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Sample records for cancer establishes model

  1. Establishment and bronchial arteriography of the models of canine lung cancer

    Cao Xicai; Wang Xiaodong; Li Bin; Shi Jianguang; Liu Yong; Xu Nanxun; Ma Weijun; Yang Haixian; Bai Jingwen; Li Weidong; Liu Shuping; Liu Anpu

    2003-01-01

    Objective: To investigate the establishment and bronchial arteriography of the models of canine lung cancer, and to facilitate further diagnosis and treatment of lung cancer. Methods: Twenty-two dogs were respectively administrated with 3 ml suspension of lipiodol-ultrafluid mixed with 3- methylcholanthrene (MCA) and diethylnitrosamine (DEN). The suspension was injected into the diaphragmic lobe of right lung with the co-axial catheter through endotracheal intubation. The dogs were randomly divided into 5 groups, group A (4 dogs), B (4), C (4), D (5), and E (5), which were sacrificed after observation for 1, 3, 6, 12, and 18 months, respectively. Then the image analysis and histopathologic examinations were carried out at different period. 5 dogs in group E were examined by bronchial arteriography. Results: Peribronchiolitis and atelectasis appeared at early stage (one month). Chronic granulomatous inflammation and fibrosis of lung tissue were gradually formed after 3 months. Proliferation of stem cells in bronchioles and atypical hyperplasia were found from 6 to 12 months. At last, the squamous carcinoma and bronchioloalveolar carcinoma were induced after 18 months. The lung cancer and precancerous lesion were found in 4 of 5 dogs at the 18 th month. The bronchial arteriography in the 5 dogs showed that 3 bronchial arteries were found as the supplying blood artery to the tumor. Conclusion: The suspension of lipiodol-ultrafluid mixed with MCA and DEN was exactly injected with the co-axial catheter through endotracheal intubation to establish the models of canine lung cancer. The inducible rate of the method was high and the location of lung cancer was accurate. It was affirmed that the blood supply artery of canine lung cancer was bronchial artery. Bronchial arteriography was of momentous significance to the diagnosis of early lung cancer. The establishment of the models of canine lung cancer was significant in the diagnosis and treatment of lung cancer. The models

  2. Establishment and identification of a rabbit model of peritoneal carcinomatosis from gastric cancer

    Mei, Lie-Jun; Yang, Xiao-Jun; Tang, Li; Hassan, Alaa Hammed al-shammaa; Yonemura, Yutaka; Li, Yan

    2010-01-01

    Gastric cancer peritoneal carcinomatosis is a common clinical problem, but there are no suitable large animal models to study this problem. This study was to establish a stable rabbit peritoneal carcinomatosis model of gastric cancer using VX2 tumor, and analyze the clinico-pathological features. VX2 tumor was implanted into 36 New Zealand rabbits by 3 methods: laparotomic orthotopic injection of cancer cells into the submucosal layer of the stomach (Group A), laparotomic implantation of tumor tissue into the greater omentum immediately beneath the gastric antrum (Group B), and percutaneous injection of tumor cells directly into the peritoneal cavity (Group C), 12 rabbits in each group. The animals were closely observed and detailed clinico-pathological studies were conducted. The success rates of peritoneal carcinomatosis formation were 100% (12/12), 91.7% (11/12) and 58.3% (7/12), respectively, for Groups A, B and C (P = 0.019, A versus C; P = 0.077, B versus C; P = 0.500, A versus B, Fisher's exact test). Two weeks after submucosal cancer cells injection in Group A, ulcerative gastric cancer with peritoneal carcinomatosis showed typical VX2 tumor pathology, with widespread intraperitoneal metastatic nodules, bloody ascites and perspicuous pulmonary metastases. The clinico-pathological progression pattern was very similar to patients of advanced gastric cancer with peritoneal carcinomatosis. Groups B and C showed similar pattern of cancer progression, but less aggressive. First large animal model of peritoneal carcinomatosis from gastric cancer has been established by laparotomic orthotopic injection of VX2 cancer cells into the submucosal layer of the stomach, providing a more suitable model for surgical interventional studies. The clinico-pathological features of this model resemble human peritoneal carcinomatosis

