. 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.


    The prognostic value of markers of cancer stem cells and epithelial to mesenchymal transition in small cell lung cancer is not known. We retrospectively studied these markers in the biopsy tissue of patients with small cell lung cancer and correlated them with overall survival and the strongest

  3. Brown seaweed fucoidan: biological activity and apoptosis, growth signaling mechanism in cancer. (United States)

    Senthilkumar, Kalimuthu; Manivasagan, Panchanathan; Venkatesan, Jayachandran; Kim, Se-Kwon


    Seaweeds, being abundant sources of bioactive components have much interest in recent times. The complex polysaccharides from the brown, red and green seaweeds possess broad spectrum therapeutic properties. The sulfated polysaccharides are routinely used in biomedical research and have known biological activities. Fucoidan, a fucose-rich polysaccharide extracted from brown seaweed has various biological functions including anticancer effects. Cellular damage induces growth arrest and tumor suppression by inducing apoptosis, the mechanism of cell death depends on the magnitude of DNA damage following exposure to anticancer agents. Apoptosis is mainly regulated by cell growth signaling molecules. Number of research studies evidenced that fucoidan shown to induce cytotoxicity of various cancer cells, induces apoptosis, and inhibits invasion, metastasis and angiogenesis of cancer cells. There are few articles discussing on fucoidan biological activity but no specific review on cancer and its signaling mechanism. Hence, this review discusses the brown seaweed fucoidan structure and some biological function and role in apoptosis, invasion, metastasis, angiogenesis and growth signal mechanism on cancer. Copyright © 2013 Elsevier B.V. All rights reserved.

  4. Autophagic regulation of smooth muscle cell biology

    Directory of Open Access Journals (Sweden)

    Joshua K. Salabei


    Full Text Available Autophagy regulates the metabolism, survival, and function of numerous cell types, including those comprising the cardiovascular system. In the vasculature, changes in autophagy have been documented in atherosclerotic and restenotic lesions and in hypertensive vessels. The biology of vascular smooth muscle cells appears particularly sensitive to changes in the autophagic program. Recent evidence indicates that stimuli or stressors evoked during the course of vascular disease can regulate autophagic activity, resulting in modulation of VSMC phenotype and viability. In particular, certain growth factors and cytokines, oxygen tension, and pharmacological drugs have been shown to trigger autophagy in smooth muscle cells. Importantly, each of these stimuli has a redox component, typically associated with changes in the abundance of reactive oxygen, nitrogen, or lipid species. Collective findings support the hypothesis that autophagy plays a critical role in vascular remodeling by regulating smooth muscle cell phenotype transitions and by influencing the cellular response to stress. In this graphical review, we summarize current knowledge on the role of autophagy in the biology of the smooth muscle cell in (pathophysiology.

  5. The changing world of modern cell biology (United States)

    Misteli, Tom


    Change is always ambiguous. There is the enticing prospect of novelty and better times ahead, but at the same time the concern of losing the good of the past. It is with these sentiments that I take over as the Editor-in-Chief from Ira Mellman who for a decade has cleverly and effectively lead the JCB. During this time he directed and oversaw an extensive modernization of the journal and guided it through dramatic changes in the publishing world. Ira lead the journal with unyielding dedication and enthusiasm and we in the cell biology community must thank him profoundly for his service. It is his work, together with the invaluable contribution of the best editorial board and the most dedicated professional editorial staff in the scientific publishing business, that allows me to now take over the stewardship of the JCB with a tremendous sense of excitement and determination to continue and expand the JCB's role as the leading journal in the cell biology community and as a trendsetter in the rapidly changing world of modern cell biology. PMID:19139259

  6. Chemical waves in cell and developmental biology. (United States)

    Deneke, Victoria E; Di Talia, Stefano


    Many biological events, such as the propagation of nerve impulses, the synchronized cell cycles of early embryogenesis, and collective cell migration, must be coordinated with remarkable speed across very large distances. Such rapid coordination cannot be achieved by simple diffusion of molecules alone and requires specialized mechanisms. Although active transport can provide a directed and efficient way to travel across subcellular structures, it cannot account for the most rapid examples of coordination found in biology. Rather, these appear to be driven by mechanisms involving traveling waves of chemical activities that are able to propagate information rapidly across biological or physical systems. Indeed, recent advances in our ability to probe the dynamics of signaling pathways are revealing many examples of coordination of cellular and developmental processes through traveling chemical waves. Here, we will review the theoretical principles underlying such waves; highlight recent literature on their role in different contexts, ranging from chemotaxis to development; and discuss open questions and future perspectives on the study of chemical waves as an essential feature of cell and tissue physiology. © 2018 Deneke and Di Talia.

  7. Biological Basis for Chemoprevention of Ovarian Cancer

    National Research Council Canada - National Science Library

    Berchuck, Andrew


    To achieve a better understanding of the etiology of ovarian cancer we have initiated a case-control study that considers genetic susceptibility epidemiologic risk factors and acquired genetic alterations...

  8. Circulating tumor cells: Exploring intratumor heterogeneity of colorectal cancer


    Raimondi, Cristina; Nicolazzo, Chiara; Gradilone, Angela; Giannini, Giuseppe; de Falco, Elena; Chimenti, Isotta; Varriale, Elisa; Hauch, Siegfried; Plappert, Linda; Cortesi, Enrico; Gazzaniga, Paola


    The hypothesis of the “liquid biopsy” using circulating tumor cells (CTCs) emerged as a minimally invasive alternative to traditional tissue biopsy to determine cancer therapy. Discordance for biomarkers expression between primary tumor tissue and circulating tumor cells (CTCs) has been widely reported, thus rendering the biological characterization of CTCs an attractive tool for biomarkers assessment and treatment selection. Studies performed in metastatic colorectal cancer (mCRC) patients u...

  9. Role of EZH2 in epithelial ovarian cancer: from biological insights to therapeutic target

    Directory of Open Access Journals (Sweden)

    Hua eLi


    Full Text Available EZH2 is the catalytic subunit of polycomb repressive complex 2 (PRC2, which generates a methylation epigenetic mark at lysine-27 residue of histone H3 (H3K27me3 to silence gene expression. EZH2 target genes are involved in a variety of biological processes such as stem cell pluripotency, cell proliferation and oncogenic transformation. EZH2 is often overexpressed in epithelial ovarian cancer cells and in ovarian cancer-associated stromal endothelial cells. Notably, EZH2 promotes cell proliferation, inhibits apoptosis and enhances angiogenesis in epithelial ovarian cancers. In contrast to genetic alterations, which are typically non-reversible, epigenetic alterations are reversible. Thus, inhibiting EZH2/PRC2 activity represents an attractive strategy for developing ovarian cancer therapeutics by targeting both ovarian cancer cells and ovarian tumor microenvironment. Here we discuss the progress recently obtained in understanding how EZH2/PRC2 promotes malignant phenotypes of epithelial ovarian cancer. In addition, we focus on strategies for targeting EZH2/PRC2 to develop novel epithelial ovarian cancer epigenetic therapeutics.

  10. Clinical and Biological Features of Interval Colorectal Cancer. (United States)

    Lee, Yu Mi; Huh, Kyu Chan


    Interval colorectal cancer (I-CRC) is defined as a CRC diagnosed within 60 months after a negative colonoscopy, taking into account that 5 years is the "mean sojourn time." It is important to prevent the development of interval cancer. The development of interval colon cancer is associated with female sex, old age, family history of CRC, comorbidities, diverticulosis, and the skill of the endoscopist. During carcinogenesis, sessile serrated adenomas/polyps (SSA/Ps) share many genomic and colonic site characteristics with I-CRCs. The clinical and biological features of I-CRC should be elucidated to prevent the development of interval colon cancer.

  11. Translational potential of cancer stem cells: A review of the detection of cancer stem cells and their roles in cancer recurrence and cancer treatment. (United States)

    Islam, Farhadul; Gopalan, Vinod; Smith, Robert A; Lam, Alfred K-Y


    Cancer stem cells (CSCs) are a subpopulation of cancer cells with many clinical implications in most cancer types. One important clinical implication of CSCs is their role in cancer metastases, as reflected by their ability to initiate and drive micro and macro-metastases. The other important contributing factor for CSCs in cancer management is their function in causing treatment resistance and recurrence in cancer via their activation of different signalling pathways such as Notch, Wnt/β-catenin, TGF-β, Hedgehog, PI3K/Akt/mTOR and JAK/STAT pathways. Thus, many different therapeutic approaches are being tested for prevention and treatment of cancer recurrence. These may include treatment strategies targeting altered genetic signalling pathways by blocking specific cell surface molecules, altering the cancer microenvironments that nurture cancer stem cells, inducing differentiation of CSCs, immunotherapy based on CSCs associated antigens, exploiting metabolites to kill CSCs, and designing small interfering RNA/DNA molecules that especially target CSCs. Because of the huge potential of these approaches to improve cancer management, it is important to identify and isolate cancer stem cells for precise study and application of prior the research on their role in cancer. Commonly used methodologies for detection and isolation of CSCs include functional, image-based, molecular, cytological sorting and filtration approaches, the use of different surface markers and xenotransplantation. Overall, given their significance in cancer biology, refining the isolation and targeting of CSCs will play an important role in future management of cancer. Copyright © 2015 Elsevier Inc. All rights reserved.

  12. Stem cell dynamics in homeostasis and cancer of the intestine

    NARCIS (Netherlands)

    Vermeulen, Louis; Snippert, Hugo J.


    Intestinal stem cells (ISCs) and colorectal cancer (CRC) biology are tightly linked in many aspects. It is generally thought that ISCs are the cells of origin for a large proportion of CRCs and crucial ISC-associated signalling pathways are often affected in CRCs. Moreover, CRCs are thought to

  13. P97/CDC-48: proteostasis control in tumor cell biology. (United States)

    Fessart, Delphine; Marza, Esther; Taouji, Saïd; Delom, Frédéric; Chevet, Eric


    P97/CDC-48 is a prominent member of a highly evolutionary conserved Walker cassette - containing AAA+ATPases. It has been involved in numerous cellular processes ranging from the control of protein homeostasis to membrane trafficking through the intervention of specific accessory proteins. Expression of p97/CDC-48 in cancers has been correlated with tumor aggressiveness and prognosis, however the precise underlying molecular mechanisms remain to be characterized. Moreover p97/CDC-48 inhibitors were developed and are currently under intense investigation as anticancer drugs. Herein, we discuss the role of p97/CDC-48 in cancer development and its therapeutic potential in tumor cell biology. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  14. In-silico study of small cell lung cancer based on protein structure and function: A new approach to mimic biological system

    Directory of Open Access Journals (Sweden)

    Nidhi Sood


    Full Text Available Lung cancer being the most common disease worldwide that leads to a number of deaths. A huge amount of effort has been done in screening trials for early diagnose treatment which increases the disease-free survival rate. Based on the expression of protein of mouse double minute 2 and tumor protein 53 complex, we have identified the antagonist for this complex that would facilitate the treatment for specific lung cancer. It is a complex disease that involves vast investigation for the characterization of a lung cancer and thus, computational study is being developed to mimic the in vivo system. In this work, a computational process was employed for the identification of these proteins, with a short and simple method to discover protein-protein interactions. Moreover, these proteins have more similarities in their function with the known cancer proteins as compared to those identified from the protein expression specific profiles. A new method that utilizes experimental information to improve the extent of numerical calculations based on free energy profiles from molecular dynamics simulation. The experimental information guides the simulation along relevant pathways and decreases overall computational time. This method introduces umbrella sampling simulations. A new technique umbrella sampling is described where the high efficacy100 of this technique enables uniform sampling with several degrees of freedom. Here, we review the protein interactions techniques and we focus on main concepts in the molecular of in-silico study in lung cancer. This study recruiting new methods proved the efficiency and showed good results.

  15. Intersections of lung progenitor cells, lung disease and lung cancer

    Directory of Open Access Journals (Sweden)

    Carla F. Kim


    Full Text Available The use of stem cell biology approaches to study adult lung progenitor cells and lung cancer has brought a variety of new techniques to the field of lung biology and has elucidated new pathways that may be therapeutic targets in lung cancer. Recent results have begun to identify the ways in which different cell populations interact to regulate progenitor activity, and this has implications for the interventions that are possible in cancer and in a variety of lung diseases. Today's better understanding of the mechanisms that regulate lung progenitor cell self-renewal and differentiation, including understanding how multiple epigenetic factors affect lung injury repair, holds the promise for future better treatments for lung cancer and for optimising the response to therapy in lung cancer. Working between platforms in sophisticated organoid culture techniques, genetically engineered mouse models of injury and cancer, and human cell lines and specimens, lung progenitor cell studies can begin with basic biology, progress to translational research and finally lead to the beginnings of clinical trials.

  16. Cell Biology of the Caenorhabditis elegans Nucleus. (United States)

    Cohen-Fix, Orna; Askjaer, Peter


    Studies on the Caenorhabditis elegans nucleus have provided fascinating insight to the organization and activities of eukaryotic cells. Being the organelle that holds the genetic blueprint of the cell, the nucleus is critical for basically every aspect of cell biology. The stereotypical development of C. elegans from a one cell-stage embryo to a fertile hermaphrodite with 959 somatic nuclei has allowed the identification of mutants with specific alterations in gene expression programs, nuclear morphology, or nuclear positioning. Moreover, the early C. elegans embryo is an excellent model to dissect the mitotic processes of nuclear disassembly and reformation with high spatiotemporal resolution. We review here several features of the C. elegans nucleus, including its composition, structure, and dynamics. We also discuss the spatial organization of chromatin and regulation of gene expression and how this depends on tight control of nucleocytoplasmic transport. Finally, the extensive connections of the nucleus with the cytoskeleton and their implications during development are described. Most processes of the C. elegans nucleus are evolutionarily conserved, highlighting the relevance of this powerful and versatile model organism to human biology. Copyright © 2017 by the Genetics Society of America.

  17. The role of podoplanin in the biology of differentiated thyroid cancers.

    Directory of Open Access Journals (Sweden)

    Magdalena Rudzińska

    Full Text Available Podoplanin (PDPN, a mucin-type transmembrane glycoprotein specific to the lymphatic system is expressed in a variety of human cancers, and is regarded as a factor promoting tumor progression. The purpose of this study was to elucidate the molecular role of PDPN in the biology of thyroid cancer cells. PDPN expression was evaluated in primary thyroid carcinomas and thyroid carcinoma cell lines by RT-qPCR, Western blotting, IF and IHC. To examine the role of podoplanin in determining a cell's malignant potential (cellular migration, invasion, proliferation, adhesion, motility, apoptosis, a thyroid cancer cell line with silenced PDPN expression was used. We observed that PDPN was solely expressed in the cancer cells of 40% of papillary thyroid carcinoma (PTC tissues. Moreover, PDPN mRNA and protein were highly expressed in PTC-derived TPC1 and BcPAP cell lines but were not detected in follicular thyroid cancer derived cell lines. PDPN knock-down significantly decreased cellular invasion, and modestly reduced cell migration, while proliferation and adhesion were not affected. Our results demonstrate that PDPN mediates the invasive properties of cells derived from papillary thyroid carcinomas, suggesting that podoplanin might promote PTC progression.

  18. The characterization of exosomes from biological fluids of patients with different types of cancer (United States)

    Yunusova, N. V.; Tamkovich, S. N.; Stakheeva, M. N.; Grigor'eva, A. A.; Somov, A. K.; Tugutova, E. A.; Kolomiets, L. A.; Molchanov, S. V.; Afanas'ev, S. G.; Kakurina, G. V.; Choinzonov, E. L.; Kondakova, I. V.


    Exosomes are extracellular membrane structures involved in many physiological and pathological processes including cancerogenesis and metastasis. The purpose of the study was to isolate, identify and analyze the total content of exosomes in biological fluids. The exosomes from the plasma and ascites samples of the patients with ovarian cancer, from the blood plasma of the patients with colorectal and head and neck squamous cell cancer as well as from the blood plasma of healthy donors were characterized using transmission electron microscopy and flow cytometry. The subpopulations of the exosomes in the biological fluids of the patients with different types of cancer were similar, but the protein concentrations of exosomes were different. In this paper we present the methodological approaches allowing us to obtain high quality exosome preparations from biological fluids.

  19. Cell-free synthetic biology: Engineering in an open world


    Lu, Yuan


    Cell-free synthetic biology emerges as a powerful and flexible enabling technology that can engineer biological parts and systems for life science applications without using living cells. It provides simpler and faster engineering solutions with an unprecedented freedom of design in an open environment than cell system. This review focuses on recent developments of cell-free synthetic biology on biological engineering fields at molecular and cellular levels, including protein engineering, met...

  20. Urinary bladder cancer in dogs, a naturally occurring model for cancer biology and drug development. (United States)

    Knapp, Deborah W; Ramos-Vara, José A; Moore, George E; Dhawan, Deepika; Bonney, Patty L; Young, Kirsten E


    Each year more than 65,000 people are diagnosed with urinary bladder cancer, and more than 14,000 people die from the disease in the United States. Studies in relevant animal models are essential to improve the management of bladder cancer. Naturally occurring bladder cancer in dogs very closely mimics human invasive bladder cancer, specifically high-grade invasive transitional cell carcinoma (TCC; also referred to as invasive urothelial carcinoma) in cellular and molecular features; biological behavior, including sites and frequency of metastasis; and response to therapy. Canine bladder cancer complements experimentally induced rodent tumors in regard to animal models of bladder cancer. Results of cellular and molecular studies and -omics analyses in dogs are expected to lead to improved detection of TCC and preneoplastic lesions, earlier intervention, better prediction of patient outcome, and more effective TCC management overall. Studies in dogs are being used to help define heritable risks (through very strong breed-associated risk) and environment risks and to evaluate prevention and treatment approaches that benefit humans as well as dogs. Clinical treatment trials in pet dogs with TCC are considered a win-win scenario by clinician scientists and pet owners. The individual dog benefits from effective treatment, the results are expected to help other dogs, and the findings are expected to ultimately help humans with TCC. This article provides an overview of canine TCC, a summary of the similarities and differences between canine and human invasive TCC, and examples of the types of valuable translational research that can be done using dogs with naturally occurring TCC. © The Author 2014. Published by Oxford University Press on behalf of the Institute for Laboratory Animal Research. All rights reserved. For permissions, please email:

  1. AACR Centennial Series: The Biology of Cancer Metastasis: Historical Perspective (United States)

    Talmadge, James E; Fidler, Isaiah J


    Metastases resistant to therapy is the major cause of death from cancer. Despite almost 200 years of study, the process of tumor metastasis remains controversial. Stephen Paget initially identified the role of host-tumor interactions on the basis of a review of autopsy records. His “seed and soil” hypothesis was substantiated a century later with experimental studies and numerous reports have confirmed these seminal observations. Inarguably, an improved understanding of the metastatic process and the attributes of the cells selected by this process are critical to the treatment of patients with systemic disease. In many patients, metastasis has occurred by the time of diagnosis, such that metastasis prevention may not be relevant, and treatment of systemic disease, as well as the identity of patients with early disease, should be our goal. During the last three decades, revitalized research has focused on new discoveries in the biology of metastasis. While our understanding of the molecular events that regulate metastasis has improved; nonetheless, the relevant contributions and timing of molecular lesion(s) potentially involved in its pathogenesis remain unclear. The history of pioneering observations and discussion of current controversies should help investigators understand the complex and multifactorial interactions between the host and selected tumor cells that contribute to fatal metastasis and allow for the design of successful therapy. PMID:20610625

  2. Systems biology for organotypic cell cultures. (United States)

    Grego, Sonia; Dougherty, Edward R; Alexander, Francis J; Auerbach, Scott S; Berridge, Brian R; Bittner, Michael L; Casey, Warren; Cooley, Philip C; Dash, Ajit; Ferguson, Stephen S; Fennell, Timothy R; Hawkins, Brian T; Hickey, Anthony J; Kleensang, Andre; Liebman, Michael N J; Martin, Florian; Maull, Elizabeth A; Paragas, Jason; Qiao, Guilin Gary; Ramaiahgari, Sreenivasa; Sumner, Susan J; Yoon, Miyoung


    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.

