The Experts below are selected from a list of 4770 Experts worldwide ranked by ideXlab platform
Jhingook Kim - One of the best experts on this subject based on the ideXlab platform.
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a Multicellular Spheroid formation and extraction chip using removable cell trapping barriers
Transactions of The Korean Society of Mechanical Engineers A, 2011Co-Authors: Hyejin Jin, Youngho Cho, Taeyoon Kim, Jhingook KimAbstract:We propose a Spheroid chip that uses removable cell trapping barriers and that is capable of forming and extracting Multicellular Spheroids. By using a conventional well plate and flask, it is difficult to form small-sized Spheroids, which resemble avascular 3D cell-cell interaction. It was difficult to extract Spheroids using conventional microchips and fixed cell trapping barriers. The proposed chip, however, facilitates both formation and extraction of Spheroids by using removable cell trapping barriers formed by membrane deflection. The cell trapping barriers, formed at the membrane pressure of 50 kPa, hold the cells in the trapping region at a cell inlet pressure of 145.155 Pa. After incubation for 24 h, the trapped cells form uniform Spheroids. We successfully extract the Spheroids at a cell inlet pressure of 5 kPa after removing the membrane pressure. The extracted Spheroids have a diameter of with a viability of . Using the proposed chip, uniform Spheroids can be formed and these Spheroids can be safely extracted for carrying out the post-processing of Spheroids.
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a Multicellular Spheroid formation and extraction chip using removable cell trapping barriers
Lab on a Chip, 2011Co-Authors: Hyejin Jin, Youngho Cho, Jhingook KimAbstract:This paper presents a Multicellular Spheroid chip capable of forming and extracting three-dimensional (3D) Spheroids using removable cell trapping barriers. Compared to the conventional macro-scale Spheroid formation methods, including spinning, hanging-drop, and liquid-overlay methods, the recent micro-scale Spheroid chips have the advantage of forming smaller Spheroids with better uniformity. The recent micro Spheroid chips, however, have difficulties in extracting the Spheroids due to fixed cell trapping barriers. The present Spheroid chip, having two PDMS layers, uses removable cell trapping barriers, thereby making it easy to form and extract uniform and small-sized Spheroids. We have designed, fabricated and characterized a 4 × 1 Spheroid chip, where membrane cell trapping barriers are inflated at a pressure of 50 kPa for Spheroid formation and are deflated at zero gauge pressure for simple and safe extraction of the Spheroids formed. In this experimental study, the cell suspension of non-small lung cancer cells, H1650, is supplied to the fabricated Spheroid chip in the pressure range 145–155 Pa. The fabricated Spheroid chips collect the cancer cells in the cell trapping regions from the cell suspension at a concentration of 2 × 106 ml−1, thus forming uniform 3D Spheroids with a diameter of 197.2 ± 11.7 μm, after 24 h incubation at 5% CO2 and 37°C environment. After the removal of the cell trapping barriers, the Spheroids formed were extracted through the outlet ports at a cell inlet pressure of 5 kPa. The cells in the extracted Spheroids showed a viability of 80.3 ± 7.7%. The present Spheroid chip offers a simple and effective method of obtaining uniform and small-sized 3D Spheroids for the next stage of cell-based biomedical research, such as gene expression analysis and Spheroid inoculation in animal models.
H. Acker - One of the best experts on this subject based on the ideXlab platform.
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the use of human tumor cells grown in Multicellular Spheroid culture for designing and improving therapeutic strategies
Journal of Theoretical Medicine, 1998Co-Authors: H. AckerAbstract:Human turnor cells grown in threedimensional Multicellular spheriod culture represent an ideal system to study the heterogeneous interaction between microenvironment and different therpeutic modalities in patients. Overcoming this hetergenenity is the most challeging task for the improvement of cancer theraphy. Examples of this interaction are given with the meaning of pO2 and pH for the treatment of tumor cells with radition cytostatic,cytokines and gene therapy. The presented result might form a base for the use of muticellular spheriods in a concerted action between clinicians, biologist and mathematicians to improve tumor therapy individually for patient.