  3. Establishment of an orthotopic lung cancer model in nude mice and its evaluation by spiral CT.

    Liu, Xiang; Liu, Jun; Guan, Yubao; Li, Huiling; Huang, Liyan; Tang, Hailing; He, Jianxing

    2012-04-01

    To establish a simple and highly efficient orthotopic animal model of lung cancer cell line A549 and evaluate the growth pattern of intrathoracic tumors by spiral CT. A549 cells (5×10(6) mL(-1)) were suspended and inoculated into the right lung of BALB/c nude mice via intrathoracic injection. Nude mice were scanned three times each week by spiral CT after inoculation of lung cancer cell line A549. The survival time and body weight of nude mice as well as tumor invasion and metastasis were examined. Tissue was collected for subsequent histological assay after autopsia of mice. The tumor-forming rate of the orthotopic lung cancer model was 90%. The median survival time was 30.7 (range, 20-41) days. The incidence of tumor metastasis was 100%. The mean tumor diameter and the average CT value gradually increased in a time-dependent manner. The method of establishing the orthotopic lung cancer model through transplanting A549 cells into the lung of nude mice is simple and highly successful. Spiral CT can be used to evaluate intrathoracic tumor growth in nude mice vividly and dynamically.

  4. Establishment of Orthotopic Xuanwei Lung Cancer SCID Mouse Model 
and Analysis of Biological Properties

    Yongchun ZHOU

    2012-08-01

    Full Text Available Background and objective The incidence of Xuanwei lung cancer ranks first in China, and its pathogenesis requires in-depth investigation. This study aims to establish an orthotopic Xuanwei lung cancer severe combined immunodeficiency (SCID mouse model and to provide a basic experimental platform for further study. Methods The Xuanwei lung cancer cell line XWLC-05 was inoculated into the lung tissue of SCID mice in high and low doses. The tumor formation rates, tumor characteristics, spontaneous metastases, and survival times of the mice were observed, taking a subcutaneously transplanted tumor as control. Results The tumor formation rates of the orthotopic transplantation of lung cancer cells in high and low doses were 81% and 83%, respectively, among which mice in the high-dose group appeared cachectic on day 13. Extensive invasion and adhesion were observed in the contralateral lung and thoracic cavity, but no distant metastasis was exhibited. Mice with low-dose cells in the orthotopic transplantation group appeared cachectic and distant metastasis occurred on day 25. The tumor formation rates in the subcutaneous inoculation group by the high and low doses of cells were 100% and 94.5%, respectively, and no distant metastasis was observed. The rate of metastasis within the orthotopic transplantation group and between the orthotopic and subcutaneous inoculation groups showed a significant difference (P<0.05. A significant difference was indicated by the survival rate within and between the groups (P<0.001. Conclusion We successfully established an orthotopic XWLC SCID mouse model, which lays the foundation for a more in-depth study.

  5. Establishment of animal model for the analysis of cancer cell metastasis during radiotherapy

    Park, Jong Kuk; Jang, Su Jin; Kang, Sung Wook; Park, Sunhoo; Hwang, Sang-Gu; Kim, Wun-Jae; Kang, Joo Hyun; Um, Hong-Duck

    2012-01-01

    Γ-Ionizing radiation (IR) therapy is one of major therapeutic tools in cancer treatment. Nevertheless, γ-IR therapy failed due to occurrence of metastasis, which constitutes a significant obstacle in cancer treatment. The main aim of this investigation was to construct animal model which present metastasis during radiotherapy in a mouse system in vivo and establishes the molecular mechanisms involved. The C6L transfectant cell line expressing firefly luciferase (fLuc) was treated with γ-IR, followed by immunoblotting, zymography and invasion assay in vitro. We additionally employed the C6L transfectant cell line to construct xenografts in nude mice, which were irradiated with γ-IR. Irradiated xenograft-containing mice were analyzed via survival curves, measurement of tumor size, and bioluminescence imaging in vivo and ex vivo. Metastatic lesions in organs of mice were further assessed using RT-PCR, H & E staining and immunohistochemistry. γ-IR treatment of C6L cells induced epithelial-mesenchymal transition (EMT) and increased cell invasion. In irradiated xenograft-containing mice, tumor sizes were decreased dramatically and survival rates extended. Almost all non-irradiated xenograft-containing control mice had died within 4 weeks. However, we also observed luminescence signals in about 22.5% of γ-IR-treated mice. Intestines or lungs of mice displaying luminescence signals contained several lesions, which expressed the fLuc gene and presented histological features of cancer tissues as well as expression of EMT markers. These findings collectively indicate that occurrences of metastases during γ-IR treatment accompanied induction of EMT markers, including increased MMP activity. Establishment of a murine metastasis model during γ-IR treatment should aid in drug development against cancer metastasis and increase our understanding of the mechanisms underlying the metastatic process