  3. 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)


    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.

  4. Three-dimensional tissue culture models in cancer biology. (United States)

    Kim, Jong Bin


    Three-dimensional (3D) tissue culture models have an invaluable role in tumour biology today providing some very important insights into cancer biology. As well as increasing our understanding of homeostasis, cellular differentiation and tissue organization they provide a well defined environment for cancer research in contrast to the complex host environment of an in vivo model. Due to their enormous potential 3D tumour cultures are currently being exploited by many branches of biomedical science with therapeutically orientated studies becoming the major focus of research. Recent advances in 3D culture and tissue engineering techniques have enabled the development of more complex heterologous 3D tumour models.

  5. Stromal cells in tumor microenvironment and breast cancer. (United States)

    Mao, Yan; Keller, Evan T; Garfield, David H; Shen, Kunwei; Wang, Jianhua


    Cancer is a systemic disease encompassing multiple components of both tumor cells themselves and host stromal cells. It is now clear that stromal cells in the tumor microenvironment play an important role in cancer development. Molecular events through which reactive stromal cells affect cancer cells can be defined so that biomarkers and therapeutic targets can be identified. Cancer-associated fibroblasts (CAFs) make up the bulk of cancer stroma and affect the tumor microenvironment such that they promote cancer initiation, angiogenesis, invasion, and metastasis. In breast cancer, CAFs not only promote tumor progression but also induce therapeutic resistance. Accordingly, targeting CAFs provides a novel way to control tumors with therapeutic resistance. This review summarizes the current understandings of tumor stroma in breast cancer with a particular emphasis on the role of CAFs and the therapeutic implications of CAFs. In addition, the effects of other stromal components such as endothelial cells, macrophages, and adipocytes in breast cancer are also discussed. Finally, we describe the biologic markers to categorize patients into a specific and confirmed subtype for personalized treatment.

  6. Stroma Cells in Tumor Microenvironment and Breast Cancer (United States)

    Mao, Yan; Keller, Evan T.; Garfield, David H.; Shen, Kunwei; Wang, Jianhua


    Cancer is a systemic disease, encompassing multiple components of both tumor cells themselves and host stromal cells. It is now clear that stromal cells in the tumor microenvironment play an important role in cancer development. Molecular events through which reactive stromal cells affect cancer cells can be defined so that biomarkers and therapeutic targets can be identified. Cancer-associated fibroblasts (CAFs) make up the bulk of cancer stroma and affect the tumor microenvironment such that they promote cancer initiation, angiogenesis, invasion and metastasis. In breast cancer, CAFs not only promote tumor progression, but also induce therapeutic resistances. Accordingly, targeting CAFs provides a novel way to control tumors with therapeutic resistances. This review summarizes the current understanding of tumor stroma in breast cancer with a particular emphasis on the role of CAFs and the therapeutic implications of CAFs. The effects of other stromal components such as endothelial cells, macrophages and adipocytes in breast cancer are also discussed. Finally, we describe the biologic markers to sort patients into a specific and confirmed subtype for personalized treatment. PMID:23114846

  7. Chemical inhibition of fatty acid synthase: molecular docking analysis and biochemical validation in ocular cancer cells

    National Research Council Canada - National Science Library

    Deepa, P R; Vandhana, S; Muthukumaran, S; Umashankar, V; Jayanthi, U; Krishnakumar, S


    ...: cerulenin, triclosan and orlistat. The IC50 and dose-dependent sensitivity of cancer cells to FASN inhibitors decrease in biologic enzyme activity, and cell morphology alterations were analysed...

  8. Do Cell Phones Cause Cancer?

    CERN Document Server

    Leikind, Bernard


    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...

  9. Cell Biology Apps for Apple Devices


    Stark, Louisa A.


    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,...

  10. Light sheet microscopy in cell biology. (United States)

    Tomer, Raju; Khairy, Khaled; Keller, Philipp J


    Light sheet-based fluorescence microscopy (LSFM) is emerging as a powerful imaging technique for the life sciences. LSFM provides an exceptionally high imaging speed, high signal-to-noise ratio, low level of photo-bleaching, and good optical penetration depth. This unique combination of capabilities makes light sheet-based microscopes highly suitable for live imaging applications. Here, we provide an overview of light sheet-based microscopy assays for in vitro and in vivo imaging of biological samples, including cell extracts, soft gels, and large multicellular organisms. We furthermore describe computational tools for basic image processing and data inspection.

  11. Cell biology and EMF safety standards. (United States)

    Blank, Martin


    Living cells react defensively and start to synthesize stress proteins when exposed to potentially harmful stimuli. Electromagnetic fields (EMF) are among the many different environmental stimuli that initiate stress protein synthesis. Although there is greater energy transfer and heating due to EMF at higher frequencies, there is no greater stress response. The cellular stress response is far more sensitive to EMF than to an increase in temperature. It should be obvious that an EMF safety standard should be based on the more sensitive, natural biological response.

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

    NARCIS (Netherlands)

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


    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

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

    Directory of Open Access Journals (Sweden)

    Melville DOS


    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.

  14. CellNet: network biology applied to stem cell engineering. (United States)

    Cahan, Patrick; Li, Hu; Morris, Samantha A; Lummertz da Rocha, Edroaldo; Daley, George Q; Collins, James J


    Somatic cell reprogramming, directed differentiation of pluripotent stem cells, and direct conversions between differentiated cell lineages represent powerful approaches to engineer cells for research and regenerative medicine. We have developed CellNet, a network biology platform that more accurately assesses the fidelity of cellular engineering than existing methodologies and generates hypotheses for improving cell derivations. Analyzing expression data from 56 published reports, we found that cells derived via directed differentiation more closely resemble their in vivo counterparts than products of direct conversion, as reflected by the establishment of target cell-type gene regulatory networks (GRNs). Furthermore, we discovered that directly converted cells fail to adequately silence expression programs of the starting population and that the establishment of unintended GRNs is common to virtually every cellular engineering paradigm. CellNet provides a platform for quantifying how closely engineered cell populations resemble their target cell type and a rational strategy to guide enhanced cellular engineering. Copyright © 2014 Elsevier Inc. All rights reserved.

  15. Biological Basis for Chemoprevention of Ovarian Cancer (United States)


    During the study interview a thorough history of the menstrual cycle and reproductive experiences of the study participants is obtained from each...cancer.24 The scope of vitamin D deficiency extends well beyond the elderly however, as widespread vitamin D deficiency is common in adolescents and...gene in ras-transformed keratinocytes demonstrates that locally produced 1alpha,25-dihydroxyvitamin D3 suppresses growth and induces differentiation in

  16. The biology of male breast cancer. (United States)

    Fentiman, Ian S


    Important differences have begun to emerge concerning the molecular profile of female and male breast cancer which may prove to be of therapeutic value. This review examined all the available data on the genomics of MBC. Most male cancers are ER+ve but without a corresponding increase in PR positivity and only a weaker association with estrogen-controlled markers such as PS2, HSP27 and Cathepsin-D. HER2 +ve cancers are rare in males and the role of androgen receptor is controversial. Although the Luminal A phenotype was the most frequent in both MBC and FBC, no Luminal B or HER2 phenotypes were found in males and the basal phenotype was very rare. Using hierarchical clustering in FBC, ERα clustered with PR, whereas in MBC, ERα associated with ERβ and AR. Based on limited data it appears that Oncotype DX is effective in determining recurrence risk in selected MBC. In future, tailored therapies based on genomics will probably yield the most promising approach for both MBC and FBC. Copyright © 2018 Elsevier Ltd. All rights reserved.

  17. Femtosecond diffractive imaging of biological cells

    Energy Technology Data Exchange (ETDEWEB)

    Marvin Seibert, M; Boutet, Sebastien; Svenda, Martin; Ekeberg, Tomas; Maia, Filipe R N C; TImneanu, Nicusor; Caleman, Carl; Hajdu, Janos [Laboratory of Molecular Biophysics, Department of Cell and Molecular Biology, Uppsala University, Husargatan 3, Box 596, SE-75124 Uppsala (Sweden); Bogan, Michael J [SLAC National Accelerator Laboratory, 2575 Sand Hill Road, Menlo Park, CA 94025 (United States); Barty, Anton; Hau-Riege, Stefan; Frank, Matthias; Benner, Henry [Lawrence Livermore National Laboratory, 7000 East Avenue, Livermore, CA 94550 (United States); Lee, Joanna Y [Department of Biology, Stanford University, Stanford, CA 94305 (United States); Marchesini, Stefano [Advanced Light Source, Lawrence Berkeley National Laboratory, Berkeley, CA 94720 (United States); Shaevitz, Joshua W [150 Carl Icahn Laboratory, Princeton University, Princeton, NJ 08544 (United States); Fletcher, Daniel A [Bioengineering and Biophysics, University of California, Berkeley, CA 94720 (United States); Bajt, Sasa [Photon Science, DESY, Notkestrasse 85, 22607 Hamburg (Germany); Andersson, Inger [Department of Molecular Biology, Swedish University of Agricultural Sciences, Husargatan 3, Box 590, SE-751 24 Uppsala (Sweden); Chapman, Henry N, E-mail: marvin@xray.bmc.uu.s, E-mail: janos@xray.bmc.uu.s [Center for Free-Electron Laser Science, University of Hamburg and DESY, Notkestrasse 85, Hamburg (Germany)


    In a flash diffraction experiment, a short and extremely intense x-ray pulse illuminates the sample to obtain a diffraction pattern before the onset of significant radiation damage. The over-sampled diffraction pattern permits phase retrieval by iterative phasing methods. Flash diffractive imaging was first demonstrated on an inorganic test object (Chapman et al 2006 Nat. Phys. 2 839-43). We report here experiments on biological systems where individual cells were imaged, using single, 10-15 fs soft x-ray pulses at 13.5 nm wavelength from the FLASH free-electron laser in Hamburg. Simulations show that the pulse heated the sample to about 160 000 K but not before an interpretable diffraction pattern could be obtained. The reconstructed projection images return the structures of the intact cells. The simulations suggest that the average displacement of ions and atoms in the hottest surface layers remained below 3 A during the pulse.

  18. Cell Biology of the Plant Nucleus. (United States)

    Meier, Iris; Richards, Eric J; Evans, David E


    The eukaryotic nucleus is enclosed by the nuclear envelope, which is perforated by the nuclear pores, the gateways of macromolecular exchange between the nucleoplasm and cytoplasm. The nucleoplasm is organized in a complex three-dimensional fashion that changes over time and in response to stimuli. Within the cell, the nucleus must be viewed as an organelle (albeit a gigantic one) that is a recipient of cytoplasmic forces and capable of morphological and positional dynamics. The most dramatic reorganization of this organelle occurs during mitosis and meiosis. Although many of these aspects are less well understood for the nuclei of plants than for those of animals or fungi, several recent discoveries have begun to place our understanding of plant nuclei firmly into this broader cell-biological context.

  19. Can molecular cell biology explain chromosome motions?

    Directory of Open Access Journals (Sweden)

    Gagliardi L


    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.

  20. Can molecular cell biology explain chromosome motions? (United States)

    Shain, Daniel H; Gagliardi, L John


    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. 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. 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. © 2011 Shain and Gagliardi; licensee BioMed Central Ltd.

  1. Renal cell cancer among African Americans: an epidemiologic review (United States)


    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. PMID:21486465

  2. Neuroblastoma: Developmental Biology, Cancer Genomics, and Immunotherapy (United States)

    Cheung, Nai-Kong V.; Dyer, Michael A.


    Neuroblastoma is a solid tumor that arises from the developing sympathetic nervous system. Over the past decade, our understanding of this disease has advanced tremendously. The future challenge is to apply the knowledge gained toward developing risk-based therapies and ultimately improving outcome. Here we review the key discoveries in the developmental biology, molecular genetics, and immunology of neuroblastoma, as well as new translational tools to bring these promising scientific advances into the clinic. PMID:23702928

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

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


    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.

  4. 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: [Developmental Biology Laboratory, Hopital Maisonneuve-Rosemont, 5415 Boul. l' Assomption, Montreal, H1T 2M4 (Canada); Faculté de Médecine, Université de Montréal, Montréal, H3T 1J4 (Canada)


    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.

  5. Cell wall biology: perspectives from cell wall imaging. (United States)

    Lee, Kieran J D; Marcus, Susan E; Knox, J Paul


    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.

  6. Breast cancer circulating tumor cells

    Directory of Open Access Journals (Sweden)

    Maria Joao Carvalho


    Full Text Available Metastasization of breast cancer involves various mechanisms responsible for progression from invasive lesion to dissemination in distant organs. Regional lymph node metastasization was considered an initial step in this process, but it is now recognized that hematogenous dissemination is a deviation from lymphatic circulation. The detection of circulating tumor cells (CTC is an aim in several oncology areas. For this purpose, several techniques have been used to detect CTC, including the use of antibodies and techniques with nucleic acids. This study reviews the published studies considering the detection of breast cancer CTC. There are focused the difficulties in identifying a CTC in a heterogeneous population, the handling of the sample, criteria of positivity, analytical techniques, and specific markers. There are systematized various specific markers of breast cancer cells also the problems with false positive results. Finally, we hypothesize clinical applications either as a prognostic marker or as a therapeutic response monitor.

  7. Molecular biology of normal melanocytes and melanoma cells. (United States)

    Bandarchi, Bizhan; Jabbari, Cyrus Aleksandre; Vedadi, Ali; Navab, Roya


    Malignant melanoma is one of the most aggressive malignancies in humans and is responsible for 60-80% of deaths from skin cancers. The 5-year survival of patients with metastatic malignant melanoma is about 14%. Its incidence has been increasing in the white population over the past two decades. The mechanisms leading to malignant transformation of melanocytes and melanocytic lesions are poorly understood. In developing malignant melanoma, there is a complex interaction of environmental and endogenous (genetic) factors, including: dysregulation of cell proliferation, programmed cell death (apoptosis) and cell-to-cell interactions. The understanding of genetic alterations in signalling pathways of primary and metastatic malignant melanoma and their interactions may lead to therapeutics modalities, including targeted therapies, particularly in advanced melanomas that have high mortality rates and are often resistant to chemotherapy and radiotherapy. Our knowledge regarding the molecular biology of malignant melanoma has been expanding. Even though several genes involved in melanocyte development may also be associated with melanoma cell development, it is still unclear how a normal melanocyte becomes a melanoma cell. This article reviews the molecular events and recent findings associated with malignant melanoma.

  8. Colorectal Cancer Stem Cells and Cell Death

    Energy Technology Data Exchange (ETDEWEB)

    Catalano, Veronica [Department of Surgical and Oncological Sciences, University of Palermo, Via Liborio Giuffrè 5, 90127 Palermo, PA (Italy); Gaggianesi, Miriam [Department of Surgical and Oncological Sciences, University of Palermo, Via Liborio Giuffrè 5, 90127 Palermo, PA (Italy); Department of Cellular and Molecular Oncology, IRCCS Fondazione Salvatore Maugeri, Via Salvatore Maugeri, 27100 Pavia, PV (Italy); Spina, Valentina; Iovino, Flora [Department of Surgical and Oncological Sciences, University of Palermo, Via Liborio Giuffrè 5, 90127 Palermo, PA (Italy); Dieli, Francesco [Departement of Biopathology and Medicine Biotechnologies, University of Palermo, Via Liborio Giuffrè 5, 90127 Palermo, PA (Italy); Stassi, Giorgio, E-mail: [Department of Surgical and Oncological Sciences, University of Palermo, Via Liborio Giuffrè 5, 90127 Palermo, PA (Italy); Department of Cellular and Molecular Oncology, IRCCS Fondazione Salvatore Maugeri, Via Salvatore Maugeri, 27100 Pavia, PV (Italy); Todaro, Matilde [Department of Surgical and Oncological Sciences, University of Palermo, Via Liborio Giuffrè 5, 90127 Palermo, PA (Italy)


    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.

  9. Isolation and characterization of spheroid cells from the HT29 colon cancer cell line. (United States)

    Fan, Xinlan; Ouyang, Nengyong; Teng, Hong; Yao, Herui


    Colorectal cancer stem cells (Cr-CSCs) are involved in the growth of colon cancer, but their specific role in tumor biology, including metastasis, is still unclear. Currently, methods for sorting Cr-CSCs are based on the expression of surface markers (e.g., CD133(+), CD44(+), and aldehyde dehydrogenase 1 (ALDH1(+))); however, the specificity of these markers for Cr-CSCs is uncertain. This study aimed to develop more effective ways of isolating and purifying Cr-CSCs. Suspension culture was used for isolation of Cr-CSCs. And spheroid cells were performed by side population technology, and the putative molecular marker analysis of colorectal cancer stem cell. Migration assay and chemoresistance experiment were conducted between the adherent cells and spheroid cells. HT29 colon cancer cells grew well in suspension culture. The percentage of CD44(+) cancer cell of spheroid cells was 68 times higher than that of adherent cells (89.5% vs. 1.3%), but there was no obvious difference in the percentage of CD133(+) cells (6.25% vs. 5.6%). Moreover, it is worth noting that the percent of CD133 (+)/CD44(+) cells remarkably rose (from 0.6% to 5.4%). The expression of ALDH1 was markedly increased (7.5% vs. 20.5%) for the spheroid cells than the adherent cells. The side population within the spheroid population dramatically increased from 0.2% to 6.3%. The resistance of spheroid cells to 5-FU was higher than that of adherent cells, as was their ability to migrate in the presence of SDF-1α. Suspension culture is an effective approach for enriching Cr-CSCs and can provide an inexhaustible supply of genetically stable colon cancer stem cells for targeted Cr-CSC studies. Spheroid cell models also enable the study of colon cancer chemoresistance and metastasis and may help to elucidate the role of cancer stem cells in colon cancer.

  10. Pleiotropic effects of cancer cells' secreted factors on human stromal (mesenchymal) stem cells

    DEFF Research Database (Denmark)

    Al-toub, Mashael; Almusa, Abdulaziz; Almajed, Mohammed


    cells' secreted factors as represented by a panel of human cancer cell lines (breast (MCF7 and MDA-MB-231); prostate (PC-3); lung (NCI-H522); colon (HT-29) and head & neck (FaDu)) on the biological characteristics of MSCs. METHODS: Morphological changes were assessed using fluorescence microscopy......, but not from MCF7 and HT-29, developed an elongated, spindle-shaped morphology with bipolar processes. In association with phenotypic changes, genome-wide gene expression and bioinformatics analysis revealed an enhanced pro-inflammatory response of those MSCs. Pharmacological inhibitions of FAK and MAPKK......INTRODUCTION: Studying cancer tumors' microenvironment may reveal a novel role in driving cancer progression and metastasis. The biological interaction between stromal (mesenchymal) stem cells (MSCs) and cancer cells remains incompletely understood. Herein, we investigated the effects of tumor...