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effects of cobalt on haem proteins of erythropoietin producing hepg2 cells in Multicellular Spheroid culture
FEBS Letters, 1994Co-Authors: A Gorlach, Joachim Fandrey, Georg Holtermann, H. AckerAbstract:The hypoxia-induced increase of spectrophotometrically measured light absorption at 560 nm, considered as reduced cytochrome b, in HepG2 cells is diminished after exposure to cobalt chloride (50 or 100 μM) for 18–36h. The redox state of cytochrome c and cytochrome aa3, however, remains stable, indicating a particular affinity of cytochrome b for cobalt. Erythropoietin production of HepG2 cells increases after application of cobalt chloride, whereas H2O2 production, as measured by the dihydrorhodamine technique, decreases. It is concluded that cobalt stimulates a signal cascade with cytochrome b as receptor and H2O2 as second messenger for regulating erythropoietin production.
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the relationship of radiation sensitivity and microenvironment of human tumor cells in Multicellular Spheroid tissue culture
Advances in Experimental Medicine and Biology, 1994Co-Authors: A Gorlach, H. AckerAbstract:Despite many publications describing a correlation between radioresistance and radiobiological hypoxia (Adams, 1990; Hill and Pallavicini,1984; Rockwell and Moulder, 1990) the importance of this phenomenon is still under discussion as well as the mechanisms relevant for the outcome to radiotherapy (Deacon et al.,1984; Steel and Peacock,1989).
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influence of glucose on metabolism and growth of rat glioma cells c6 in Multicellular Spheroid culture
International Journal of Cancer, 1992Co-Authors: H. Acker, G Holtermann, B Bolling, Jörgen CarlssonAbstract:cells in multicel- lular Spheroid culture depended strongly on the glucose supply. A low glucose level (0.1 g/l) in the culture medium reduced lactate production, increased oxygen consumption and dimin- ished hydrogen ion production under normoxia as well as hypoxia. A high glucose level (10 g/l glucose) increased lactate production, had no significant influence on oxygen consumption and increased the hydrogen ion production under hypoxia. Hydrogen ion release from cells under normoxic and hypoxic conditions could be significantly diminished by amiloride (I mM), indicating the involvement of the Na+/H+ exchanger. The growth of the C6 Spheroids was enhanced under low glucose conditions, possibly due to the more physiological extracellular pH in the deeper regions of the Spheroids. The growth was inhibited under high glucose conditions, which seemed to be toxic due to a massive hydrogen production giving acidosis. The glucose supply strongly influenced the local hydrogen ion produc- tion inside the
Simon D. Angus - One of the best experts on this subject based on the ideXlab platform.
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a quantitative cellular automaton model of in vitro Multicellular Spheroid tumour growth
Journal of Theoretical Biology, 2009Co-Authors: Monika Joanna Piotrowska, Simon D. AngusAbstract:Abstract We report numerical results from a 2D cellular automaton (CA) model describing the dynamics of the in vitro cultivated Multicellular Spheroid obtained from EMT6/Ro (mammary carcinoma) cell line. Significantly, the CA model relaxes the often assumed one-to-one correspondence between cells and CA sites so as to correctly model the peripheral mitotic boundary region, and to enable the study of necrosis in large avascular tumours. By full calibration and scaling to available experimental data, the model produces with good accuracy experimentally comparable data on a range of bulk tumour kinetics and necrosis measures. Our main finding is that the metabolic production of H + ions is not sufficient to cause central necrosis prior to the sub-viable nutrient-deficient stage of tumour development being reached. Thus, the model suggests that an additional process is required to explain the experimentally observable onset of necrosis prior to the non-viable nutrient-deficient point being reached.
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A quantitative cellular automaton model of Multicellular Spheroid tumour growth
Journal of Theoretical Biology, 2009Co-Authors: Monika Joanna Piotrowska, Simon D. AngusAbstract:We report numerical results from a two dimensional Cellular Automaton (CA) model describing the dynamics of the cultivated Multicellular Spheroid obtained from EMT6/Ro (mammary carcinoma) cell line. Significantly, the CA model relaxes the often assumed one-to-one correspondence between cells and CA sites so as to correctly model the peripheral mitotic boundary region, and to enable the study of necrosis in large avascular tumours. By full calibration and scaling to available experimental data, the model produces with good accuracy experimentally comparable data on a range of bulk tumour kinetics and necrosis measures. Our main finding is that the metabolic production of H ions is not sufficient to cause central necrosis prior to the sub-viable nutrient-deficient stage of tumour development being reached. Thus, the model suggests that an additional process is required to explain the experimentally observable onset of necrosis prior to the non-viable nutrient-deficient point being reached.
Alice S T Wong - One of the best experts on this subject based on the ideXlab platform.