  6. Establishment of a biophysical model to optimize endoscopic targeting of magnetic nanoparticles for cancer treatment

    Roeth AA

    2017-08-01

    Full Text Available Anjali A Roeth,1,* Ioana Slabu,2,* Martin Baumann,2 Patrick H Alizai,1 Maximilian Schmeding,1 Gernot Guentherodt,3 Thomas Schmitz-Rode,2 Ulf P Neumann1 1Department of General, Visceral and Transplant Surgery, University Hospital RWTH Aachen, 2Institute of Applied Medical Engineering, Helmholtz-Institute Aachen, RWTH Aachen, Aachen, 3Institute of Physics A, RWTH Aachen University, Aachen, Germany *These authors contributed equally to this work Abstract: Superparamagnetic iron oxide nanoparticles (SPION may be used for local tumor treatment by coupling them to a drug and accumulating them locally with magnetic field traps, that is, a combination of permanent magnets and coils. Thereafter, an alternating magnetic field generates heat which may be used to release the thermosensitively bound drug and for hyperthermia. Until today, only superficial tumors can be treated with this method. Our aim was to transfer this method into an endoscopic setting to also reach the majority of tumors located inside the body. To find the ideal endoscopic magnetic field trap, which accumulates the most SPION, we first developed a biophysical model considering anatomical as well as physical conditions. Entities of choice were esophageal and prostate cancer. The magnetic susceptibilities of different porcine and rat tissues were measured with a superconducting quantum interference device. All tissues showed diamagnetic behavior. The evaluation of clinical data (computed tomography scan, endosonography, surgical reports, pathological evaluation of patients gave insight into the topographical relationship between the tumor and its surroundings. Both were used to establish the biophysical model of the tumors and their surroundings, closely mirroring the clinical situation, in which we could virtually design, place and evaluate different electromagnetic coil configurations to find optimized magnetic field traps for each tumor entity. By simulation, we could show that the

  7. Establishing the pig as a large animal model for vaccine development against human cancer

    Overgaard, Nana Haahr; Frøsig, Thomas Mørch; Welner, Simon

    2015-01-01

    Immunotherapy has increased overall survival of metastatic cancer patients, and cancer antigens are promising vaccine targets. To fulfill the promise, appropriate tailoring of the vaccine formulations to mount in vivo cytotoxic T cell (CTL) responses toward co-delivered cancer antigens is essential...... and the porcine immunome is closer related to the human counterpart, we here introduce pigs as a supplementary large animal model for human cancer vaccine development. IDO and RhoC, both important in human cancer development and progression, were used as vaccine targets and 12 pigs were immunized with overlapping......C-derived peptides across all groups with no adjuvant being superior. These findings support the further use of pigs as a large animal model for vaccine development against human cancer....

  8. Establishment of a biophysical model to optimize endoscopic targeting of magnetic nanoparticles for cancer treatment.

    Roeth, Anjali A; Slabu, Ioana; Baumann, Martin; Alizai, Patrick H; Schmeding, Maximilian; Guentherodt, Gernot; Schmitz-Rode, Thomas; Neumann, Ulf P