  11. Gene Delivery for Metastatic Prostate Cancer Cells

    National Research Council Canada - National Science Library

    Pang, Shen


    .... Enhanced by the bystander effect, the specific expression of the DTA gene causes significant cell death in prostate cancer cell cultures, with very low background cell eradication in control cell lines...

  12. Stem cells in prostate cancer. (United States)

    Mateo, Francesca; Fernandez, Pedro L; Thomson, Timothy M


    Tumors constitute complex ecosystems with multiple interactions among neoplastic cells displaying various phenotypes and functions and where the tumoral niche is built with an active participation of the host environment that also impacts the malignant progression of the tumor cells. Irrespective of the cell of origin of prostate adenocarcinoma, mounting evidences support the existence of a hierarchy within neoplastic prostate cells that contributes to the heterogeneity of these tumors. At the origin of this hierarchy are small populations of tumor cells with high self-renewal potential and also capable of generating progeny tumor cells that lose self-renewal properties as they acquire more differentiated phenotypes. These cancer stem cells (CSC) depend on active gene networks that confer them with their self-renewal capacity through symmetrical divisions whereas they can also undergo asymmetrical division and differentiation either as stochastic events or in response to environmental cues. Although new experimental evidences indicate that this is can be a reversible process, thus blurring the distinction between CSCs and non-CSCs, the former are considered as the drivers of tumor growth and evolution, and thus a prime target for therapeutic intervention. Of particular importance in prostate cancer, CSCs may constitute the repository population of androgen-insensitive and chemotherapy-resistant tumor cells responsible for castration-resistant and chemotherapy-insensitive tumors, thus their identification and quantification in primary and metastatic neoplasms could play important roles in the management of this disease.

  13. Surgery for nonsmall cell lung cancer

    Directory of Open Access Journals (Sweden)

    Loïc Lang-Lazdunski


    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.

  14. Fungus-mediated biological synthesis of gold nanoparticles: potential in detection of liver cancer (United States)

    Chauhan, Arun; Zubair, Swaleha; Tufail, Saba; Sherwani, Asif; Sajid, Mohammad; Raman, Suri C; Azam, Amir; Owais, Mohammad


    Background Nanomaterials are considered to be the pre-eminent component of the rapidly advancing field of nanotechnology. However, developments in the biologically inspired synthesis of nanoparticles are still in their infancy and consequently attracting the attention of material scientists throughout the world. Keeping in mind the fact that microorganism-assisted synthesis of nanoparticles is a safe and economically viable prospect, in the current study we report Candida albicans-mediated biological synthesis of gold nanoparticles. Methods and results Transmission electron microscopy, atomic force microscopy, and various spectrophotometric analyses were performed to characterize the gold nanoparticles. The morphology of the synthesized gold particles depended on the abundance of C. albicans cytosolic extract. Transmission electron microscopy, nanophox particle analysis, and atomic force microscopy revealed the size of spherical gold nanoparticles to be in the range of 20–40 nm and nonspherical gold particles were found to be 60–80 nm. We also evaluated the potential of biogenic gold nanoparticles to probe liver cancer cells by conjugating them with liver cancer cell surface-specific antibodies. The antibody-conjugated gold particles were found to bind specifically to the surface antigens of the cancer cells. Conclusion The antibody-conjugated gold particles synthesized in this study could successfully differentiate normal cell populations from cancerous cells. PMID:22072868

  15. Roles of pH and the Na+/H+ exchanger NHE1 in cancer: From cell biology and animal models to an emerging translational perspective? (United States)

    Stock, Christian; Pedersen, Stine Falsig


    Acidosis is characteristic of the solid tumor microenvironment. Tumor cells, because they are highly proliferative and anabolic, have greatly elevated metabolic acid production. To sustain a normal cytosolic pH homeostasis they therefore need to either extrude excess protons or to neutralize them by importing HCO3-, in both cases causing extracellular acidification in the poorly perfused tissue microenvironment. The Na+/H+ exchanger isoform 1 (NHE1) is a ubiquitously expressed acid-extruding membrane transport protein, and upregulation of its expression and/or activity is commonly correlated with tumor malignancy. The present review discusses current evidence on how altered pH homeostasis, and in particular NHE1, contributes to tumor cell motility, invasion, proliferation, and growth and facilitates evasion of chemotherapeutic cell death. We summarize data from in vitro studies, 2D-, 3D- and organotypic cell culture, animal models and human tissue, which collectively point to pH-regulation in general, and NHE1 in particular, as potential targets in combination chemotherapy. Finally, we discuss the possible pitfalls, side effects and cellular escape mechanisms that need to be considered in the process of translating the plethora of basic research data into a clinical setting. Copyright © 2016 Elsevier Ltd. All rights reserved.

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

    NARCIS (Netherlands)

    Pore, M.M.; Meijer, C.; de Bock, G.H.; Boersma-van Ek, W.; Terstappen, Leonardus Wendelinus Mathias Marie; Groen, H.J.M.; Timens, W.; Kruyt, F.A.E.; Hiltermann, T.N.J.


    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

  17. RNA Systems Biology for Cancer: From Diagnosis to Therapy. (United States)

    Amirkhah, Raheleh; Farazmand, Ali; Wolkenhauer, Olaf; Schmitz, Ulf


    It is due to the advances in high-throughput omics data generation that RNA species have re-entered the focus of biomedical research. International collaborate efforts, like the ENCODE and GENCODE projects, have spawned thousands of previously unknown functional non-coding RNAs (ncRNAs) with various but primarily regulatory roles. Many of these are linked to the emergence and progression of human diseases. In particular, interdisciplinary studies integrating bioinformatics, systems biology, and biotechnological approaches have successfully characterized the role of ncRNAs in different human cancers. These efforts led to the identification of a new tool-kit for cancer diagnosis, monitoring, and treatment, which is now starting to enter and impact on clinical practice. This chapter is to elaborate on the state of the art in RNA systems biology, including a review and perspective on clinical applications toward an integrative RNA systems medicine approach. The focus is on the role of ncRNAs in cancer.

  18. 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: [Department of Physiology, Faculty of Medicine and Odontology, University of Valencia, 17 Av. Blasco Ibanez, 46010 Valencia (Spain)


    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.

  19. Breast Cancer Biology: Clinical Implications for Breast Radiation Therapy. (United States)

    Horton, Janet K; Jagsi, Reshma; Woodward, Wendy A; Ho, Alice


    Historically, prognosis and treatment decision making for breast cancer patients have been dictated by the anatomic extent of tumor spread. However, in recent years, "breast cancer" has proven to be a collection of unique phenotypes with distinct prognoses, patterns of failure, and treatment responses. Recent advances in biologically based assays and targeted therapies designed to exploit these unique phenotypes have profoundly altered systemic therapy practice patterns and treatment outcomes. Data associating locoregional outcomes with tumor biology are emerging. However, the likelihood of obtaining level I evidence for fundamental radiation therapy questions within each of the specific subtypes in the immediate future is low. As such, this review aims to summarize the existing data and provide practical context for the incorporation of breast tumor biology into clinical practice. Copyright © 2017 Elsevier Inc. All rights reserved.

  20. Seeing Cells: Teaching the Visual/Verbal Rhetoric of Biology (United States)

    Dinolfo, John; Heifferon, Barbara; Temesvari, Lesly A.


    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…

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

    Directory of Open Access Journals (Sweden)

    Tiantian Liu


    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.

  2. Isolation and identification of a distinct side population cancer cells in the human epidermal squamous cancer cell line A431. (United States)

    Geng, Songmei; Wang, Qianqian; Wang, Jianli; Hu, Zhishang; Liu, Chunchun; Qiu, Junkang; Zeng, Weihui


    Side population (SP) cells have been suggested to be multipotent cancer stem cells. To address whether SP cells exist in epidermal squamous cancer cell line A431, A431 cells dyed with Hoechst 33342 were sorted through flow cytometry. The SP cells were then analyzed by colony-forming and cell proliferation assay. Further, tumorigenicity and microarray analysis were used to compare biological difference between SP and non-SP (NSP) cells. Our results showed that SP cells existed in the A431 cell line, showing higher proliferating and colony-forming ability than NSP cells. Tumors generated from SP cells were larger than those from the NSP cells in NOD/SCID mice. The mRNA microarray profiling revealed that five cancer marker gene expressions were up-regulated and one tumor suppressor gene expression was down-regulated. These findings suggest that SP cells in A431 could contribute to self-renewal, neoplastic transformation, and cancer metastasis of human epidermal squamous cell carcinoma.

  3. [Dendritic cells in cancer immunotherapy]. (United States)

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


    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.

  4. Exosomes derived from gastric cancer cells activate NF-κB pathway in macrophages to promote cancer progression. (United States)

    Wu, Lijun; Zhang, Xu; Zhang, Bin; Shi, Hui; Yuan, Xiao; Sun, Yaoxiang; Pan, Zhaoji; Qian, Hui; Xu, Wenrong


    Exosomes are nano-sized membrane vesicles secreted by both normal and cancer cells. Emerging evidence indicates that cancer cells derived exosomes contribute to cancer progression through the modulation of tumor microenvironment. However, the effects of exosomes derived from gastric cancer cells on macrophages are not well understood. In this study, we investigated the biological role of gastric cancer cells derived exosomes in the activation of macrophages. We demonstrated that gastric cancer cells derived exosomes activated macrophages to express increased levels of proinflammatory factors, which in turn promoted tumor cell proliferation and migration. In addition, gastric cancer cells derived exosomes remarkably upregulated the phosphorylation of NF-κB in macrophages. Inhibiting the activation of NF-κB reversed the upregulation of proinflammatory factors in macrophages and blocked their promoting effects on gastric cancer cells. Moreover, we found that gastric cancer cells derived exosomes could also activate macrophages from human peripheral blood monocytes through the activation of NF-κB. In conclusion, our results suggest that gastric cancer cells derived exosomes stimulate the activation of NF-κB pathway in macrophages to promote cancer progression, which provides a potential therapeutic approach for gastric cancer by interfering with the interaction between exosomes and macrophages in tumor microenvironment.

  5. Proteasome expression and activity in cancer and cancer stem cells. (United States)

    Voutsadakis, Ioannis A


    Proteasome is a multi-protein organelle that participates in cellular proteostasis by destroying damaged or short-lived proteins in an organized manner guided by the ubiquitination signal. By being in a central place in the cellular protein complement homeostasis, proteasome is involved in virtually all cell processes including decisions on cell survival or death, cell cycle, and differentiation. These processes are important also in cancer, and thus, the proteasome is an important regulator of carcinogenesis. Cancers include a variety of cells which, according to the cancer stem cell theory, descend from a small percentage of cancer stem cells, alternatively termed tumor-initiating cells. These cells constitute the subsets that have the ability to propagate the whole variety of cancer and repopulate tumors after cytostatic therapies. Proteasome plays a role in cellular processes in cancer stem cells, but it has been found to have a decreased function in them compared to the rest of cancer cells. This article will discuss the transcriptional regulation of proteasome sub-unit proteins in cancer and in particular cancer stem cells and the relationship of the proteasome with the pluripotency that is the defining characteristic of stem cells. Therapeutic opportunities that present from the understanding of the proteasome role will also be discussed.

  6. Mathematical and Statistical Modeling in Cancer Systems Biology

    Directory of Open Access Journals (Sweden)

    Rachael eHageman Blair


    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.

  7. A unifying biology of sex steroid-induced apoptosis in prostate and breast cancers (United States)

    Abderrahman, Balkees; Curpan, Ramona F; Hawsawi, Yousef M; Fan, Ping; Jordan, V Craig


    Prostate and breast cancer are the two cancers with the highest incidence in men and women, respectively. Here, we focus on the known biology of acquired resistance to antihormone therapy of prostate and breast cancer and compare laboratory and clinical similarities in the evolution of the disease. Laboratory studies and clinical observations in prostate and breast cancer demonstrate that cell selection pathways occur during acquired resistance to antihormonal therapy. Following sex steroid deprivation, both prostate and breast cancer models show an initial increased acquired sensitivity to the growth potential of sex steroids. Subsequently, prostate and breast cancer cells either become dependent upon the antihormone treatment or grow spontaneously in the absence of hormones. Paradoxically, the physiologic sex steroids now kill a proportion of selected, but vulnerable, resistant tumor cells. The sex steroid receptor complex triggers apoptosis. We draw parallels between acquired resistance in prostate and breast cancer to sex steroid deprivation. Clinical observations and patient trials confirm the veracity of the laboratory studies. We consider therapeutic strategies to increase response rates in clinical trials of metastatic disease that can subsequently be applied as a preemptive salvage adjuvant therapy. The goal of future advances is to enhance response rates and deploy a safe strategy earlier in the treatment plan to save lives. The introduction of a simple evidence-based enhanced adjuvant therapy as a global healthcare strategy has the potential to control recurrence, reduce hospitalization, reduce healthcare costs and maintain a healthier population that contributes to society. PMID:29162647

  8. Prostate Cancer Stem Cells: Research Advances

    Directory of Open Access Journals (Sweden)

    Dagmara Jaworska


    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.

  9. Squamous Cell Lung Cancer: From Tumor Genomics to Cancer Therapeutics (United States)

    Gandara, David R.; Hammerman, Peter S.; Sos, Martin L.; Lara, Primo N.; Hirsch, Fred R.


    Squamous cell lung cancer (SCC) represents an area of unmet need in lung cancer research. For the last several years, therapeutic progress in SCC has lagged behind the now more common NSCLC histologic subtype of adenocarcinoma. However, recent efforts to define the complex biology underlying SCC have begun to bear fruit in a multitude of ways, including characterization of previously unknown genomic and signaling pathways, delineation of new potentially actionable molecular targets, and subsequent development of a large number of agents directed against unique SCC-associated molecular abnormalities. For the first time, SCC-specific prognostic gene signatures and predictive biomarkers of new therapeutic agents are emerging. In addition, recent and ongoing clinical trials, including the Lung-MAP master protocol, have been designed to facilitate approval of targeted therapy-biomarker combinations. In this comprehensive review we describe the current status of SCC therapeutics, recent advances in the understanding of SCC biology and prognostic gene signatures, and the development of innovative new clinical trials, all of which offer new hope for patients with advanced SCC. PMID:25979930

  10. A preliminary study of side population cells in human gastric cancer cell line HGC-27. (United States)

    Gao, Ganglong; Sun, Zhenliang; Wenyong, Liu; Dongxia, Ye; Zhao, Runjia; Zhang, Xueli


    Cancer stem cell-like side population (SP) cells, which may be responsible for recurrence, tumor metastasis, and resistance to cancer therapy, have been identified and characterized in several types of cell lines from gastric cancer. However, there is no report on isolation of SP cells from human gastric cancer cell line HGC-27. This study aims to analyze the proportion of SP cells in HGC-27 cell line, differentiate SP from non-side population (NSP) cells, and determine whether the SP cells have certain biological properties of stem cells. (1) HGC-27 suspension was prepared and stained with Hoechst33342 and PI for flow cytometric isolation of SP (2). Differences in proliferation and stemness-related gene expression profiles (CD133, CD44, OCT-4, MDR1, EpCAM, and ABCG2) between SP and NSP cells were detected by gastric formation assay and quantitative real-time PCR (3). Oncogenicity of SP and NSP cells was determined in nude mice in vivo. (1) SP cells accounted for 0.1-1.0% of HGC-27 cells, and decreased to 0% after verapamil inhibition. Using flow cytometry, we sorted 7.5×10⁵ SP cells and most HGC-27 cells were NSP cells (2). Gastric formation assay and MTT demonstrated that there was a significant difference in proliferation between SP and NSP cells. Gene expression analysis showed that the expression of genes was significantly higher in SP cells (3). The oncogenicity experiment in nude mice revealed that 105 SP cells were able to form tumors, which demonstrated higher tumorigenicity than non-SP cells. These results collectively suggested that SP cells from HGC-27 cell line have some cancer stem cell properties and could be used for studying the pathogenesis of gastric cancer, which may contribute to discovery of novel therapeutic targets.

  11. Reprogramming cancer cells: a novel approach for cancer therapy or a tool for disease-modeling? (United States)

    Yilmazer, Açelya; de Lázaro, Irene; Taheri, Hadiseh


    Chromatin dynamics have been the major focus of many physiological and pathological processes over the past 20 years. Epigenetic mechanisms have been shown to be reshaped during both cellular reprogramming and tumorigenesis. For this reason, cancer cell reprogramming can provide a powerful tool to better understand both regenerative and cancer-fate processes, with a potential to develop novel therapeutic approaches. Recent studies showed that cancer cells can be reprogrammed to a pluripotent state by the overexpression of reprogramming transcription factors. Activation of transcription factors and modification of chromatin regulators may result in the remodeling of epigenetic status and refueling of tumorigenicity in these reprogrammed cancer cells. However, studies focusing on cancer cell reprogramming are contradictory; some studies reported increased tumor progression whereas others showed that cellular reprogramming has a treatment potential for cancer. In this review, first, the current knowledge on the epigenetic mechanisms involved during cancer development and cellular reprogramming will be presented. Later, different reports and key factors about pluripotency-based reprogramming of cancer cells will be reviewed in detail. New insights will be provided on cancer biology and therapy in the light of cellular reprogramming. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  12. Urothelial cancer stem cells and epithelial plasticity: current concepts and therapeutic implications in bladder cancer. (United States)

    Garg, Minal


    Urothelial carcinoma is a highly heterogeneous disease that develops along two distinct biological tracks as evident by candidate gene analysis and genome-wide screening and therefore, offers different challenges for clinical management. Tumors representing the truly distinct molecular entities express molecular markers characteristic of a developmental process and a major mechanism of cancer metastasis, known as epithelial-to-mesenchymal transition (EMT). Recently identified subset of cells known as urothelial cancer stem cells (UroCSCs) in urothelial cell carcinoma (UCC) have self-renewal properties, ability to generate cellular tumor heterogeneity via differentiation and are ultimately responsible for tumor growth and viability. In this review paper, PubMed and Google Scholar electronic databases were searched for original research papers and review articles to extract relevant information on the molecular mechanisms delineating the relationship between EMT and cancer stemness and their clinical implications for different subsets of urothelial cell carcinomas. Experimental and clinical studies over the past few years in bladder cancer cell lines and tumor tissues of different cancer subtypes provide evidences and new insights for mechanistic complexity for induction of EMT, tumorigenicity, and cancer stemness in malignant transformation of urothelial cell carcinomas. Differentiation and elimination therapies targeting EMT-cancer stemness pathway have been proposed as cynosure in the molecular biology of urothelial cell carcinomas and could prove to be clinically beneficial in an ability to reverse the EMT phenotype of tumor cells, suppress the properties of UroCSCs, inhibit bladder cancer progression and tumor relapse, and provide rationale in the treatment and clinical management of urothelial cancer.

  13. Cell biology apps for Apple devices. (United States)

    Stark, Louisa A


    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.