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modeling ovarian cancer Multicellular Spheroid behavior in a dynamic 3d peritoneal microdevice
Journal of Visualized Experiments, 2017Co-Authors: Matthew Y H Tang, Susan Yung, Tak Mao Chan, Mengsu Yang, Ho Cheung Shum, Alice S T WongAbstract:Ovarian cancer is characterized by extensive peritoneal metastasis, with tumor spheres commonly found in the malignant ascites. This is associated with poor clinical outcomes and currently lacks effective treatment. Both the three-dimensional (3D) environment and the dynamic mechanical forces are very important factors in this metastatic cascade. However, traditional cell cultures fail to recapitulate this natural tumor microenvironment. Thus, in vivo-like models that can emulate the intraperitoneal environment are of obvious importance. In this study, a new microfluidic platform of the peritoneum was set up to mimic the situation of ovarian cancer Spheroids in the peritoneal cavity during metastasis. Ovarian cancer Spheroids generated under a non-adherent condition were cultured in microfluidic channels coated with peritoneal mesothelial cells subjected to physiologically relevant shear stress. In summary, this dynamic 3D ovarian cancer-mesothelium microfluidic platform can provide new knowledge on basic cancer biology and serve as a platform for potential drug screening and development.
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a novel p70 s6 kinase microrna biogenesis axis mediates Multicellular Spheroid formation in ovarian cancer progression
Oncotarget, 2016Co-Authors: Sophia So Ngo Lam, Abby S C Mak, Alice S T WongAbstract:// Sophia So Ngo Lam 1 , Carman Ka Man Ip 1 , Abby Sin Chi Mak 1 , Alice Sze Tsai Wong 1 1 School of Biological Sciences, University of Hong Kong, Hong Kong Correspondence to: Alice Sze Tsai Wong, e-mail: awong1@hku.hk Keywords: p70 S6 kinase, microRNA biogenesis, Multicellular Spheroid formation, ovarian cancer Received: January 06, 2016 Accepted: April 26, 2016 Published: May 13, 2016 ABSTRACT Ovarian cancer is the leading cause of death of all gynecologic tumors, associated with widespread peritoneal dissemination and malignant ascites. Key to this is the ability to form Multicellular Spheroids (MCS); however, the tumor-specific factors that regulate MCS formation are unclear. p70 S6 kinase (p70 S6K ), which is a downstream effector of phosphatidylinositol 3-kinase/Akt, is frequently constitutively active in ovarian carcinoma. Here we identify p70 S6K as a vital regulator of MCS formation. We also uncover a new mechanism of p70 S6K function as a component of the microRNA biogenesis machinery in this process. We show that p70 S6K phosphorylates, and inhibits the interaction of tristetraprolin (TTP) and Dicer that promotes the expression of a subset of miRNAs, including the maturation of miR-145. Twist and Sox9 are two divergent targets of miR-145, thereby enhancing N-cadherin, but not other cadherin, expression and MCS formation. Activating miR-145 suppresses ovarian tumor growth and metastasis in an orthotopic xenograft mouse model. Meta-analysis in the Oncomine database reveals that high p70 S6K and low TTP levels are associated with ovarian tumor progression. These results define a critical link between p70 S6K , miRNA maturation, and MCS formation that may underlie poor clinical outcome of ovarian cancer patients for developing novel therapeutic strategies.
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p70 s6 kinase drives ovarian cancer metastasis through Multicellular Spheroid peritoneum interaction and p cadherin b1 integrin signaling activation
Oncotarget, 2014Co-Authors: Susan Yung, Tak Mao Chan, Saiwah Tsao, Alice S T WongAbstract:Peritoneal dissemination as a manifestation of ovarian cancer is an adverse prognostic factor associated with poor clinical outcome, and is thus a potentially promising target for improved treatment. Sphere forming cells (Multicellular Spheroids) present in malignant ascites of patients with ovarian cancer represent a major impediment to effective treatment. p70 S6 kinase (p70S6K), which is a downstream effector of mammalian target of rapamycin, is frequently hyperactivated in human ovarian cancer. Here, we identified p70S6K as an important regulator for the seeding and successful colonization of ovarian cancer Spheroids on the peritoneum. Furthermore, we provided evidence for the existence of a novel crosstalk between P-cadherin and β1 integrin, which was crucial for the high degree of specificity in cell adhesion. In particular, we demonstrated that the upregulation of mature β1 integrin occurred as a consequence of P-cadherin expression through the induction of the Golgi glycosyltransferase, ST6Gal-I, which mediated β1 integrin hypersialylation. Loss of p70S6K or targeting the P-cadherin/β1-integrin interplay could significantly attenuate the metastatic spread onto the peritoneum in vivo. These findings establish a new role for p70S6K in tumor Spheroid-mesothelium communication in ovarian cancer and provide a preclinical rationale for targeting p70S6K as a new avenue for microenvironment-based therapeutic strategy.