    2017-01-01

    Superparamagnetic iron oxide nanoparticles (SPION) may be used for local tumor treatment by coupling them to a drug and accumulating them locally with magnetic field traps, that is, a combination of permanent magnets and coils. Thereafter, an alternating magnetic field generates heat which may be used to release the thermosensitively bound drug and for hyperthermia. Until today, only superficial tumors can be treated with this method. Our aim was to transfer this method into an endoscopic setting to also reach the majority of tumors located inside the body. To find the ideal endoscopic magnetic field trap, which accumulates the most SPION, we first developed a biophysical model considering anatomical as well as physical conditions. Entities of choice were esophageal and prostate cancer. The magnetic susceptibilities of different porcine and rat tissues were measured with a superconducting quantum interference device. All tissues showed diamagnetic behavior. The evaluation of clinical data (computed tomography scan, endosonography, surgical reports, pathological evaluation) of patients gave insight into the topographical relationship between the tumor and its surroundings. Both were used to establish the biophysical model of the tumors and their surroundings, closely mirroring the clinical situation, in which we could virtually design, place and evaluate different electromagnetic coil configurations to find optimized magnetic field traps for each tumor entity. By simulation, we could show that the efficiency of the magnetic field traps can be enhanced by 38-fold for prostate and 8-fold for esophageal cancer. Therefore, our approach of endoscopic targeting is an improvement of the magnetic drug-targeting setups for SPION tumor therapy as it holds the possibility of reaching tumors inside the body in a minimal-invasive way. Future animal experiments must prove these findings in vivo.

  9. [Establishment of risk evaluation model of peritoneal metastasis in gastric cancer and its predictive value].

    Zhao, Junjie; Zhou, Rongjian; Zhang, Qi; Shu, Ping; Li, Haojie; Wang, Xuefei; Shen, Zhenbin; Liu, Fenglin; Chen, Weidong; Qin, Jing; Sun, Yihong

    2017-01-25

    To establish an evaluation model of peritoneal metastasis in gastric cancer, and to assess its clinical significance. Clinical and pathologic data of the consecutive cases of gastric cancer admitted between April 2015 and December 2015 in Department of General Surgery, Zhongshan Hospital of Fudan University were analyzed retrospectively. A total of 710 patients were enrolled in the study after 18 patients with other distant metastasis were excluded. The correlations between peritoneal metastasis and different factors were studied through univariate (Pearson's test or Fisher's exact test) and multivariate analyses (Binary Logistic regression). Independent predictable factors for peritoneal metastasis were combined to establish a risk evaluation model (nomogram). The nomogram was created with R software using the 'rms' package. In the nomogram, each factor had different scores, and every patient could have a total score by adding all the scores of each factor. A higher total score represented higher risk of peritoneal metastasis. Receiver operating characteristic (ROC) curve analysis was used to compare the sensitivity and specificity of the established nomogram. Delong. Delong. Clarke-Pearson test was used to compare the difference of the area under the curve (AUC). The cut-off value was determined by the AUC, when the ROC curve had the biggest AUC, the model had the best sensitivity and specificity. Among 710 patients, 47 patients had peritoneal metastasis (6.6%), including 30 male (30/506, 5.9%) and 17 female (17/204, 8.3%); 31 were ≥ 60 years old (31/429, 7.2%); 38 had tumor ≥ 3 cm(38/461, 8.2%). Lauren classification indicated that 2 patients were intestinal type(2/245, 0.8%), 8 patients were mixed type(8/208, 3.8%), 11 patients were diffuse type(11/142, 7.7%), and others had no associated data. CA19-9 of 13 patients was ≥ 37 kU/L(13/61, 21.3%); CA125 of 11 patients was ≥ 35 kU/L(11/36, 30.6%); CA72-4 of 11 patients was ≥ 10 kU/L(11/39, 28

  10. Antimetabolites: Established cancer therapy

    Manjul Tiwari

    2012-01-01

    Full Text Available Cell death has been divided into two main types: programmed cell death, in which the cell plays an active role, and passive (necrotic cell death. Senescence arrest, accelerated senescence and differentiation are also responses that can be induced in response to DNA-damaging agents. Apoptosis may occur as a primary event following chemotherapy, in which genes that regulate apoptosis will influence the outcome of therapy or, alternatively, as an event secondary to the induction of lethal damage that involves the subsequent processing of cellular damage. The particular type of response induced is highly dependent on the agent and dose employed, the type of DNA damage induced as well as the genetic and cellular phenotypes. It has been proposed that apoptosis may play a lesser role in tumor response to radiation in comparison with the induction of cell death through mitotic catastrophe or a senescence-like irreversible growth arrest. However, in comparison with the induction of apoptosis, there is a lack of as much definitive information on other cell death processes that occur in cancer cells in response to chemotherapeutic agents, including antimetabolites. This article reviews what is known about these processes at the present time in response to experimental or clinically used agents that are analogs of 5-fluorouracil, cytidine or purines, hydroxyurea, or that belong to the family of folate antagonists.