  14. The kisspeptin (KiSS-1)/GPR54 system in cancer biology. (United States)

    Makri, Angeliki; Pissimissis, Nikolaos; Lembessis, Peter; Polychronakos, Constantine; Koutsilieris, Michael


    Kisspeptin (KiSS-1) gene, initially described as a melanoma metastasis suppressor gene, encodes a number of peptides (kp-54, kp-14, kp-13, kp-10), which are endogenous ligands to a G protein-coupled receptor, referred as hOT7T175 or AXOR12 or GPR54. So far intensive investigation has provided substantiate evidence supporting the role of KiSS-1/GPR54 system in cancer biology as well as in the regulation of the reproductive function and trophoblast invasion. The precise mechanism by which KiSS-1/GPR54 system is affecting cancer cell growth and metastasis includes complex endocrine, paracrine and autocrine actions. Nevertheless, the detail mechanism of such actions is still under intensive investigation. Herein we review the evidence which support the role of KiSS-1/GPR54 system in cancer biology.

  15. Reprogramming cancer cells: overview & current progress. (United States)

    Lim, Kian Lam; Teoh, Hoon Koon; Choong, Pei Feng; Teh, Hui Xin; Cheong, Soon Keng; Kamarul, Tunku


    Cancer is a disease with genetic and epigenetic origins, and the possible effects of reprogramming cancer cells using the defined sets of transcription factors remain largely uninvestigated. In the handful of publications available so far, findings have shown that reprogramming cancer cells changed the characteristics of the cells to differ from the parental cancer cells. These findings indicated the possibility of utilizing reprogramming technology to create a disease model in the laboratory to be used in studying the molecular pathogenesis or for drug screening of a particular cancer model. Despite numerous methods employed in generating induced pluripotent stem cells (iPSCs) from cancer cells only a few studies have successfully reprogrammed malignant human cells. In this review we will provide an overview on i) methods to reprogram cancer cells, ii) characterization of the reprogrammed cancer cells, and iii) the differential effects of reprogramming on malignancy, epigenetics and response of the cancer cells to chemotherapeutic agents. Continued technical progress in cancer cell reprogramming technology will be instrumental for more refined in vitro disease models and ultimately for the development of directed and personalized therapy for cancer patients in the future.

  16. The evolving concepts of cancer stem cells in head and neck squamous cell carcinoma. (United States)

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


    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 design of novel treatments targeted toward these cells. The present review is an attempt to conceptualize the role of CSCs in HNSCC--its implication in tumorigenesis and the possible additional approach in current treatment strategies.

  17. Glycoengineering in CHO cells: Advances in systems biology

    DEFF Research Database (Denmark)

    Tejwani, Vijay; Andersen, Mikael Rørdam; Nam, Jong Hyun


    For several decades, glycoprotein biologics have been successfully produced from Chinese hamster ovary (CHO) cells. The therapeutic efficacy and potency of glycoprotein biologics are often dictated by their post translational modifications, particularly glycosylation, which unlike protein synthesis...

  18. Breast cancer biology and ethnic disparities in breast cancer mortality in new zealand: a cohort study. (United States)

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


    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 cancer

  19. MYC function and regulation in flies: how Drosophila has enlightened MYC cancer biology

    Directory of Open Access Journals (Sweden)

    Jue Er Amanda Lee


    Full Text Available Progress in our understanding of the complex signaling events driving human cancer would have been unimaginably slow without discoveries from Drosophila genetic studies. Significantly, many of the signaling pathways now synonymous with cancer biology were first identified as a result of elegant screens for genes fundamental to metazoan development. Indeed the name given to many core cancer-signaling cascades tells of their history as developmental patterning regulators in flies—e.g. Wingless (Wnt, Notch and Hippo. Moreover, astonishing insight has been gained into these complex signaling networks, and many other classic oncogenic signaling networks (e.g. EGFR/RAS/RAF/ERK, InR/PI3K/AKT/TOR, using sophisticated fly genetics. Of course if we are to understand how these signaling pathways drive cancer, we must determine the downstream program(s of gene expression activated to promote the cell and tissue over growth fundamental to cancer. Here we discuss one commonality between each of these pathways: they are all implicated as upstream activators of the highly conserved MYC oncogene and transcription factor. MYC can drive all aspects of cell growth and cell cycle progression during animal development. MYC is estimated to be dysregulated in over 50% of all cancers, underscoring the importance of elucidating the signals activating MYC. We also discuss the FUBP1/FIR/FUSE system, which acts as a ‘cruise control’ on the MYC promoter to control RNA Polymerase II pausing and, therefore, MYC transcription in response to the developmental signaling environment. Importantly, the striking conservation between humans and flies within these major axes of MYC regulation has made Drosophila an extremely valuable model organism for cancer research. We therefore discuss how Drosophila studies have helped determine the validity of signaling pathways regulating MYC in vivo using sophisticated genetics, and continue to provide novel insight into cancer biology.

  20. The emerging age of cell-free synthetic biology. (United States)

    Smith, Mark Thomas; Wilding, Kristen M; Hunt, Jeremy M; Bennett, Anthony M; Bundy, Bradley C


    The engineering of and mastery over biological parts has catalyzed the emergence of synthetic biology. This field has grown exponentially in the past decade. As increasingly more applications of synthetic biology are pursued, more challenges are encountered, such as delivering genetic material into cells and optimizing genetic circuits in vivo. An in vitro or cell-free approach to synthetic biology simplifies and avoids many of the pitfalls of in vivo synthetic biology. In this review, we describe some of the innate features that make cell-free systems compelling platforms for synthetic biology and discuss emerging improvements of cell-free technologies. We also select and highlight recent and emerging applications of cell-free synthetic biology. Copyright © 2014 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.

  1. 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.


    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

  2. Capecitabine treatment of HCT-15 colon cancer cells induces ...

    African Journals Online (AJOL)

    Capecitabine treatment of HCT-15 colon cancer cells induces apoptosis via mitochondrial pathway. Mingli Li1*, Na Zhang2 and Mingxuan Li3. 1Biology and Medicine, 2Pharmaceutics, Shandong University, Shandong 250100, 3Department of Nursing, Affiliated Hospital of. Jining Medical University, Jining, Shandong ...

  3. Using Mouse Mammary Tumor Cells to Teach Core Biology Concepts: A Simple Lab Module. (United States)

    McIlrath, Victoria; Trye, Alice; Aguanno, Ann


    Undergraduate biology students are required to learn, understand and apply a variety of cellular and molecular biology concepts and techniques in preparation for biomedical, graduate and professional programs or careers in science. To address this, a simple laboratory module was devised to teach the concepts of cell division, cellular communication and cancer through the application of animal cell culture techniques. Here the mouse mammary tumor (MMT) cell line is used to model for breast cancer. Students learn to grow and characterize these animal cells in culture and test the effects of traditional and non-traditional chemotherapy agents on cell proliferation. Specifically, students determine the optimal cell concentration for plating and growing cells, learn how to prepare and dilute drug solutions, identify the best dosage and treatment time course of the antiproliferative agents, and ascertain the rate of cell death in response to various treatments. The module employs both a standard cell counting technique using a hemocytometer and a novel cell counting method using microscopy software. The experimental procedure lends to open-ended inquiry as students can modify critical steps of the protocol, including testing homeopathic agents and over-the-counter drugs. In short, this lab module requires students to use the scientific process to apply their knowledge of the cell cycle, cellular signaling pathways, cancer and modes of treatment, all while developing an array of laboratory skills including cell culture and analysis of experimental data not routinely taught in the undergraduate classroom.

  4. Cancer stem cells: the theory and perspectives in cancer therapy. (United States)

    Gil, Justyna; Stembalska, Agnieszka; Pesz, Karolina A; Sasiadek, Maria M


    The cancer stem cell theory elucidates not only the issue of tumour initiation and development, tumour's ability to metastasise and reoccur, but also the ineffectiveness of conventional cancer therapy. This review examines stem cell properties, such as self-renewal, heterogeneity, and resistance to apoptosis. The 'niche' hypothesis is presented, and mechanisms of division, differentiation, self-renewal and signalling pathway regulation are explained. Epigenetic alterations and mutations of genes responsible for signal transmission may promote the formation of cancer stem cells. We also present the history of development of the cancer stem cell theory and discuss the experiments that led to the discovery and confirmation of the existence of cancer stem cells. Potential clinical applications are also considered, including therapeutic models aimed at selective elimination of cancer stem cells or induction of their proper differentiation.

  5. Cell-free synthetic biology: Engineering in an open world. (United States)

    Lu, Yuan


    Cell-free synthetic biology emerges as a powerful and flexible enabling technology that can engineer biological parts and systems for life science applications without using living cells. It provides simpler and faster engineering solutions with an unprecedented freedom of design in an open environment than cell system. This review focuses on recent developments of cell-free synthetic biology on biological engineering fields at molecular and cellular levels, including protein engineering, metabolic engineering, and artificial cell engineering. In cell-free protein engineering, the direct control of reaction conditions in cell-free system allows for easy synthesis of complex proteins, toxic proteins, membrane proteins, and novel proteins with unnatural amino acids. Cell-free systems offer the ability to design metabolic pathways towards the production of desired products. Buildup of artificial cells based on cell-free systems will improve our understanding of life and use them for environmental and biomedical applications.

  6. Cell-free synthetic biology: Engineering in an open world

    Directory of Open Access Journals (Sweden)

    Yuan Lu


    Full Text Available Cell-free synthetic biology emerges as a powerful and flexible enabling technology that can engineer biological parts and systems for life science applications without using living cells. It provides simpler and faster engineering solutions with an unprecedented freedom of design in an open environment than cell system. This review focuses on recent developments of cell-free synthetic biology on biological engineering fields at molecular and cellular levels, including protein engineering, metabolic engineering, and artificial cell engineering. In cell-free protein engineering, the direct control of reaction conditions in cell-free system allows for easy synthesis of complex proteins, toxic proteins, membrane proteins, and novel proteins with unnatural amino acids. Cell-free systems offer the ability to design metabolic pathways towards the production of desired products. Buildup of artificial cells based on cell-free systems will improve our understanding of life and use them for environmental and biomedical applications.

  7. Cell Biology of Thiazide Bone Effects (United States)

    Gamba, Gerardo; Riccardi, Daniela


    The thiazide-sensitive Na+:Cl- cotransporter (NCC) is the major pathway for salt reabsorption in the mammalian kidney. The activity of NCC is not only related to salt metabolism, but also to calcium and magnesium homeostasis due to the inverse relationship between NCC activity and calcium reabsorption. Hence, the thiazide-type diuretics that specifically block NCC have been used for years, not only for treatment of hypertension and edematous disease, but also for the management of renal stone disease. Epidemiological studies have shown that chronic thiazide treatment is associated with higher bone mineral density and reduced risk of bone fractures, which can only partly be explained in terms of their effects on the kidney. In this regard, we have recently shown that NCC is expressed in bone cells and that inhibition of NCC in bone, either by thiazides or by reduction of NCC protein with specific siRNA, is associated with increased mineralization in vitro. These observations open a field of study to begin to understand the cell biology of the beneficial effects of thiazides in bone.

  8. Pancreatic cancer biology and genetics from an evolutionary perspective. (United States)

    Makohon-Moore, Alvin; Iacobuzio-Donahue, Christine A


    Cancer is an evolutionary disease, containing the hallmarks of an asexually reproducing unicellular organism subject to evolutionary paradigms. Pancreatic ductal adenocarcinoma (hereafter referred to as pancreatic cancer) is a particularly robust example of this phenomenon. Genomic features indicate that pancreatic cancer cells are selected for fitness advantages when encountering the geographic and resource-depleted constraints of the microenvironment. Phenotypic adaptations to these pressures help disseminated cells to survive in secondary sites, a major clinical problem for patients with this disease. In this Review we gather the wide-ranging aspects of pancreatic cancer research into a single concept rooted in Darwinian evolution, with the goal of identifying novel insights and opportunities for study.

  9. Pancreatic cancer biology and genetics from an evolutionary perspective (United States)

    Makohon-Moore, Alvin; Iacobuzio-Donahue, Christine A.


    Cancer is an evolutionary disease, containing the hallmarks of an asexually reproducing unicellular organism subject to evolutionary paradigms. Pancreatic ductal adenocarcinoma (hereafter referred to as pancreatic cancer) is a particularly robust example of this phenomenon. Genomic features indicate that pancreatic cancer cells are selected for fitness advantages when encountering the geographic and resource-depleted constraints of the microenvironment. Phenotypic adaptations to these pressures help disseminated cells to survive in secondary sites, a major clinical problem for patients with this disease. In this Review we gather the wide-ranging aspects of pancreatic cancer research into a single concept rooted in Darwinian evolution, with the goal of identifying novel insights and opportunities for study. PMID:27444064

  10. A POX on Renal Cancer Cells | Center for Cancer Research (United States)

    Proline oxidase, or POX, is an enzyme responsible for metabolizing the amino acid proline. POX contributes to the regulation of cell death that occurs when cellular systems malfunction, a process called apoptosis. Previous studies have determined that levels of POX are reduced in several types of human cancer. Likewise, many cancer cells become resistant to apoptosis, suggesting a link between POX and cancer cell survival.

  11. Mammary Development and Breast Cancer: The Role of Stem Cells (United States)

    Ercan, C.; van Diest, P.J.; Vooijs, M.


    The mammary gland is a highly regenerative organ that can undergo multiple cycles of proliferation, lactation and involution, a process controlled by stem cells. The last decade much progress has been made in the identification of signaling pathways that function in these stem cells to control self-renewal, lineage commitment and epithelial differentiation in the normal mammary gland. The same signaling pathways that control physiological mammary development and homeostasis are also often found deregulated in breast cancer. Here we provide an overview on the functional and molecular identification of mammary stem cells in the context of both normal breast development and breast cancer. We discuss the contribution of some key signaling pathways with an emphasis on Notch receptor signaling, a cell fate determination pathway often deregulated in breast cancer. A further understanding of the biological roles of the Notch pathway in mammary stem cell behavior and carcinogenesis might be relevant for the development of future therapies. PMID:21506923

  12. Spatiotemporal dynamics of the biological interface between cancer and the microenvironment: a fractal anomalous diffusion model with microenvironment plasticity

    Directory of Open Access Journals (Sweden)

    Tsai Feng-Chou


    Full Text Available Abstract Background The invasion-metastasis cascade of cancer involves a process of parallel progression. A biological interface (module in which cells is linked with ECM (extracellular matrix by CAMs (cell adhesion molecules has been proposed as a tool for tracing cancer spatiotemporal dynamics. Methods A mathematical model was established to simulate cancer cell migration. Human uterine leiomyoma specimens, in vitro cell migration assay, quantitative real-time PCR, western blotting, dynamic viscosity, and an in vivo C57BL6 mouse model were used to verify the predictive findings of our model. Results The return to origin probability (RTOP and its related CAM expression ratio in tumors, so-called "tumor self-seeding", gradually decreased with increased tumor size, and approached the 3D Pólya random walk constant (0.340537 in a periodic structure. The biphasic pattern of cancer cell migration revealed that cancer cells initially grew together and subsequently began spreading. A higher viscosity of fillers applied to the cancer surface was associated with a significantly greater inhibitory effect on cancer migration, in accordance with the Stokes-Einstein equation. Conclusion The positional probability and cell-CAM-ECM interface (module in the fractal framework helped us decipher cancer spatiotemporal dynamics; in addition we modeled the methods of cancer control by manipulating the microenvironment plasticity or inhibiting the CAM expression to the Pólya random walk, Pólya constant.

  13. 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: [Department of Biomedical Science, College of Life Science, CHA University, Seoul (Korea, Republic of)


    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.

  14. Integrating cell biology and proteomic approaches in plants. (United States)

    Takáč, Tomáš; Šamajová, Olga; Šamaj, Jozef


    Significant improvements of protein extraction, separation, mass spectrometry and bioinformatics nurtured advancements of proteomics during the past years. The usefulness of proteomics in the investigation of biological problems can be enhanced by integration with other experimental methods from cell biology, genetics, biochemistry, pharmacology, molecular biology and other omics approaches including transcriptomics and metabolomics. This review aims to summarize current trends integrating cell biology and proteomics in plant science. Cell biology approaches are most frequently used in proteomic studies investigating subcellular and developmental proteomes, however, they were also employed in proteomic studies exploring abiotic and biotic stress responses, vesicular transport, cytoskeleton and protein posttranslational modifications. They are used either for detailed cellular or ultrastructural characterization of the object subjected to proteomic study, validation of proteomic results or to expand proteomic data. In this respect, a broad spectrum of methods is employed to support proteomic studies including ultrastructural electron microscopy studies, histochemical staining, immunochemical localization, in vivo imaging of fluorescently tagged proteins and visualization of protein-protein interactions. Thus, cell biological observations on fixed or living cell compartments, cells, tissues and organs are feasible, and in some cases fundamental for the validation and complementation of proteomic data. Validation of proteomic data by independent experimental methods requires development of new complementary approaches. Benefits of cell biology methods and techniques are not sufficiently highlighted in current proteomic studies. This encouraged us to review most popular cell biology methods used in proteomic studies and to evaluate their relevance and potential for proteomic data validation and enrichment of purely proteomic analyses. We also provide examples of

  15. Insights into the key roles of proteoglycans in breast cancer biology and translational medicine. (United States)

    Theocharis, Achilleas D; Skandalis, Spyros S; Neill, Thomas; Multhaupt, Hinke A B; Hubo, Mario; Frey, Helena; Gopal, Sandeep; Gomes, Angélica; Afratis, Nikos; Lim, Hooi Ching; Couchman, John R; Filmus, Jorge; Sanderson, Ralph D; Schaefer, Liliana; Iozzo, Renato V; Karamanos, Nikos K


    Proteoglycans control numerous normal and pathological processes, among which are morphogenesis, tissue repair, inflammation, vascularization and cancer metastasis. During tumor development and growth, proteoglycan expression is markedly modified in the tumor microenvironment. Altered expression of proteoglycans on tumor and stromal cell membranes affects cancer cell signaling, growth and survival, cell adhesion, migration and angiogenesis. Despite the high complexity and heterogeneity of breast cancer, the rapid evolution in our knowledge that proteoglycans are among the key players in the breast tumor microenvironment suggests their potential as pharmacological targets in this type of cancer. It has been recently suggested that pharmacological treatment may target proteoglycan metabolism, their utilization as targets for immunotherapy or their direct use as therapeutic agents. The diversity inherent in the proteoglycans that will be presented herein provides the potential for multiple layers of regulation of breast tumor behavior. This review summarizes recent developments concerning the biology of selected proteoglycans in breast cancer, and presents potential targeted therapeutic approaches based on their novel key roles in breast cancer. Copyright © 2015 Elsevier B.V. All rights reserved.