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p70 s6 kinase drives ovarian cancer metastasis through Multicellular Spheroid peritoneum interaction and p cadherin b1 integrin signaling activation
Oncotarget, 2014Co-Authors: Carman K M Ip, Tak Mao Chan, Susan Yung, Saiwah Tsao, Alice S T WongAbstract:// Carman Ka Man Ip 1 , Susan Yung 2 , Tak-Mao Chan 2 , Sai-Wah Tsao 3 , Alice Sze Tsai Wong 1 1 School of Biological Sciences, University of Hong Kong, Pokfulam Road, Hong Kong 2 Department of Medicine, University of Hong Kong, Sassoon Road, Hong Kong 3 Department of Anatomy, University of Hong Kong, Sassoon Road, Hong Kong Correspondence to: Dr. Alice Sze Tsai Wong, email: awong1@hku.hk Keywords: p70 S6K , P-cadherin, β1 integrin, adhesion, metastasis Received: May 21, 2014 Accepted: August 18, 2014 Published: August 21, 2014 ABSTRACT Peritoneal dissemination as a manifestation of ovarian cancer is an adverse prognostic factor associated with poor clinical outcome, and is thus a potentially promising target for improved treatment. Sphere forming cells (Multicellular Spheroids) present in malignant ascites of patients with ovarian cancer represent a major impediment to effective treatment. p70 S6 kinase (p70 S6K ), which is a downstream effector of mammalian target of rapamycin, is frequently hyperactivated in human ovarian cancer. Here, we identified p70 S6K as an important regulator for the seeding and successful colonization of ovarian cancer Spheroids on the peritoneum. Furthermore, we provided evidence for the existence of a novel crosstalk between P-cadherin and β1 integrin, which was crucial for the high degree of specificity in cell adhesion. In particular, we demonstrated that the upregulation of mature β1 integrin occurred as a consequence of P-cadherin expression through the induction of the Golgi glycosyltransferase, ST6Gal-I, which mediated β1 integrin hypersialylation. Loss of p70 S6K or targeting the P-cadherin/β1-integrin interplay could significantly attenuate the metastatic spread onto the peritoneum in vivo . These findings establish a new role for p70 S6K in tumor Spheroid-mesothelium communication in ovarian cancer and provide a preclinical rationale for targeting p70 S6K as a new avenue for microenvironment-based therapeutic strategy.
N K Uzunoglu - One of the best experts on this subject based on the ideXlab platform.
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simulating growth dynamics and radiation response of avascular tumour Spheroids model validation in the case of an emt6 ro Multicellular Spheroid
Computer Methods and Programs in Biomedicine, 2004Co-Authors: Evangelia I Zacharaki, Georgios S Stamatakos, Konstantina S Nikita, N K UzunogluAbstract:The goal of this paper is to provide both the basic scientist and the clinician with an advanced computational tool for performing in silico experiments aiming at supporting the process of biological optimisation of radiation therapy. Improved understanding and description of malignant tumour dynamics is an additional intermediate objective. To this end an advanced three-dimensional (3D) Monte-Carlo simulation model of both the avascular development of Multicellular tumour Spheroids and their response to radiation therapy is presented. The model is based upon a number of fundamental biological principles such as the transition between the cell cycle phases, the diffusion of oxygen and nutrients and the cell survival probabilities following irradiation. Efficient algorithms describing tumour expansion and shrinkage are proposed and applied. The output of the biosimulation model is introduced into the (3D) visualisation package AVS-Express, which performs the visualisation of both the external surface and the internal structure of the dynamically evolving tumour based on volume or surface rendering techniques. Both the numerical stability and the statistical behaviour of the simulation model have been studied and evaluated for the case of EMT6/Ro Spheroids. Predicted histological structure and tumour growth rates have been shown to be in agreement with published experimental data. Furthermore, the underlying structure of the tumour Spheroid as well as its response to irradiation satisfactorily agrees with laboratory experience.