  11. Establishing magnetic resonance imaging as an accurate and reliable tool to diagnose and monitor esophageal cancer in a rat model.

    Juliann E Kosovec

    Full Text Available OBJECTIVE: To assess the reliability of magnetic resonance imaging (MRI for detection of esophageal cancer in the Levrat model of end-to-side esophagojejunostomy. BACKGROUND: The Levrat model has proven utility in terms of its ability to replicate Barrett's carcinogenesis by inducing gastroduodenoesophageal reflux (GDER. Due to lack of data on the utility of non-invasive methods for detection of esophageal cancer, treatment efficacy studies have been limited, as adenocarcinoma histology has only been validated post-mortem. It would therefore be of great value if the validity and reliability of MRI could be established in this setting. METHODS: Chronic GDER reflux was induced in 19 male Sprague-Dawley rats using the modified Levrat model. At 40 weeks post-surgery, all animals underwent endoscopy, MRI scanning, and post-mortem histological analysis of the esophagus and anastomosis. With post-mortem histology serving as the gold standard, assessment of presence of esophageal cancer was made by five esophageal specialists and five radiologists on endoscopy and MRI, respectively. RESULTS: The accuracy of MRI and endoscopic analysis to correctly identify cancer vs. no cancer was 85.3% and 50.5%, respectively. ROC curves demonstrated that MRI rating had an AUC of 0.966 (p<0.001 and endoscopy rating had an AUC of 0.534 (p = 0.804. The sensitivity and specificity of MRI for identifying cancer vs. no-cancer was 89.1% and 80% respectively, as compared to 45.5% and 57.5% for endoscopy. False positive rates of MRI and endoscopy were 20% and 42.5%, respectively. CONCLUSIONS: MRI is a more reliable diagnostic method than endoscopy in the Levrat model. The non-invasiveness of the tool and its potential to volumetrically quantify the size and number of tumors likely makes it even more useful in evaluating novel agents and their efficacy in treatment studies of esophageal cancer.

  12. The establishment and evaluation of a new model for the prediction of prostate cancer

    Wang, Qi; Li, Yan-Feng; Jiang, Jun; Zhang, Yong; Liu, Xu-Dong; Li, Ke

    2017-01-01

    Abstract To develop a new prostate cancer predictor (PCP) model using the combination of total prostate-specific antigen (tPSA), free PSA (fPSA), and complexed PSA (cPSA). The diagnoses of all the included patients were confirmed pathologically in Daping Hospital between December 1, 2011 and December 1, 2014. There were 54 PCa cases and 579 benign prostatic hyperplasia (BPH) cases with tPSA levels of 2 to 10?ng/mL, and 48 PCa cases and 147 BPH cases with tPSA levels of 10 to 20?ng/mL. Logisti...

  13. Establishment and characterization of a novel murine model of pancreatic cancer cachexia.

    Michaelis, Katherine A; Zhu, Xinxia; Burfeind, Kevin G; Krasnow, Stephanie M; Levasseur, Peter R; Morgan, Terry K; Marks, Daniel L