  16. Ubc9 promotes invasion and metastasis of lung cancer cells. (United States)

    Li, Hui; Niu, Huiyan; Peng, Yang; Wang, Jiahe; He, Ping


    Lung cancer is the leading cause of cancer-related mortality worldwide. The mortality is high mainly due to the lack of known effective screening procedures; there is a high tendency for early spread and systemic therapies do not cure metastatic disease. Thus, it is important to investigate the molecular mechanism(s) of lung cancer development and, specifically, to identify an effective method by which to inhibit the invasion and metastasis of lung cancer. Ubiquitin-conjugating enzyme 9 (Ubc9), the sole conjugating enzyme for sumoylation, regulates protein function and plays a key role in tumorigenesis. Whether Ubc9 is involved in the invasion and metastasis of lung cancer remains unknown. Herein, we report that Ubc9 exhibits an important role in lung cancer invasion and metastasis. We first investigated the biological effect of Ubc9 on lung cancer by cloning the Ubc9 gene into a eukaryotic expression plasmid and stably expressing it in the human small cell lung cancer cell line NCI-H446 in order to observe any biological changes. We further analyzed the effect of Ubc9 in an in vivo experiment, injecting NCI-H446 cells stably overexpressing Ubc9 into nude mice and analyzing their metastatic ability. Our results demonstrated that Ubc9 is expressed at higher levels in primary lung cancer tissue and metastatic nodules as compared to premalignant and/or normal tissue. Furthermore, we demonstrated that upregulation of Ubc9 expression promotes migration and invasion. Ubc9 likely plays an important role in cancer progression by promoting invasion and metastasis in lung cancer.

  17. Biology of the adult hepatic progenitor cell: "ghosts in the machine". (United States)

    Darwiche, Houda; Petersen, Bryon E


    This chapter reviews some of the basic biological principles governing adult progenitor cells of the liver and the mechanisms by which they operate. If scientists were better able to understand the conditions that govern stem cell mechanics in the liver, it may be possible to apply that understanding in a clinical setting for use in the treatment or cure of human pathologies. This chapter gives a basic introduction to hepatic progenitor cell biology and explores what is known about progenitor cell-mediated liver regeneration. We also discuss the putative stem cell niche in the liver, as well as the signaling pathways involved in stem cell regulation. Finally, the isolation and clinical application of stem cells to human diseases is reviewed, along with the current thoughts on the relationship between stem cells and cancer. Copyright © 2010 Elsevier Inc. All rights reserved.

  18. Targeting cancer stem cells: emerging role of Nanog transcription factor

    Directory of Open Access Journals (Sweden)

    Wang ML


    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

  19. Open questions: The disrupted circuitry of the cancer cell

    Energy Technology Data Exchange (ETDEWEB)

    Wiley, H. S.


    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.

  20. Molecular imaging of prostate cancer: translating molecular biology approaches into the clinical realm. (United States)

    Vargas, Hebert Alberto; Grimm, Jan; F Donati, Olivio; Sala, Evis; Hricak, Hedvig


    The epidemiology of prostate cancer has dramatically changed since the introduction of prostate-specific antigen (PSA) screening in the 1980's. Most prostate cancers today are detected at early stages of the disease and are considered 'indolent'; however, some patients' prostate cancers demonstrate a more aggressive behaviour which leads to rapid progression and death. Increasing understanding of the biology underlying the heterogeneity that characterises this disease has led to a continuously evolving role of imaging in the management of prostate cancer. Functional and metabolic imaging techniques are gaining importance as the impact on the therapeutic paradigm has shifted from structural tumour detection alone to distinguishing patients with indolent tumours that can be managed conservatively (e.g., by active surveillance) from patients with more aggressive tumours that may require definitive treatment with surgery or radiation. In this review, we discuss advanced imaging techniques that allow direct visualisation of molecular interactions relevant to prostate cancer and their potential for translation to the clinical setting in the near future. The potential use of imaging to follow molecular events during drug therapy as well as the use of imaging agents for therapeutic purposes will also be discussed. • Advanced imaging techniques allow direct visualisation of molecular interactions in prostate cancer. • MRI/PET, optical and Cerenkov imaging facilitate the translation of molecular biology. • Multiple compounds targeting PSMA expression are currently undergoing clinical translation. • Other targets (e.g., PSA, prostate-stem cell antigen, GRPR) are in development.

  1. [Biological function of cancer-associated carbohydrate antigens]. (United States)

    Kannagi, R


    An important outcome of the monoclonal antibody approach for cancer-associated antigens is that cell-surface carbohydrates have been shown to be very important cancer-associated antigens. These antigens are currently classified into several groups. The first group has the sugar determinant carried by so-called type 1 chain carbohydrates, with a backbone structure composed of the Gal beta 1-->3GlcNAc beta repeating unit. The antigens in this group are utilized mainly for the diagnosis of cancers in the pancreas, biliary tract and other digestive organs. This group includes the well-known serum tumor marker, the 2 -->3 sialyl Le(a) antigen, which is detected by N19-9 and other antibodies. This group also includes DU-PAN-2, which was recently confirmed to be the sialyl Lec. The second group has the polysaccharide determinant carried by so-called type 2 chain carbohydrates, the characteristic feature of which is a backbone structure composed of the Gal beta1 -->4GlcNAc beta repeating unit. This group includes the tumor markers, sialyl SSEA-1, CSLEX-1 or sialyl Lewis X, and is used for the diagnosis of cancers originating in the lung, ovary and digestive organs. The third group has the antigenic determinant carried by the innermost core structures in O-linked carbohydrate side chains. The example of this group is the sialyl Tn antigen, which is detected in ovarian cancers. This group also includes the recently described carbohydrate determinant called Fl alpha antigen, which is frequently expressed in gastric cancer cells. Some of the antigens in the first and second groups such as sialyl Le(a) and sialyl Le(x), serve as ligands for E-selectin, a cell adhesion molecule expressed on activated human endothelial cells, and play significant roles in hematogenous metastasis of cancer.

  2. Of mice and women: a comparative tissue biology perspective of breast stem cells and differentiation. (United States)

    Dontu, Gabriela; Ince, Tan A


    Tissue based research requires a background in human and veterinary pathology, developmental biology, anatomy, as well as molecular and cellular biology. This type of comparative tissue biology (CTB) expertise is necessary to tackle some of the conceptual challenges in human breast stem cell research. It is our opinion that the scarcity of CTB expertise contributed to some erroneous interpretations in tissue based research, some of which are reviewed here in the context of breast stem cells. In this article we examine the dissimilarities between mouse and human mammary tissue and suggest how these may impact stem cell studies. In addition, we consider the differences between breast ducts vs. lobules and clarify how these affect the interpretation of results in stem cell research. Lastly, we introduce a new elaboration of normal epithelial cell types in human breast and discuss how this provides a clinically useful basis for breast cancer classification.

  3. The Effect of Biologically Effective Dose and Radiation Treatment Schedule on Overall Survival in Stage I Non-Small Cell Lung Cancer Patients Treated With Stereotactic Body Radiation Therapy

    Energy Technology Data Exchange (ETDEWEB)

    Stahl, John M. [Department of Therapeutic Radiology, Yale School of Medicine, New Haven, Connecticut (United States); Ross, Rudi [21st Century Oncology, Fort Myers, Florida (United States); Harder, Eileen M.; Mancini, Brandon R. [Department of Therapeutic Radiology, Yale School of Medicine, New Haven, Connecticut (United States); Soulos, Pamela R. [Cancer Outcomes, Public Policy and Effectiveness Research (COPPER) Center, Yale School of Medicine, New Haven, Connecticut (United States); Finkelstein, Steven E.; Shafman, Timothy D.; Dosoretz, Arie P. [21st Century Oncology, Fort Myers, Florida (United States); Evans, Suzanne B.; Husain, Zain A.; Yu, James B. [Department of Therapeutic Radiology, Yale School of Medicine, New Haven, Connecticut (United States); Gross, Cary P. [Cancer Outcomes, Public Policy and Effectiveness Research (COPPER) Center, Yale School of Medicine, New Haven, Connecticut (United States); Decker, Roy H., E-mail: [Department of Therapeutic Radiology, Yale School of Medicine, New Haven, Connecticut (United States)


    Purpose: To determine the effect of biologically effective dose (BED{sub 10}) and radiation treatment schedule on overall survival (OS) in patients with early-stage non-small cell lung cancer (NSCLC) undergoing stereotactic body radiation therapy (SBRT). Methods and Materials: Using data from 65 treatment centers in the United States, we retrospectively reviewed the records of T1-2 N0 NSCLC patients undergoing SBRT alone from 2006 to 2014. Biologically relevant covariates, including dose per fraction, number of fractions, and time between fractions, were used to quantify BED{sub 10} and radiation treatment schedule. The linear-quadratic equation was used to calculate BED{sub 10} and to generate a dichotomous dose variable of <105 Gy versus ≥105 Gy BED{sub 10}. The primary outcome was OS. We used the Kaplan-Meier method, the log–rank test, and Cox proportional hazards regression with propensity score matching to determine whether prescription BED{sub 10} was associated with OS. Results: We identified 747 patients who met inclusion criteria. The median BED{sub 10} was 132 Gy, and 59 (7.7%) had consecutive-day fractions. Median follow-up was 41 months, and 452 patients (60.5%) had died by the conclusion of the study. The 581 patients receiving ≥105 Gy BED{sub 10} had a median survival of 28 months, whereas the 166 patients receiving <105 Gy BED{sub 10} had a median survival of 22 months (log–rank, P=.01). Radiation treatment schedule was not a significant predictor of OS on univariable analysis. After adjusting for T stage, sex, tumor histology, and Eastern Cooperative Oncology Group performance status, BED{sub 10} ≥105 Gy versus <105 Gy remained significantly associated with improved OS (hazard ratio 0.78, 95% confidence interval 0.62-0.98, P=.03). Propensity score matching on imbalanced variables within high- and low-dose cohorts confirmed a survival benefit with higher prescription dose. Conclusions: We found that dose escalation to 105 Gy BED

  4. Prostate Cancer Stem-Like Cells | Center for Cancer Research (United States)

    Prostate cancer is the third leading cause of cancer-related death among men, killing an estimated 27,000 men each year in the United States. Men with advanced prostate cancer often become resistant to conventional therapies. Many researchers speculate that the emergence of resistance is due to the presence of cancer stem cells, which are believed to be a small subpopulation of tumor cells that can self-renew and give rise to more differentiated tumor cells. It is thought that these stem cells survive initial therapies (such as chemotherapy and hormone therapy) and then generate new tumor cells that are resistant to these standard treatments. If prostate cancer stem cells could be identified and characterized, it might be possible to design treatments that prevent resistance.

  5. Cell Biology of Cnidarian-Dinoflagellate Symbiosis (United States)

    Allemand, Denis; Weis, Virginia M.


    Summary: The symbiosis between cnidarians (e.g., corals or sea anemones) and intracellular dinoflagellate algae of the genus Symbiodinium is of immense ecological importance. In particular, this symbiosis promotes the growth and survival of reef corals in nutrient-poor tropical waters; indeed, coral reefs could not exist without this symbiosis. However, our fundamental understanding of the cnidarian-dinoflagellate symbiosis and of its links to coral calcification remains poor. Here we review what we currently know about the cell biology of cnidarian-dinoflagellate symbiosis. In doing so, we aim to refocus attention on fundamental cellular aspects that have been somewhat neglected since the early to mid-1980s, when a more ecological approach began to dominate. We review the four major processes that we believe underlie the various phases of establishment and persistence in the cnidarian/coral-dinoflagellate symbiosis: (i) recognition and phagocytosis, (ii) regulation of host-symbiont biomass, (iii) metabolic exchange and nutrient trafficking, and (iv) calcification. Where appropriate, we draw upon examples from a range of cnidarian-alga symbioses, including the symbiosis between green Hydra and its intracellular chlorophyte symbiont, which has considerable potential to inform our understanding of the cnidarian-dinoflagellate symbiosis. Ultimately, we provide a comprehensive overview of the history of the field, its current status, and where it should be going in the future. PMID:22688813

  6. Genome Annotation in a Community College Cell Biology Lab (United States)

    Beagley, C. Timothy


    The Biology Department at Salt Lake Community College has used the IMG-ACT toolbox to introduce a genome mapping and annotation exercise into the laboratory portion of its Cell Biology course. This project provides students with an authentic inquiry-based learning experience while introducing them to computational biology and contemporary learning…

  7. Nanoparticle characterization for cancer nanotechnology and other biological applications. (United States)

    Brown, Scott C; Palazuelos, Maria; Sharma, Parvesh; Powers, Kevin W; Roberts, Stephen M; Grobmyer, Stephen R; Moudgil, Brij M


    Nanotechnology is actively being used to develop promising diagnostics and therapeutics tools for the treatment of cancer and many other diseases. The unique properties of nanomaterials offer an exciting frontier of possibilities for biomedical researchers and scientists. Because existing knowledge of macroscopic materials does not always allow for adequate prediction of the characteristics and behaviors of nanoscale materials in controlled environments, much less in biological systems, careful nanoparticle characterization should accompany biomedical applications of these materials. Informed correlations between adequately characterized nanomaterial properties and reliable biological endpoints are essential for guiding present and future researchers toward clinical nanotechnology-based solutions for cancer. Biological environments are notoriously dynamic; hence, nanoparticulate interactions within these environments will likely be comparatively diverse. For this reason, we recommend that an interactive and systematic approach to material characterization be taken when attempting to elucidate or measure biological interactions with nanoscale materials. We intend for this chapter to be a practical guide that could be used by researchers to identify key nanomaterial characteristics that require measurement for their systems and the appropriate techniques to perform those measurements. Each section includes a basic overview of each measurement and notes on how to address some of the common difficulties associated with nanomaterial characterization.

  8. Cancer Cell Fusion: Mechanisms Slowly Unravel

    Directory of Open Access Journals (Sweden)

    Felicite K. Noubissi


    Full Text Available Although molecular mechanisms and signaling pathways driving invasion and metastasis have been studied for many years, the origin of the population of metastatic cells within the primary tumor is still not well understood. About a century ago, Aichel proposed that cancer cell fusion was a mechanism of cancer metastasis. This hypothesis gained some support over the years, and recently became the focus of many studies that revealed increasing evidence pointing to the possibility that cancer cell fusion probably gives rise to the metastatic phenotype by generating widespread genetic and epigenetic diversity, leading to the emergence of critical populations needed to evolve resistance to the treatment and development of metastasis. In this review, we will discuss the clinical relevance of cancer cell fusion, describe emerging mechanisms of cancer cell fusion, address why inhibiting cancer cell fusion could represent a critical line of attack to limit drug resistance and to prevent metastasis, and suggest one new modality for doing so.

  9. Synthetic Biology: A Bridge between Artificial and Natural Cells


    Yunfeng Ding; Fan Wu; Cheemeng Tan


    Artificial cells are simple cell-like entities that possess certain properties of natural cells. In general, artificial cells are constructed using three parts: (1) biological membranes that serve as protective barriers, while allowing communication between the cells and the environment; (2) transcription and translation machinery that synthesize proteins based on genetic sequences; and (3) genetic modules that control the dynamics of the whole cell. Artificial cells are minimal and well-defi...

  10. Field cancerization in non-small cell lung cancer: implications in disease pathogenesis. (United States)

    Kadara, Humam; Wistuba, Ignacio I


    Lung cancer, of which non-small cell lung cancer (NSCLC) composes the majority, is the leading cause of cancer-related deaths in the United States and worldwide. NSCLCs are tumors with complex biology that we have recently started to understand with the advent of various histological, transcriptomic, genomic, and proteomic technologies. However, the histological and molecular pathogenesis of this malignancy, in particular of adenocarcinomas, is still largely unknown. Earlier studies have highlighted a field cancerization phenomenon in which histologically normal-appearing tissue adjacent to neoplastic and pre-neoplastic lesions display molecular abnormalities, some of which are in common with those in the tumors. This review will summarize advances in understanding the field cancerization phenomenon and the potential relevance of this knowledge to gain important and novel insights into the molecular pathogenesis of NSCLC as well as to subsequent development of biomarkers for early detection of lung cancers and possibly personalized prevention.

  11. Synthetic biology: programming cells for biomedical applications. (United States)

    Hörner, Maximilian; Reischmann, Nadine; Weber, Wilfried


    The emerging field of synthetic biology is a novel biological discipline at the interface between traditional biology, chemistry, and engineering sciences. Synthetic biology aims at the rational design of complex synthetic biological devices and systems with desired properties by combining compatible, modular biological parts in a systematic manner. While the first engineered systems were mainly proof-of-principle studies to demonstrate the power of the modular engineering approach of synthetic biology, subsequent systems focus on applications in the health, environmental, and energy sectors. This review describes recent approaches for biomedical applications that were developed along the synthetic biology design hierarchy, at the level of individual parts, of devices, and of complex multicellular systems. It describes how synthetic biological parts can be used for the synthesis of drug-delivery tools, how synthetic biological devices can facilitate the discovery of novel drugs, and how multicellular synthetic ecosystems can give insight into population dynamics of parasites and hosts. These examples demonstrate how this new discipline could contribute to novel solutions in the biopharmaceutical industry.

  12. Methyl-donor nutrients inhibit breast cancer cell growth. (United States)

    Park, Chung S; Cho, Kyongshin; Bae, Dong R; Joo, Nam E; Kim, Hyung H; Mabasa, Lawrence; Fowler, Andrea W


    Lipotropes (methyl group containing nutrients, including methionine, choline, folate, and vitamin B(12)) are dietary methyl donors and cofactors that are involved in one-carbon metabolism, which is important for genomic DNA methylation reactions and nucleic acid synthesis. One-carbon metabolism provides methyl groups for all biological methylation pathways and is highly dependent on dietary supplementation of methyl nutrients. Nutrition is an important determinant of breast cancer risk and tumor behavior, and dietary intervention may be an effective approach to prevent breast cancer. Apoptosis is important for the regulation of homeostasis and tumorigenesis. The anti-apoptotic protein Bcl-2 may be a regulatory target in cancer therapy; controlling or modulating its expression may be a therapeutic strategy against breast cancer. In this study, the effects of lipotrope supplementation on the growth and death of human breast cancer cell lines T47D and MCF-7 were examined and found to inhibit growth of both T47D and MCF-7 cells. Furthermore, the ratios of apoptotic cells to the total number of cells were approximately 44% and 34% higher in the lipotrope-supplemented treatments of T47D and MCF-7 cancer cells, respectively, compared with the control treatments. More importantly, Bcl-2 protein expression was decreased by approximately 25% from lipotrope supplementation in T47D cells, suggesting that lipotropes can induce breast cancer cell death by direct downregulation of Bcl-2 protein expression. Cancer treatment failure is often correlated with Bcl-2 protein upregulation. These data may be useful in the development of effective nutritional strategies to prevent and reduce breast cancer in humans.

  13. Nanomaterials for targeted drug delivery to cancer stem cells. (United States)

    Orza, Anamaria; Casciano, Daniel; Biris, Alexandru


    Recent developments in cancer biology have identified the existence of a sub-poplulation of cells - cancer stem cells (CSC) that are resistant to most traditional therapies (e.g. chemotherapy and radiotherapy) and have the ability to repair their damaged DNA. These findings have necessitated a break with traditional oncology management and encouraged new perspectives concerning cancer treatment. Understanding the functional biology of CSCs - especially the signaling pathways that are involved in their self-renewal mechanisms - is crucial for discovering new forms of treatment. In this review, we highlight current and future prospects for potential cancer therapies based on the use of nano-sized materials. Nanomaterials could revolutionize cancer management because of their distinctive features - unique surface chemistry, strong electronic, optic, and magnetic properties - that are found neither in bulk materials nor in single molecules. Based on these distinct properties, we believe that nanomaterials could be excellent candidates for use in CSC research in order to optimize cancer therapeutics. Moreover, we propose these nanomaterials for the inhibition of the self-renewal pathways of CSCs by focusing on the Hedgehog, Notch, and Wnt/β-catenin self-renewal mechanisms. By introducing these methods for the detection, targeting, and destruction of CSCs, an efficient alternative treatment for the incurable disease of cancer could be provided.

  14. Epithelial to mesenchymal transition is mechanistically linked with stem cell signatures in prostate cancer cells.

    Directory of Open Access Journals (Sweden)

    Dejuan Kong

    Full Text Available BACKGROUND: Current management of patients diagnosed with prostate cancer (PCa is very effective; however, tumor recurrence with Castrate Resistant Prostate Cancer (CRPC and subsequent metastasis lead to poor survival outcome, suggesting that there is a dire need for novel mechanistic understanding of tumor recurrence, which would be critical for designing novel therapies. The recurrence and the metastasis of PCa are tightly linked with the biology of prostate cancer stem cells or cancer-initiating cells that is reminiscent of the acquisition of Epithelial to Mesenchymal Transition (EMT phenotype. Increasing evidence suggests that EMT-type cells share many biological characteristics with cancer stem-like cells. METHODOLOGY/PRINCIPAL FINDINGS: In this study, we found that PCa cells with EMT phenotype displayed stem-like cell features characterized by increased expression of Sox2, Nanog, Oct4, Lin28B and/or Notch1, consistent with enhanced clonogenic and sphere (prostasphere-forming ability and tumorigenecity in mice, which was associated with decreased expression of miR-200 and/or let-7 family. Reversal of EMT by re-expression of miR-200 inhibited prostasphere-forming ability of EMT-type cells and reduced the expression of Notch1 and Lin28B. Down-regulation of Lin28B increased let-7 expression, which was consistent with repressed self-renewal capability. CONCLUSIONS/SIGNIFICANCE: These results suggest that miR-200 played a pivotal role in linking the characteristics of cancer stem-like cells with EMT-like cell signatures in PCa. Selective elimination of cancer stem-like cells by reversing the EMT phenotype to Mesenchymal-Epithelial Transition (MET phenotype using novel agents would be useful for the prevention of tumor recurrence especially by eliminating those cells that are the "Root Cause" of tumor development and recurrence.

  15. Biological Effects of Green Tea Capsule Supplementation in Pre-surgery Postmenopausal Breast Cancer Patients

    Directory of Open Access Journals (Sweden)

    Steven S Yu


    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.

  16. Targeting Strategies for Renal Cell Carcinoma: From Renal Cancer Cells to Renal Cancer Stem Cells


    Yuan, Zhi-xiang; Mo, Jingxin; Zhao, Guixian; Shu, Gang; Fu, Hua-Lin; Wei ZHAO


    Renal cell carcinoma (RCC) is a common form of urologic tumor that originates from the highly heterogeneous epithelium of renal tubules. Over the last decade, targeting therapies to renal cancer cells have transformed clinical care for RCC. Recently, it was proposed that renal cancer stem cells (CSCs) isolated from renal carcinomas were responsible for driving tumor growth and resistance to conventional chemotherapy and radiotherapy, according to the theory of CSCs; this has provided the rati...

  17. Using stem cell biology to study and treat ophthalmologic and oculoplastic diseases. (United States)

    Wu, Albert Y; Daniel, Michael G


    With the rapid growth of the stem cell biology field, the prospect of regenerative medicine across multiple tissue types comes closer to reality. Several groundbreaking steps paved the way for applying stem cell biology to the several subfields within ophthalmology and oculoplastic surgery. These steps include the use of stem cell transplants as well as studies of various ophthalmologic pathologies at the molecular level. The necessity of stem cell transplant is readily apparent, having already been used for several studies such as artificial lacrimal gland design and eyelid reconstruction. Investigating the stem cell biology behind oncological diseases of the eye has also developed recently, such as with the identification of specific markers to label cancer stem cells in orbital adenoid cystic carcinoma. The advent of induced pluripotent stem cells led to a burst of productivity in the field of regenerative medicine, making it possible to take a patient's own cells, reprogram them, and use them to either study patient-specific pathology in vitro or use them for eventual patient specific therapeutics. Patient-specific adipose-derived stem cells (ASCs) have been used for a variety of treatments, such as wound healing and burn therapies. As the fields of stem cell biology and regenerative medicine continue to progress, its use will become a mainstay of patient-specific cell therapies in the future.

  18. A Diagnostic Assessment for Introductory Molecular and Cell Biology (United States)

    Shi, Jia; Wood, William B.; Martin, Jennifer M.; Guild, Nancy A.; Vicens, Quentin; Knight, Jennifer K.


    We have developed and validated a tool for assessing understanding of a selection of fundamental concepts and basic knowledge in undergraduate introductory molecular and cell biology, focusing on areas in which students often have misconceptions. This multiple-choice Introductory Molecular and Cell Biology Assessment (IMCA) instrument is designed…

  19. Cell Biology and Microbiology: A Continuous Cross-Feeding. (United States)

    Pizarro-Cerdá, Javier; Cossart, Pascale


    Microbiology and cell biology both involve the study of cells, albeit at different levels of complexity and scale. Interactions between both fields during the past 25 years have led to major conceptual and technological advances that have reshaped the whole biology landscape and its biomedical applications. Copyright © 2016 Elsevier Ltd. All rights reserved.

  20. Alternative Educational Approach to Introducing Cell Biology

    Directory of Open Access Journals (Sweden)

    Rosilane T. Silva


    Full Text Available First year medical students usually have a great  difficulty to visualize a three  dimensional  cell. They also present a series of misconceptions  related to cell biology that seems to begin in the high school. An alternative educational approach  is being tested  with high school students in order to minimize these misconceptions,  and also increase the pupils interest in the subject.  The approach  combines theoretical classes with experimental activities, the  use of models, games, discussions,  and oral presentations by the students at the end of the educational module.  In short,  the experimental activities  are low-cost, easy-to-follow experiments that basically show a few properties  of the living cells, such as membrane transport, enzyme action  as well as the  importance of the  membrane  integrity for life.  A card  game relates  the  functions  of the organnels  by matching  pairs  of cards.  This  game has one card without a matching  pair  that explains  apoptosis;  the  player  that ends up with  this  card  loses the game.   The pupils learn while they play the game.  A 3D model of the membrane  shows the major components  and allows the observation of membrane  assimetry.   After comparing  some panels of photomicrographs of cells and organnels, the students are presented  to a 3D model of a cell as the teacher  tries to relate the panels  with  a three  dimensional  visualization.  They  also have the  opportunity to present their  own models.  The opinion of high school teachers  about  the different activities  will be shown.  The aim of this educational module is to promote  learning while different abilities, according to Gardners  Multiple Intelligences  Theory,  such as the visual-spatial, bodily-kinesthetic, interpersonal, and naturalistic are being developed.  We believe that the diversity  of approaches  is one of the most important

  1. Nest expansion assay: a cancer systems biology approach to in vitro invasion measurements

    Directory of Open Access Journals (Sweden)

    Estrada Lourdes


    contributing to cancer cell invasion, particularly suitable for parameterizing and validating Cancer Systems Biology approaches such as mathematical modeling.

  2. Proteomic alterations of fibroblasts induced by ovarian cancer cells reveal potential cancer targets. (United States)

    Zhang, X Y; Hong, S S; Zhang, M; Cai, Q Q; Zhang, M X; Xu, C J


    The common spread pattern of ovarian cancer is peritoneal implantation. The growth of the shed ovarian cancer cells in the peritoneal cavity is closely related to the tumor microenvironment. Cancer-associated fibroblasts are vital in the tumor microenvironment. It is not clearly defined that the protein expression alters during the activating process of fibroblasts. This study detected the protein alterations in fibroblasts induced by ovarian cancer cells and explored the potential biological relevance through two-dimensional gel electrophoresis and mass spectrometry. Our data showed that the level of CENPE, BAG2, SOD2, GDI2, CORO1C, CFL1, DSTN, CALD1, PHGDH, PDHA1, AKR1B1, TST and TBCA proteins were significantly up-regulated in the fibroblasts co-cultured with ovarian cancer cells, whereas HSPB1, P4HB and VIM were significantly down-regulated. However, only BAG2, SOD2 and CORO1C proteins were confirmed to be significantly increased by western blot analysis. The differentially expressed proteins were mainly involved in metabolic processes, cellular component organization, responses to stimulus, multicellular organismal processes, localization, protein depolymerization, cellular senescence and the mitotic pathway. These data demonstrated that fibroblasts had an altered protein expression pattern after being induced by ovarian cancer cells, and participated in multiple cell processes resulting in tumor progression. The differentially expressed proteins should be considered as targets for cancer treatment Keywords: ovarian neoplasms, fibroblast, stroma, biomarker, proteomics.

  3. Industrial systems biology and its impact on synthetic biology of yeast cell factories. (United States)

    Fletcher, Eugene; Krivoruchko, Anastasia; Nielsen, Jens


    Engineering industrial cell factories to effectively yield a desired product while dealing with industrially relevant stresses is usually the most challenging step in the development of industrial production of chemicals using microbial fermentation processes. Using synthetic biology tools, microbial cell factories such as Saccharomyces cerevisiae can be engineered to express synthetic pathways for the production of fuels, biopharmaceuticals, fragrances, and food flavors. However, directing fluxes through these synthetic pathways towards the desired product can be demanding due to complex regulation or poor gene expression. Systems biology, which applies computational tools and mathematical modeling to understand complex biological networks, can be used to guide synthetic biology design. Here, we present our perspective on how systems biology can impact synthetic biology towards the goal of developing improved yeast cell factories. Biotechnol. Bioeng. 2016;113: 1164-1170. © 2015 Wiley Periodicals, Inc. © 2015 Wiley Periodicals, Inc.

  4. A data integration approach for cell cycle analysis oriented to model simulation in systems biology

    Directory of Open Access Journals (Sweden)

    Mosca Ettore


    Full Text Available Abstract Background The cell cycle is one of the biological processes most frequently investigated in systems biology studies and it involves the knowledge of a large number of genes and networks of protein interactions. A deep knowledge of the molecular aspect of this biological process can contribute to making cancer research more accurate and innovative. In this context the mathematical modelling of the cell cycle has a relevant role to quantify the behaviour of each component of the systems. The mathematical modelling of a biological process such as the cell cycle allows a systemic description that helps to highlight some features such as emergent properties which could be hidden when the analysis is performed only from a reductionism point of view. Moreover, in modelling complex systems, a complete annotation of all the components is equally important to understand the interaction mechanism inside the network: for this reason data integration of the model components has high relevance in systems biology studies. Description In this work, we present a resource, the Cell Cycle Database, intended to support systems biology analysis on the Cell Cycle process, based on two organisms, yeast and mammalian. The database integrates information about genes and proteins involved in the cell cycle process, stores complete models of the interaction networks and allows the mathematical simulation over time of the quantitative behaviour of each component. To accomplish this task, we developed, a web interface for browsing information related to cell cycle genes, proteins and mathematical models. In this framework, we have implemented a pipeline which allows users to deal with the mathematical part of the models, in order to solve, using different variables, the ordinary differential equation systems that describe the biological process. Conclusion This integrated system is freely available in order to support systems biology research on the cell cycle and

  5. Accelerating cancer systems biology research through Semantic Web technology. (United States)

    Wang, Zhihui; Sagotsky, Jonathan; Taylor, Thomas; Shironoshita, Patrick; Deisboeck, Thomas S


    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. Copyright © 2012 Wiley Periodicals, Inc.

  6. Cell Culture in Microgravity: Opening the Door to Space Cell Biology (United States)

    Pellis, Neal R.; Dawson, David L. (Technical Monitor)


    Adaptational response of human cell populations to microgravity is investigated using simulation, short-term Shuttle experiments, and long-term microgravity. Simulation consists of a clinostatically-rotated cell culture system. The system is a horizontally-rotated cylinder completely filled with culture medium. Low speed rotation results in continuous-fall of the cells through the fluid medium. In this setting, cells: 1) aggregate, 2) propagate in three dimensions, 3) synthesize matrix, 4) differentiate, and 5) form sinusoids that facilitate mass transfer. Space cell culture is conducted in flight bioreactors and in static incubators. Cells grown in microgravity are: bovine cartilage, promyelocytic leukemia, kidney proximal tubule cells, adrenal medulla, breast and colon cancer, and endothelium. Cells were cultured in space to test specific hypotheses. Cartilage cells were used to determine structural differences in cartilage grown in space compared to ground-based bioreactors. Results from a 130-day experiment on Mir revealed that cartilage grown in space was substantially more compressible due to insufficient glycosaminoglycan in the matrix. Interestingly, earth-grown cartilage conformed better to the dimensions of the scaffolding material, while the Mir specimens were spherical. The other cell populations are currently being analyzed for cell surface properties, gene expression, and differentiation. Results suggest that some cells spontaneously differentiate in microgravity. Additionally, vast changes in gene expression may occur in response to microgravity. In conclusion, the transition to microgravity may constitute a physical perturbation in cells resulting in unique gene expressions, the consequences of which may be useful in tissue engineering, disease modeling, and space cell biology.

  7. Biological processes, properties and molecular wiring diagrams of candidate low-penetrance breast cancer susceptibility genes

    Directory of Open Access Journals (Sweden)

    Moreno Víctor


    Full Text Available Abstract Background Recent advances in whole-genome association studies (WGASs for human cancer risk are beginning to provide the part lists of low-penetrance susceptibility genes. However, statistical analysis in these studies is complicated by the vast number of genetic variants examined and the weak effects observed, as a result of which constraints must be incorporated into the study design and analytical approach. In this scenario, biological attributes beyond the adjusted statistics generally receive little attention and, more importantly, the fundamental biological characteristics of low-penetrance susceptibility genes have yet to be determined. Methods We applied an integrative approach for identifying candidate low-penetrance breast cancer susceptibility genes, their characteristics and molecular networks through the analysis of diverse sources of biological evidence. Results First, examination of the distribution of Gene Ontology terms in ordered WGAS results identified asymmetrical distribution of Cell Communication and Cell Death processes linked to risk. Second, analysis of 11 different types of molecular or functional relationships in genomic and proteomic data sets defined the "omic" properties of candidate genes: i/ differential expression in tumors relative to normal tissue; ii/ somatic genomic copy number changes correlating with gene expression levels; iii/ differentially expressed across age at diagnosis; and iv/ expression changes after BRCA1 perturbation. Finally, network modeling of the effects of variants on germline gene expression showed higher connectivity than expected by chance between novel candidates and with known susceptibility genes, which supports functional relationships and provides mechanistic hypotheses of risk. Conclusion This study proposes that cell communication and cell death are major biological processes perturbed in risk of breast cancer conferred by low-penetrance variants, and defines the common

  8. Biological processes, properties and molecular wiring diagrams of candidate low-penetrance breast cancer susceptibility genes. (United States)

    Bonifaci, Núria; Berenguer, Antoni; Díez, Javier; Reina, Oscar; Medina, Ignacio; Dopazo, Joaquín; Moreno, Víctor; Pujana, Miguel Angel


    Recent advances in whole-genome association studies (WGASs) for human cancer risk are beginning to provide the part lists of low-penetrance susceptibility genes. However, statistical analysis in these studies is complicated by the vast number of genetic variants examined and the weak effects observed, as a result of which constraints must be incorporated into the study design and analytical approach. In this scenario, biological attributes beyond the adjusted statistics generally receive little attention and, more importantly, the fundamental biological characteristics of low-penetrance susceptibility genes have yet to be determined. We applied an integrative approach for identifying candidate low-penetrance breast cancer susceptibility genes, their characteristics and molecular networks through the analysis of diverse sources of biological evidence. First, examination of the distribution of Gene Ontology terms in ordered WGAS results identified asymmetrical distribution of Cell Communication and Cell Death processes linked to risk. Second, analysis of 11 different types of molecular or functional relationships in genomic and proteomic data sets defined the "omic" properties of candidate genes: i/ differential expression in tumors relative to normal tissue; ii/ somatic genomic copy number changes correlating with gene expression levels; iii/ differentially expressed across age at diagnosis; and iv/ expression changes after BRCA1 perturbation. Finally, network modeling of the effects of variants on germline gene expression showed higher connectivity than expected by chance between novel candidates and with known susceptibility genes, which supports functional relationships and provides mechanistic hypotheses of risk. This study proposes that cell communication and cell death are major biological processes perturbed in risk of breast cancer conferred by low-penetrance variants, and defines the common omic properties, molecular interactions and possible functional

  9. Mast Cells as a Potential Prognostic Marker in Prostate Cancer

    Directory of Open Access Journals (Sweden)

    Gianluigi Taverna


    Full Text Available Despite years of intensive investigation that has been made in understanding prostate cancer, it remains one of the major men’s health issues and the leading cause of death worldwide. It is now ascertained that prostate cancer emerges from multiple spontaneous and/or inherited alterations that induce changes in expression patterns of genes and proteins that function in complex networks controlling critical cellular events. It is now accepted that several innate and adaptive immune cells, including T- and B-lymphocytes, macrophages, natural killer cells, dendritic cells, neutrophils, eosinophils, and mast cells (MCs, infiltrate the prostate cancer. All of these cells are irregularly scattered within the tumor and loaded with an assorted array of cytokines, chemokines, and inflammatory and cytotoxic mediators. This complex framework reflects the diversity in tumor biology and tumor-host interactions. MCs are well-established effector cells in Immunoglobulin-E (Ig-E associated immune responses and potent effector cells of the innate immune system; however, their clinical significance in prostate cancer is still debated. Here, these controversies are summarized, focusing on the implications of these findings in understanding the roles of MCs in primary prostate cancer.

  10. A Review of Cell Adhesion Studies for Biomedical and Biological Applications (United States)

    Ahmad Khalili, Amelia; Ahmad, Mohd Ridzuan


    Cell adhesion is essential in cell communication and regulation, and is of fundamental importance in the development and maintenance of tissues. The mechanical interactions between a cell and its extracellular matrix (ECM) can influence and control cell behavior and function. The essential function of cell adhesion has created tremendous interests in developing methods for measuring and studying cell adhesion properties. The study of cell adhesion could be categorized into cell adhesion attachment and detachment events. The study of cell adhesion has been widely explored via both events for many important purposes in cellular biology, biomedical, and engineering fields. Cell adhesion attachment and detachment events could be further grouped into the cell population and single cell approach. Various techniques to measure cell adhesion have been applied to many fields of study in order to gain understanding of cell signaling pathways, biomaterial studies for implantable sensors, artificial bone and tooth replacement, the development of tissue-on-a-chip and organ-on-a-chip in tissue engineering, the effects of biochemical treatments and environmental stimuli to the cell adhesion, the potential of drug treatments, cancer metastasis study, and the determination of the adhesion properties of normal and cancerous cells. This review discussed the overview of the available methods to study cell adhesion through attachment and detachment events. PMID:26251901

  11. MET and Small-Cell Lung Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Gelsomino, Francesco, E-mail: [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)


    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.

  12. MET and Small-Cell Lung Cancer

    Directory of Open Access Journals (Sweden)

    Francesco Gelsomino


    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.