    2017-10-01

    Cachexia is a complex metabolic and behavioural syndrome lacking effective therapies. Pancreatic ductal adenocarcinoma (PDAC) is one of the most important conditions associated with cachexia, with >80% of PDAC patients suffering from the condition. To establish the cardinal features of a murine model of PDAC-associated cachexia, we characterized the effects of implanting a pancreatic tumour cell line from a syngeneic C57BL/6 KRAS G12D P53 R172H Pdx-Cre +/+ (KPC) mouse. Male and female C57BL/6 mice were inoculated subcutaneously, intraperitoneally, or orthotopically with KPC tumour cells. We performed rigorous phenotypic, metabolic, and behavioural analysis of animals over the course of tumour development. All routes of administration produced rapidly growing tumours histologically consistent with moderate to poorly differentiated PDAC. The phenotype of this model was dependent on route of administration, with orthotopic and intraperitoneal implantation inducing more severe cachexia than subcutaneous implantation. KPC tumour growth decreased food intake, decreased adiposity and lean body mass, and decreased locomotor activity. Muscle catabolism was observed in both skeletal and cardiac muscles, but the dominant catabolic pathway differed between these tissues. The wasting syndrome in this model was accompanied by hypothalamic inflammation, progressively decreasing brown and white adipose tissue uncoupling protein 1 (Ucp1) expression, and increased peripheral inflammation. Haematological and endocrine abnormalities included neutrophil-dominant leukocytosis and anaemia, and decreased serum testosterone. Syngeneic KPC allografts are a robust model for studying cachexia, which recapitulate key features of the PDAC disease process and induce a wide array of cachexia manifestations. This model is therefore ideally suited for future studies exploring the physiological systems involved in cachexia and for preclinical studies of novel therapies. © 2017 The Authors. Journal

  14. [Using (1)H-nuclear magnetic resonance metabolomics and gene ontology to establish pathological staging model for esophageal cancer patients].

    Chen, X; Wang, K; Chen, W; Jiang, H; Deng, P C; Li, Z J; Peng, J; Zhou, Z Y; Yang, H; Huang, G X; Zeng, J

    2016-07-01

    (ethanol amine, hydroxy-propionic acid, homocysteine and estriol) were eventually selected. gene ontology analysis showed that 54 enzymes and genes regulated the 4 key metabolic markers. The quantitative prediction model of esophageal cancer staging based on esophageal cancer NMR spectrum were established. Cross-validation results showed that the predicted effect was good (root mean square error=5.3, R(2)=0.47, P=0.036). The systems biology approaches based on metabolomics and enzyme-gene regulatory network analysis can be used to quantify the metabolic network disturbance of patients with advanced esophageal cancer, and to predict preoperative clinical staging of esophageal cancer patients by plasma NMR metabolomics.

  15. Establishing an Iso-Compliant Modern Cancer-Biobank in a Developing Country: A Model for International Cooperation.

    Sughayer, Maher A; Souan, Lina

    2015-01-01

    King Hussein Cancer (KHCC) is a specialized cancer center that treats both adult and pediatric cancer patients from Jordan and the neighboring countries. KHCC is acknowledged as a leader in cancer treatment in the Middle East and its vision is to maintain its leading position in cancer therapy and research. Hence, KHCC embarked on establishing the first ISO compliant cancer biobank (KHCCBIO) in Jordan.Currently, there are very few biobanks in the Middle East, hence, KHCC wanted to change this situation by establishing an ISO-compliant cancer biobank which would incorporate all current international guidelines and best-in class practices under an approved quality management system for the benefit of researchers in Jordan, its neighboring countries, and throughout the world. The established biobank would follow the highest ethical standards in collecting, processing, storing and distributing high-quality, clinically annotated biospecimens.The strategy used in establishing KHCCBIO was based on taking advantage of international networking and collaboration. This in essence led to knowledge transfer between well established organizations, institutions and individuals from Europe and Jordan, in existing technological innovation and internationally recognized quality standards. KHCC efforts were facilitated by a grant from the European Union under the seventh frame work program.Future aims of KHCCBIO are to develop KHCC's research infrastructure, increase its scope and visibility and improve its competitiveness throughout the biomedical science arena. Moreover, KHCCBIO is aiming to establish a platform for future knowledge transfer and collaborative research; develop partnerships between European and Middle Eastern organizations.