  13. 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: [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)


    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. Synthetic Biology: A Bridge between Artificial and Natural Cells. (United States)

    Ding, Yunfeng; Wu, Fan; Tan, Cheemeng


    Artificial cells are simple cell-like entities that possess certain properties of natural cells. In general, artificial cells are constructed using three parts: (1) biological membranes that serve as protective barriers, while allowing communication between the cells and the environment; (2) transcription and translation machinery that synthesize proteins based on genetic sequences; and (3) genetic modules that control the dynamics of the whole cell. Artificial cells are minimal and well-defined systems that can be more easily engineered and controlled when compared to natural cells. Artificial cells can be used as biomimetic systems to study and understand natural dynamics of cells with minimal interference from cellular complexity. However, there remain significant gaps between artificial and natural cells. How much information can we encode into artificial cells? What is the minimal number of factors that are necessary to achieve robust functioning of artificial cells? Can artificial cells communicate with their environments efficiently? Can artificial cells replicate, divide or even evolve? Here, we review synthetic biological methods that could shrink the gaps between artificial and natural cells. The closure of these gaps will lead to advancement in synthetic biology, cellular biology and biomedical applications.

  15. Method for separating biological cells. [suspended in aqueous polymer systems (United States)

    Brooks, D. E. (Inventor)


    A method for separating biological cells by suspending a mixed cell population in a two-phase polymer system is described. The polymer system consists of droplet phases with different surface potentials for which the cell populations exhibit different affinities. The system is subjected to an electrostatic field of sufficient intensity to cause migration of the droplets with an attendant separation of cells.

  16. Troglitazone reverses the multiple drug resistance phenotype in cancer cells

    Directory of Open Access Journals (Sweden)

    Gerald F Davies


    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

  17. Radiofrequency treatment alters cancer cell phenotype (United States)

    Ware, Matthew J.; Tinger, Sophia; Colbert, Kevin L.; Corr, Stuart J.; Rees, Paul; Koshkina, Nadezhda; Curley, Steven; Summers, H. D.; Godin, Biana


    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.

  18. Ovarian Cancer Stem Cells: A New Target for Cancer Therapy

    Directory of Open Access Journals (Sweden)

    Qinglei Zhan


    Full Text Available Ovarian cancer is a highly lethal disease among all gynecologic malignancies and is the fifth leading cause of cancer-related death in women. Although the standard combination of surgery and chemotherapy was initially effective in patients with ovarian cancer, disease relapse commonly occurred due to the generation of chemoresistance. It has been reported that cancer stem cells (CSCs are involved in drug resistance and cancer recurrence. Over the past decades, increasing studies have been done to identify CSCs from human ovarian cancer cells. The present paper will summarize different investigations on ovarian CSCs, including isolation, mechanisms of chemoresistance, and therapeutic approaches. Although there are still numerous challenges to translate basic research to clinical applications, understanding the molecular details of CSCs is essential for developing effective strategies to prevent ovarian cancer and its recurrence.

  19. Learning Cell Biology as a Team: A Project-Based Approach to Upper-Division Cell Biology (United States)

    Wright, Robin; Boggs, James


    To help students develop successful strategies for learning how to learn and communicate complex information in cell biology, we developed a quarter-long cell biology class based on team projects. Each team researches a particular human disease and presents information about the cellular structure or process affected by the disease, the cellular…

  20. Cancer stem cell targeted therapy: progress amid controversies (United States)

    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


    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 illustrated and via providing a panoramic view of cancer therapy, we addressed the recent controversies regarding the feasibility of cancer stem cells targeted anti-cancer therapy. PMID:26496035

  1. Stages of Small Cell Lung Cancer (United States)

    ... inside of the lungs. Enlarge Anatomy of the respiratory system, showing the trachea and both lungs and their ... Cell Lung Cancer Tobacco (includes help with quitting) Cigarette Smoking: Health Risks and How to Quit Secondhand Smoke and Cancer For general cancer information and other ...

  2. Treatment Option Overview (Small Cell Lung Cancer) (United States)

    ... inside of the lungs. Enlarge Anatomy of the respiratory system, showing the trachea and both lungs and their ... Cell Lung Cancer Tobacco (includes help with quitting) Cigarette Smoking: Health Risks and How to Quit Secondhand Smoke and Cancer For general cancer information and other ...

  3. General Information about Small Cell Lung Cancer (United States)

    ... inside of the lungs. Enlarge Anatomy of the respiratory system, showing the trachea and both lungs and their ... Cell Lung Cancer Tobacco (includes help with quitting) Cigarette Smoking: Health Risks and How to Quit Secondhand Smoke and Cancer For general cancer information and other ...

  4. Cancer stem cells of the digestive system. (United States)

    Colvin, Hugh S; Nishida, Naohiro; Koseki, Jun; Konno, Masamitsu; Kawamoto, Koichi; Tsunekuni, Kenta; Doki, Yuichiro; Mori, Masaki; Ishii, Hideshi


    Stem cells of the digestive system are ideal in many ways for research, given they are abundant, highly proliferative and have a uniform structural arrangement. This in turn has enormously aided the research of cancer stem cells of the digestive system, which is now shaping our understanding of cancer stem cells. In this review, the recent advances in the understanding of cancer stem cells of the digestive system have been summarized, including aspects such as their identification, origin, cell-cycle dormancy, relationship with epithelial-mesenchymal transition, cellular metabolism and the underlying molecular mechanisms. Newly acquired knowledge concerning cancer stem cells have led to the development of novel cancer therapeutics with provisional yet encouraging results. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please email:

  5. Cancer Stem Cells: Repair Gone Awry?

    Directory of Open Access Journals (Sweden)

    Fatima Rangwala


    Full Text Available Because cell turnover occurs in all adult organs, stem/progenitor cells within the stem-cell niche of each tissue must be appropriately mobilized and differentiated to maintain normal organ structure and function. Tissue injury increases the demands on this process, and thus may unmask defective regulation of pathways, such as Hedgehog (Hh, that modulate progenitor cell fate. Hh pathway dysregulation has been demonstrated in many types of cancer, including pancreatic and liver cancers, in which defective Hh signaling has been linked to outgrowth of Hh-responsive cancer stem-initiating cells and stromal elements. Hence, the Hh pathway might be a therapeutic target in such tumors.

  6. The biology of innate lymphoid cells

    NARCIS (Netherlands)

    Artis, David; Spits, Hergen


    The innate immune system is composed of a diverse array of evolutionarily ancient haematopoietic cell types, including dendritic cells, monocytes, macrophages and granulocytes. These cell populations collaborate with each other, with the adaptive immune system and with non-haematopoietic cells to

  7. Preface of the "Symposium on Mathematical Models and Methods to investigate Heterogeneity in Cell and Cell Population Biology" (United States)

    Clairambault, Jean


    This session investigates hot topics related to mathematical representations of cell and cell population dynamics in biology and medicine, in particular, but not only, with applications to cancer. Methods in mathematical modelling and analysis, and in statistical inference using single-cell and cell population data, should contribute to focus this session on heterogeneity in cell populations. Among other methods are proposed: a) Intracellular protein dynamics and gene regulatory networks using ordinary/partial/delay differential equations (ODEs, PDEs, DDEs); b) Representation of cell population dynamics using agent-based models (ABMs) and/or PDEs; c) Hybrid models and multiscale models to integrate single-cell dynamics into cell population behaviour; d) Structured cell population dynamics and asymptotic evolution w.r.t. relevant traits; e) Heterogeneity in cancer cell populations: origin, evolution, phylogeny and methods of reconstruction; f) Drug resistance as an evolutionary phenotype: predicting and overcoming it in therapeutics; g) Theoretical therapeutic optimisation of combined drug treatments in cancer cell populations and in populations of other organisms, such as bacteria.

  8. Biology of breast cancer during pregnancy using genomic profiling. (United States)

    Azim, Hatem A; Brohée, Sylvain; Peccatori, Fedro A; Desmedt, Christine; Loi, Sherene; Lambrechts, Diether; Dell'Orto, Patrizia; Majjaj, Samira; Jose, Vinu; Rotmensz, Nicole; Ignatiadis, Michail; Pruneri, Giancarlo; Piccart, Martine; Viale, Giuseppe; Sotiriou, Christos


    Breast cancer during pregnancy is rare and is associated with relatively poor prognosis. No information is available on its biological features at the genomic level. Using a dataset of 54 pregnant and 113 non-pregnant breast cancer patients, we evaluated the pattern of hot spot somatic mutations and did transcriptomic profiling using Sequenom and Affymetrix respectively. We performed gene set enrichment analysis to evaluate the pathways associated with diagnosis during pregnancy. We also evaluated the expression of selected cancer-related genes in pregnant and non-pregnant patients and correlated the results with changes occurring in the normal breast using a pregnant murine model. We finally investigated aberrations associated with disease-free survival (DFS). No significant differences in mutations were observed. Of the total number of patients, 18.6% of pregnant and 23% of non-pregnant patients had a PIK3CA mutation. Around 30% of tumors were basal, with no differences in the distribution of breast cancer molecular subtypes between pregnant and non-pregnant patients. Two pathways were enriched in tumors diagnosed during pregnancy: the G protein-coupled receptor pathway and the serotonin receptor pathway (FDR pregnancy had higher expression of PD1 (PDCD1; P=0.015), PDL1 (CD274; P=0.014), and gene sets related to SRC (P=0.004), IGF1 (P=0.032), and β-catenin (P=0.019). Their expression increased almost linearly throughout gestation when evaluated on the normal breast using a pregnant mouse model underscoring the potential effect of the breast microenvironment on tumor phenotype. No genes were associated with DFS in a multivariate model, which could be due to low statistical power. Diagnosis during pregnancy impacts the breast cancer transcriptome including potential cancer targets. © 2014 Society for Endocrinology.

  9. A triterpenoid from wild bitter gourd inhibits breast cancer cells (United States)

    Bai, Li-Yuan; Chiu, Chang-Fang; Chu, Po-Chen; Lin, Wei-Yu; Chiu, Shih-Jiuan; Weng, Jing-Ru


    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.

  10. Metabolomics Analyses of Cancer Cells in Controlled Microenvironments. (United States)

    Gravel, Simon-Pierre; Avizonis, Daina; St-Pierre, Julie


    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.

  11. 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: [Department of Molecular Pharmacology and Therapeutics, Loyola University Chicago 2160 S. 1st Ave, Maywood, IL 60153 (United States)


    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.

  12. Modeling cell-in-cell structure into its biological significance


    He, M-f; Wang, S; Wang, Y.; Wang, X-n


    Although cell-in-cell structure was noted 100 years ago, the molecular mechanisms of ?entering' and the destination of cell-in-cell remain largely unclear. It takes place among the same type of cells (homotypic cell-in-cell) or different types of cells (heterotypic cell-in-cell). Cell-in-cell formation affects both effector cells and their host cells in multiple aspects, while cell-in-cell death is under more intensive investigation. Given that cell-in-cell has an important role in maintainin...

  13. MCF-10A-NeoST: A New Cell System for Studying Cell-ECM and Cell-Cell Interactions in Breast Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Zantek, Nicole Dodge; Walker-Daniels, Jennifer; Stewart, Jane; Hansen, Rhonda K.; Robinson, Daniel; Miao, Hui; Wang, Bingcheng; Kung, Hsing-Jien; Bissell, Mina J.; Kinch, Michael S.


    There is a continuing need for genetically matched cell systems to model cellular behaviors that are frequently observed in aggressive breast cancers. We report here the isolation and initial characterization of a spontaneously arising variant of MCF-10A cells, NeoST, which provides a new model to study cell adhesion and signal transduction in breast cancer. NeoST cells recapitulate important biological and biochemical features of metastatic breast cancer, including anchorage-independent growth, invasiveness in threedimensional reconstituted membranes, loss of E-cadherin expression, and increased tyrosine kinase activity. A comprehensive analysis of tyrosine kinase expression revealed overexpression or functional activation of the Axl, FAK, and EphA2 tyrosine kinases in transformed MCF-10A cells. MCF-10A and these new derivatives provide a genetically matched model to study defects in cell adhesion and signaling that are relevant to cellular behaviors that often typify aggressive breast cancer cells.

  14. Human colon cancer HT-29 cell death responses to doxorubicin and Morus Alba leaves flavonoid extract. (United States)

    Fallah, S; Karimi, A; Panahi, G; Gerayesh Nejad, S; Fadaei, R; Seifi, M


    The mechanistic basis for the biological properties of Morus alba flavonoid extract (MFE) and chemotherapy drug of doxorubicin on human colon cancer HT-29 cell line death are unknown. The effect of doxorubicin and flavonoid extract on colon cancer HT-29 cell line death and identification of APC gene expression and PARP concentration of HT-29 cell line were investigated. The results showed that flavonoid extract and doxorubicin induce a dose dependent cell death in HT-29 cell line. MFE and doxorubicin exert a cytotoxic effect on human colon cancer HT-29 cell line by probably promoting or induction of apoptosis.

  15. NK Cells and Virus-Related Cancers


    Mishra, Rabinarayan; Welsh, Raymond M.; Szomolanyi-Tsuda, Eva


    Natural killer (NK) cells become activated during viral infections and can play roles in such infections by attacking virus-infected cells or by regulating adaptive immune responses. Experimental models suggest that NK cells may also have the capacity to restrain virus-induced cancers. Here, we discuss the seven viruses linked to human cancers and the evidence of NK cell involvement in these systems.

  16. Road for understanding cancer stem cells

    DEFF Research Database (Denmark)

    Serakinci, Nedime; Erzik, Can


    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 ......, help us both in the identification and characterization of cancer stem cells and in the further development of therapeutic strategies including tissue engineering...

  17. Carbon Nanotubes: An Emerging Drug Carrier for Targeting Cancer Cells (United States)

    Bhattacharya, Shiv Sankar; Mishra, Arun Kumar; Verma, Navneet; Verma, Anurag; Pandit, Jayanta Kumar


    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

  18. Carbon Nanotubes: An Emerging Drug Carrier for Targeting Cancer Cells

    Directory of Open Access Journals (Sweden)

    Vaibhav Rastogi


    Full Text Available 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.

  19. Industrial systems biology and its impact on synthetic biology of yeast cell factories

    DEFF Research Database (Denmark)

    Fletcher, Eugene; Krivoruchko, Anastasia; Nielsen, Jens


    Engineering industrial cell factories to effectively yield a desired product while dealing with industrially relevant stresses is usually the most challenging step in the development of industrial production of chemicals using microbial fermentation processes. Using synthetic biology tools......, microbial cell factories such as Saccharomyces cerevisiae can be engineered to express synthetic pathways for the production of fuels, biopharmaceuticals, fragrances, and food flavors. However, directing fluxes through these synthetic pathways towards the desired product can be demanding due to complex...... regulation or poor gene expression. Systems biology, which applies computational tools and mathematical modeling to understand complex biological networks, can be used to guide synthetic biology design. Here, we present our perspective on how systems biology can impact synthetic biology towards the goal...

  20. Targeting the osteosarcoma cancer stem cell

    Directory of Open Access Journals (Sweden)

    Qin Ling


    Full Text Available Abstract Osteosarcoma is the most common type of solid bone cancer and the second leading cause of cancer-related death in pediatric patients. Many patients are not cured by the current osteosarcoma therapy consisting of combination chemotherapy along with surgery and thus new treatments are urgently needed. In the last decade, cancer stem cells have been identified in many tumors such as leukemia, brain, breast, head and neck, colon, skin, pancreatic, and prostate cancers and these cells are proposed to play major roles in drug resistance, tumor recurrence, and metastasis. Recent studies have shown evidence that osteosarcoma also possesses cancer stem cells. This review summarizes the current knowledge about the osteosarcoma cancer stem cell including the methods used for its isolation, its properties, and its potential as a new target for osteosarcoma treatment.

  1. The biology and function of exosomes in cancer (United States)

    Kalluri, Raghu


    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

  2. Extracellular Molecules Involved in Cancer Cell Invasion

    Energy Technology Data Exchange (ETDEWEB)

    Stivarou, Theodora; Patsavoudi, Evangelia, E-mail: [Department of Biochemistry, Hellenic Pasteur Institute, Athens 11521 (Greece); Technological Educational Institute of Athens, Egaleo, Athens 12210 (Greece)


    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.

  3. Dissecting Social Cell Biology and Tumors Using Drosophila Genetics


    Pastor-Pareja, José Carlos; Xu, Tian


    Cancer was seen for a long time as a strictly cell-autonomous process in which oncogenes and tumor-suppressor mutations drive clonal cell expansions. Research in the past decade, however, paints a more integrative picture of communication and interplay between neighboring cells in tissues. It is increasingly clear as well that tumors, far from being homogenous lumps of cells, consist of different cell types that function together as complex tissue-level communities. The repertoire of interact...

  4. Does rarity mean imparity? Biological characteristics of osteosarcoma cells originating from the spine. (United States)

    Zhou, Zhenhua; Li, Yan; Yan, Xu; Wang, Xudong; Yang, Cheng; Wei, Haifeng; Yang, Xinghai; Xiao, Jianru


    Osteosarcoma is one of the most common malignancies in bones and is often found in limbs. Until now, it is not clear why osteosarcoma is rare in the spine. On the other hand, previous biological characteristics study about osteosarcoma of spine was also rare because of its low incidence. To explore the biology of spinal osteosarcoma, a stable osteosarcoma cell line derived from spine is necessary. A novel osteosarcoma cell line named NEO217 was established from spinal osteosarcoma tissues obtained from a Chinese male patient. We performed a series of experiments to investigate the biological properties of NEO217, including cell morphology, the kinetics of cell growth, biomarkers and tumorigenicity. The cell line NEO217 was passaged in vitro for more than 50 generations. Ultramicroscopic structural features of these cells were consistent with the pleomorphism characteristic of cancer cells. The average cell doubling time was 26 h. The chromosomal morphology was that of a human karyotype, with the number of chromosomes more than 80. NEO217 cells and available osteosarcoma cell lines such as MG-63 and MNNG/HOS were all CD29+CD59+ phenotype as detected by flow cytometry. Inoculation of NEO217 cells to immunodeficient mice led to tumor formation. The biological and molecular properties of NEO217 cell line are not exactly the same as some human osteosarcoma cell lines derived from the extremities. We have established a novel osteosarcoma cell line NEO217 derived from the spine, which will provide a useful model for biological or therapeutical studies of spinal osteosarcoma.

  5. Breast Cancer-Initiating Cells: Insights into Novel Treatment Strategies

    Directory of Open Access Journals (Sweden)

    Maria Grazia Daidone


    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.

  6. Cell of Origin and Cancer Stem Cell Phenotype in Medulloblastomas (United States)


    dominant role over some oncogene function.In addition, we recently reported that cancer stem cells (CSCs)- stem cell like cells in tumors that have stem ... cell properties and tumor initiating ability- retain epigenetic memories of their cells of origin (Chow et al., 2014). We showed that CSCs derived from

  7. Bridging cancer biology and the patients' needs with nanotechnology-based approaches. (United States)

    Fonseca, Nuno A; Gregório, Ana C; Valério-Fernandes, Angela; Simões, Sérgio; Moreira, João N


    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. Copyright © 2014 Elsevier Ltd. All rights reserved.

  8. Targeting senescence cells in pancreatic cancer | IDRC ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    Targeting senescence cells in pancreatic cancer. Cellular senescence is a programmed response to oncogenic (tumour-causing) stress that aims to halt the expansion of cells with malignant potential. It does this by stopping the proliferation of pre-cancerous lesions and recruitment of the immune system for their elimination.

  9. Betulinic Acid Kills Colon Cancer Stem Cells

    NARCIS (Netherlands)

    Potze, Lisette; Di Franco, Simone; Kessler, Jan H.; Stassi, Giorgio; Medema, Jan Paul


    Cancer stem cells (CSCs) are considered to be the origin of cancer and it is suggested that they are resistant to chemotherapy. Current therapies fail to eradicate CSCs and therefore selecting a resistant cell subset that is able to facilitate tumor recurrences. Betulinic acid (BetA) is a broad

  10. Embryonic stem cell biology: insights from molecular imaging. (United States)

    Sallam, Karim; Wu, Joseph C


    Embryonic stem (ES) cells have therapeutic potential in disorders of cellular loss such as myocardial infarction, type I diabetes and neurodegenerative disorders. ES cell biology in living subjects was largely poorly understood until incorporation of molecular imaging into the field. Reporter gene imaging works by integrating a reporter gene into ES cells and using a reporter probe to induce a signal detectable by normal imaging modalities. Reporter gene imaging allows for longitudinal tracking of ES cells within the same host for a prolonged period of time. This has advantages over postmortem immunohistochemistry and traditional imaging modalities. The advantages include expression of reporter gene is limited to viable cells, expression is conserved between generations of dividing cells, and expression can be linked to a specific population of cells. These advantages were especially useful in studying a dynamic cell population such as ES cells and proved useful in elucidating the biology of ES cells. Reporter gene imaging identified poor integration of differentiated ES cells transplanted into host tissue as well as delayed donor cell death as reasons for poor long-term survival in vivo. This imaging technology also confirmed that ES cells indeed have immunogenic properties that factor into cell survival and differentiation. Finally, reporter gene imaging improved our understanding of the neoplastic risk of undifferentiated ES cells in forming teratomas. Despite such advances, much remains to be understood about ES cell biology to translate this technology to the bedside, and reporter gene imaging will certainly play a key role in formulating this understanding.

  11. Cell-free synthetic biology for environmental sensing and remediation. (United States)

    Karig, David K


    The fields of biosensing and bioremediation leverage the phenomenal array of sensing and metabolic capabilities offered by natural microbes. Synthetic biology provides tools for transforming these fields through complex integration of natural and novel biological components to achieve sophisticated sensing, regulation, and metabolic function. However, the majority of synthetic biology efforts are conducted in living cells, and concerns over releasing genetically modified organisms constitute a key barrier to environmental applications. Cell-free protein expression systems offer a path towards leveraging synthetic biology, while preventing the spread of engineered organisms in nature. Recent efforts in the areas of cell-free approaches for sensing, regulation, and metabolic pathway implementation, as well as for preserving and deploying cell-free expression components, embody key steps towards realizing the potential of cell-free systems for environmental sensing and remediation. Copyright © 2017 The Author. Published by Elsevier Ltd.. All rights reserved.

  12. Secretory products of breast cancer cells specifically affect human osteoblastic cells: partial characterization of active factors. (United States)

    Siwek, B; Lacroix, M; De Pollak, C; Marie, P; Body, J J


    The pathogenesis of tumor-induced osteolysis (TIO) following breast cancer metastases in bone remains unclear. We postulated that osteoblasts could be target cells for the secretory products of breast cancer cells. We previously showed that serum-free conditioned medium (CM) of the breast cancer cell line MCF-7 inhibits DNA synthesis by 75% of control values in osteoblast-like cells SaOS-2 and that this effect is only in a minor part due to transforming growth factor beta secretion. To establish the specificity of our observations and to look for other biologically active factors, we have tested the effects of medium conditioned by several cancer and noncancer cell lines (breast, colon, placenta, or fibrosarcoma) on the proliferation of osteoblast-like cells (SaOS-2, MG-63), normal human osteoblasts, human fibrosarcoma cells, and normal human fibroblasts. Culture medium (1:2) of the breast cancer cell lines MCF-7, T-47D, MDA-MB-231, and SK-BR-3 inhibited by 25-50% the proliferation of osteoblast-like cells SaOS-2, MG-63, and normal osteoblasts as evaluated by the MTT survival test or [3H]thymidine incorporation. MCF-7 cells completely inhibited the proliferation of normal human osteoblasts in coculture. This inhibitory effect was reversible and not due to cytotoxicity. Moreover, the cyclic adenosine monophosphate (cAMP) response to parathyroid hormone (PTH) of osteoblast-like cells SaOS-2 was also increased by 100-240% by the same CM. Such activities were, however, not detected in medium from the breast noncancer cell line HBL-100 or in the medium conditioned by non-breast cancer cell lines (COLO 320DM, HT-29, JAR, or HT-1080). Medium from the breast cancer cells had no effect on normal human fibroblasts or fibrosarcoma cells (HT-1080), suggesting the specificity of their action on human osteoblasts. After partial purification by ultrafiltration and size-exclusion chromatography, we found that medium of T-47D cells contained at least three nonprostanoid factors of

  13. A cancer cell-specific fluorescent probe for imaging Cu2 + in living cancer cells (United States)

    Wang, Chao; Dong, Baoli; Kong, Xiuqi; Song, Xuezhen; Zhang, Nan; Lin, Weiying


    Monitoring copper level in cancer cells is important for the further understanding of its roles in the cell proliferation, and also could afford novel copper-based strategy for the cancer therapy. Herein, we have developed a novel cancer cell-specific fluorescent probe for the detecting Cu2 + in living cancer cells. The probe employed biotin as the cancer cell-specific group. Before the treatment of Cu2 +, the probe showed nearly no fluorescence. However, the probe can display strong fluorescence at 581 nm in response to Cu2 +. The probe exhibited excellent sensitivity and high selectivity for Cu2 + over the other relative species. Under the guidance of biotin group, could be successfully used for detecting Cu2 + in living cancer cells. We expect that this design strategy could be further applied for detection of the other important biomolecules in living cancer cells.

  14. Are cancer cells really softer than normal cells? (United States)

    Alibert, Charlotte; Goud, Bruno; Manneville, Jean-Baptiste


    Solid tumours are often first diagnosed by palpation, suggesting that the tumour is more rigid than its surrounding environment. Paradoxically, individual cancer cells appear to be softer than their healthy counterparts. In this review, we first list the physiological reasons indicating that cancer cells may be more deformable than normal cells. Next, we describe the biophysical tools that have been developed in recent years to characterise and model cancer cell mechanics. By reviewing the experimental studies that compared the mechanics of individual normal and cancer cells, we argue that cancer cells can indeed be considered as softer than normal cells. We then focus on the intracellular elements that could be responsible for the softening of cancer cells. Finally, we ask whether the mechanical differences between normal and cancer cells can be used as diagnostic or prognostic markers of cancer progression. © 2017 Société Française des Microscopies and Société de Biologie Cellulaire de France. Published by John Wiley & Sons Ltd.

  15. Of germ cells, trophoblasts, and cancer stem cells. (United States)

    Burleigh, Angela R


    The trophoblastic theory of cancer, proposed in the early 1900s by Dr John Beard, may not initially seem relevant to current cancer models and treatments. However, the underpinnings of this theory are remarkably similar to those of the cancer stem cell (CSC) theory. Beard noticed that a significant fraction of germ cells never reach their final destination as they migrate during embryonic development from the hindgut to the germinal ridge. In certain situations, upon aberrant stimulation, these vagrant germ cells are able to generate tumors. Simplistically, the CSC theory surmises that a small population of tumorigenic cells exists, which initiate and maintain tumors, and these cells have a likely origin in normal stem cells. Both these theories are based on the potential of a single primitive cell to form a tumor. This has a major implication for cancer therapy, in that only a small percentage of cells need to be targeted to ablate a tumor.

  16. Stem cell biology and the plasticity polemic. (United States)

    Quesenberry, Peter J; Dooner, Gerri; Colvin, Gerald; Abedi, Mehrdad


    Characterization of a cord blood derived unrestricted somatic stem cell (USSC) with capacity to differentiate into hematopoietic and nonhematopoietic tissues in the absence of cell fusion has highlighted the great potential of stem cell plasticity. A great variety of stem cell types have been defined and even the most pure marrow stem cells are highly heterogeneous. Data suggest that stem cells may exist in a continuum with continually and reversibly changing phenotype. These cells also possess a capacity to produce lung, liver, skin, and skeletal muscle under conditions of tissue injury. Arguments raised against the significance of adult marrow to nonmarrow conversions including the importance of cell fusion appear fallacious. We are at the beginning of an exciting and burgeoning field of research with great clinical potential.

  17. Single Cell Characterization of Prostate Cancer Circulating Tumor Cells (United States)


    CTCs from patient blood, a single T24 bladder and LNCaP prostate cancer cells, a pool of 8 prostate CTCs, and one leukocyte isolated from the blood...amplify 66% of mRNA pool from a single cell. Clustering analysis does differentiate CTCs from LNCaP and T24 bladder cell lines (Figure 4). At present we...profiles could distinguish a CTC from prostate cancer cell line LNCaP and T24 bladder cancer cell line.  There was intra and inter patient heterogeneity

  18. Triiodothyronine regulates cell growth and survival in renal cell cancer. (United States)

    Czarnecka, Anna M; Matak, Damian; Szymanski, Lukasz; Czarnecka, Karolina H; Lewicki, Slawomir; Zdanowski, Robert; Brzezianska-Lasota, Ewa; Szczylik, Cezary


    Triiodothyronine plays an important role in the regulation of kidney cell growth, differentiation and metabolism. Patients with renal cell cancer who develop hypothyreosis during tyrosine kinase inhibitor (TKI) treatment have statistically longer survival. In this study, we developed cell based model of triiodothyronine (T3) analysis in RCC and we show the different effects of T3 on renal cell cancer (RCC) cell growth response and expression of the thyroid hormone receptor in human renal cell cancer cell lines from primary and metastatic tumors along with human kidney cancer stem cells. Wild-type thyroid hormone receptor is ubiquitously expressed in human renal cancer cell lines, but normalized against healthy renal proximal tube cell expression its level is upregulated in Caki-2, RCC6, SKRC-42, SKRC-45 cell lines. On the contrary the mRNA level in the 769-P, ACHN, HKCSC, and HEK293 cells is significantly decreased. The TRβ protein was abundant in the cytoplasm of the 786-O, Caki-2, RCC6, and SKRC-45 cells and in the nucleus of SKRC-42, ACHN, 769-P and cancer stem cells. T3 has promoting effect on the cell proliferation of HKCSC, Caki-2, ASE, ACHN, SK-RC-42, SMKT-R2, Caki-1, 786-0, and SK-RC-45 cells. Tyrosine kinase inhibitor, sunitinib, directly inhibits proliferation of RCC cells, while thyroid hormone receptor antagonist 1-850 (CAS 251310‑57-3) has less significant inhibitory impact. T3 stimulation does not abrogate inhibitory effect of sunitinib. Renal cancer tumor cells hypostimulated with T3 may be more responsive to tyrosine kinase inhibition. Moreover, some tumors may be considered as T3-independent and present aggressive phenotype with thyroid hormone receptor activated independently from the ligand. On the contrary proliferation induced by deregulated VHL and or c-Met pathways may transgress normal T3 mediated regulation of the cell cycle.

  19. Biology at a single cell level

    CSIR Research Space (South Africa)

    Mthunzi, P


    Full Text Available :// Induced pluripotent stem cells differentiated in culture Transfecting neuroblastomas Neuroblastoma ? Brain cells ? 80 ? 120 billion neurons in human... brain ? Non- renewing cell type ? Neurons difficult to transfect with established protocols ? Susceptible to degenerative disorders: - Parkinson?s disease - Multiple sclerosis - Alzheimer's disease http...

  20. Autophagy regulates the stemness of cervical cancer stem cells

    Directory of Open Access Journals (Sweden)

    Yang Y


    Full Text Available Yi Yang,1,2 Li Yu,1 Jin Li,1 Ya Hong Yuan,1 Xiao Li Wang,1 Shi Rong Yan,1 Dong Sheng Li,1 Yan Ding1 1Hubei Key Laboratory of Embryonic Stem Cell Research, 2Reproductive Center, Taihe Hospital, Hubei University of Medicine, Shiyan, People’s Republic of China Abstract: Cancer stem cells (CSCs are a rare population of multipotent cells with the capacity to self-renew. It has been reported that there are CSCs in cervical cancer cells. Pluripotency-associated (PA transcription factors such as Oct4, Sox2, Nanog and CD44 have been used to isolate CSCs subpopulations. In this study, we showed that autophagy plays an important role in the biological behavior of cervical cancer cells. The expression of the autophagy protein Beclin 1 and LC3B was higher in tumorspheres established from human cervical cancers cell lines (and CaSki than in the parental adherent cells. It was also observed that the basal and starvation-induced autophagy flux was higher in tumorspheres than in the bulk population. Autophagy could regulate the expression level of PA proteins in cervical CSCs. In addition, CRISPR/Cas 9-mediated Beclin 1 knockout enhanced the malignancy of HeLa cells, leading to accumulation of PA proteins and promoted tumorsphere formation. Our findings suggest that autophagy modulates homeostasis of PA proteins, and Beclin 1 is critical for CSC maintenance and tumor development in nude mice. This demonstrates that a prosurvival autophagic pathway is critical for CSC maintenance. Keywords: cervical cancer, autophagy, cancer stem cell, LC3, Oct4

  1. Response of breast cancer cells and cancer stem cells to metformin and hyperthermia alone or combined.

    Directory of Open Access Journals (Sweden)

    Hyemi Lee

    Full Text Available Metformin, the most widely prescribed drug for treatment of type 2 diabetes, has been shown to exert significant anticancer effects. Hyperthermia has been known to kill cancer cells and enhance the efficacy of various anti-cancer drugs and radiotherapy. We investigated the combined effects of metformin and hyperthermia against MCF-7 and MDA-MB-231 human breast cancer cell, and MIA PaCa-2 human pancreatic cancer cells. Incubation of breast cancer cells with 0.5-10 mM metformin for 48 h caused significant clonogenic cell death. Culturing breast cancer cells with 30 µM metformin, clinically relevant plasma concentration of metformin, significantly reduced the survival of cancer cells. Importantly, metformin was preferentially cytotoxic to CD44(high/CD24(low cells of MCF-7 cells and, CD44(high/CD24(high cells of MIA PaCa-2 cells, which are known to be cancer stem cells (CSCs of MCF-7 cells and MIA PaCa-2 cells, respectively. Heating at 42°C for 1 h was slightly toxic to both cancer cells and CSCs, and it markedly enhanced the efficacy of metformin to kill cancer cells and CSCs. Metformin has been reported to activate AMPK, thereby suppressing mTOR, which plays an important role for protein synthesis, cell cycle progression, and cell survival. For the first time, we show that hyperthermia activates AMPK and inactivates mTOR and its downstream effector S6K. Furthermore, hyperthermia potentiated the effect of metformin to activate AMPK and inactivate mTOR and S6K. Cell proliferation was markedly suppressed by metformin or combination of metformin and hyperthermia, which could be attributed to activation of AMPK leading to inactivation of mTOR. It is conclude that the effects of metformin against cancer cells including CSCs can be markedly enhanced by hyperthermia.

  2. Stem cells: Biology and clinical potential

    African Journals Online (AJOL)

    ajl yemi


    Dec 30, 2011 ... between apoptosis and self renewal. Yale J. Biol. Med. 82: 7-18. Alhadlaq A, Mao JJ (2004). Mesenchymal stem cells: isolation and therapeutics. Stem Cells Dev. 13: 436-448. Allan LE, Petit GH, Brundin P (2010). Cell transplantation in Parkinson's disease: problems and perspectives. Curr. Opin. Neurol.

  3. Lipid Storage and Autophagy in Melanoma Cancer Cells

    Directory of Open Access Journals (Sweden)

    Claudia Giampietri


    Full Text Available Cancer stem cells (CSC represent a key cellular subpopulation controlling biological features such as cancer progression in all cancer types. By using melanospheres established from human melanoma patients, we compared less differentiated melanosphere-derived CSC to differentiating melanosphere-derived cells. Increased lipid uptake was found in melanosphere-derived CSC vs. differentiating melanosphere-derived cells, paralleled by strong expression of lipogenic factors Sterol Regulatory Element-Binding Protein-1 (SREBP-1 and Peroxisome Proliferator-Activated Receptor-γ (PPAR-γ. An inverse relation between lipid-storing phenotype and autophagy was also found, since microtubule-associated protein 1A/1B-Light Chain 3 (LC3 lipidation is reduced in melanosphere-derived CSC. To investigate upstream autophagy regulators, Phospho-AMP activated Protein Kinase (P-AMPK and Phospho-mammalian Target of Rapamycin (P-mTOR were analyzed; lower P-AMPK and higher P-mTOR expression in melanosphere-derived CSC were found, thus explaining, at least in part, their lower autophagic activity. In addition, co-localization of LC3-stained autophagosome spots and perilipin-stained lipid droplets was demonstrated mainly in differentiating melanosphere-derived cells, further supporting the role of autophagy in lipid droplets clearance. The present manuscript demonstrates an inverse relationship between lipid-storing phenotype and melanoma stem cells differentiation, providing novel indications involving autophagy in melanoma stem cells biology.

  4. Applied Developmental Biology: Making Human Pancreatic Beta Cells for Diabetics. (United States)

    Melton, Douglas A


    Understanding the genes and signaling pathways that determine the differentiation and fate of a cell is a central goal of developmental biology. Using that information to gain mastery over the fates of cells presents new approaches to cell transplantation and drug discovery for human diseases including diabetes. © 2016 Elsevier Inc. All rights reserved.

  5. Establishment of Cancer Stem Cell Cultures from Human Conventional Osteosarcoma. (United States)

    Palmini, Gaia; Zonefrati, Roberto; Mavilia, Carmelo; Aldinucci, Alessandra; Luzi, Ettore; Marini, Francesca; Franchi, Alessandro; Capanna, Rodolfo; Tanini, Annalisa; Brandi, Maria Luisa


    The current improvements in therapy against osteosarcoma (OS) have prolonged the lives of cancer patients, but the survival rate of five years remains poor when metastasis has occurred. The Cancer Stem Cell (CSC) theory holds that there is a subset of tumor cells within the tumor that have stem-like characteristics, including the capacity to maintain the tumor and to resist multidrug chemotherapy. Therefore, a better understanding of OS biology and pathogenesis is needed in order to advance the development of targeted therapies to eradicate this particular subset and to reduce morbidity and mortality among patients. Isolating CSCs, establishing cell cultures of CSCs, and studying their biology are important steps to improving our understanding of OS biology and pathogenesis. The establishment of human-derived OS-CSCs from biopsies of OS has been made possible using several methods, including the capacity to create 3-dimensional stem cell cultures under nonadherent conditions. Under these conditions, CSCs are able to create spherical floating colonies formed by daughter stem cells; these colonies are termed "cellular spheres". Here, we describe a method to establish CSC cultures from primary cell cultures of conventional OS obtained from OS biopsies. We clearly describe the several passages required to isolate and characterize CSCs.

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

    Directory of Open Access Journals (Sweden)

    Thomas W.J. Lennard


    Full Text Available 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