  16. The establishment of transmissible venereal tumor lung cancer model in canine and the observation of its biological characteristics

    Sun Zhichao; Dong Weihua; Xiao Xiangsheng; Zhu Ruimin; Chen mofan; Wang Zhi

    2010-01-01

    Objective: To establish an allogeneic transplanted lung cancer model in canine by percutaneously injecting canine transmissible venereal tumor (CTVT) cell suspension and to observe its biological characteristics. Methods: Under CT guidance fresh CTVT cell suspension was inoculated into the middle or posterior lobe of lungs through percutaneous puncturing needle in 12 beagle dogs. Cyclosporin was administrated orally to obtain immunosuppression. Tumor growth and metastasis were judged by chest CT scanning at regular intervals (every 1-2 weeks). The daily mental and physical condition of the dogs was observed. Autopsy and pathological examination were performed when the animals died naturally or at the tenth week after the procedure when the animals were sacrificed. Results: A total of 15 sites were inoculated in 12 dogs. The formation of tumor was observed in 2 dogs at the fifth week and in 9 dogs at the sixth week. Ten weeks after the inoculation the formation of tumor was detected in 10 inoculated points in 9 dogs, the inoculation success rate was 66.67%. The mean largest diameter of the tumor at 6, 8 and 10 weeks after the inoculation was (1.059 ± 0.113)cm, (1.827 ± 0.084)cm and (2.189 ± 0.153)cm, respectively. The largest diameter of the tumor nodule was 3.5 cm. Moderate to severe pleural effusion and mediastinal lymph nodes metastasis were found in all the dogs that showed the formation of the tumor. Conclusion: Percutaneous CTVT cell suspension injection can establish an allogeneic canine lung cancer model, which is helpful for the experimental studies related to lung cancer. (authors)

  17. Elucidating the T-cell reactivity against porcine IDO and RhoC to establish the pig as an animal model for vaccine development against human cancer

    Overgaard, Nana Haahr; Frøsig, Thomas Mørch; Welner, Simon

    therapies against cancer, vaccine formulations tailored to mount in vivo CTL responses towards co-delivered cancer antigens will be an important hallmark. Recognition of antigen-derived peptides presented in the context of major histocompatibility complex (MHC) class I molecules on cancer cells......Immune therapy of cancer has recently experienced a great breakthrough with prolonged overall survival in patients with metastatic disease following the use of checkpoint inhibitors and T cell therapy with ex vivo expanded CD8+ cytotoxic T cells (CTLs). In the further development of immune...... is a requirement for activation of CTLs. Previously, the development of therapeutic anti-cancer vaccines have largely been based on rodent models, in particular mice; however the majority of these fail to establish a therapeutic response once put into clinical trials. Pigs have the potential of serving as a model...

  18. Establishment and Characterization of a Highly Tumourigenic and Cancer Stem Cell Enriched Pancreatic Cancer Cell Line as a Well Defined Model System

    Fredebohm, Johannes; Boettcher, Michael; Eisen, Christian; Gaida, Matthias M.; Heller, Anette; Keleg, Shereen; Tost, Jörg; Greulich-Bode, Karin M.; Hotz-Wagenblatt, Agnes; Lathrop, Mark; Giese, Nathalia A.; Hoheisel, Jörg D.

    2012-01-01

    Standard cancer cell lines do not model the intratumoural heterogeneity situation sufficiently. Clonal selection leads to a homogeneous population of cells by genetic drift. Heterogeneity of tumour cells, however, is particularly critical for therapeutically relevant studies, since it is a prerequisite for acquiring drug resistance and reoccurrence of tumours. Here, we report the isolation of a highly tumourigenic primary pancreatic cancer cell line, called JoPaca-1 and its detailed characterization at multiple levels. Implantation of as few as 100 JoPaca-1 cells into immunodeficient mice gave rise to tumours that were histologically very similar to the primary tumour. The high heterogeneity of JoPaca-1 was reflected by diverse cell morphology and a substantial number of chromosomal aberrations. Comparative whole-genome sequencing of JoPaca-1 and BxPC-3 revealed mutations in genes frequently altered in pancreatic cancer. Exceptionally high expression of cancer stem cell markers and a high clonogenic potential in vitro and in vivo was observed. All of these attributes make this cell line an extremely valuable model to study the biology of and pharmaceutical effects on pancreatic cancer. PMID:23152778

  19. Establishing the isolated Standard Model

    Wells, James D.; Zhang, Zhengkang; Zhao, Yue

    2017-02-01

    The goal of this article is to initiate a discussion on what it takes to claim ''there is no new physics at the weak scale,'' namely that the Standard Model (SM) is ''isolated.'' The lack of discovery of beyond the SM (BSM) physics suggests that this may be the case. But to truly establish this statement requires proving all ''connected'' BSM theories are false, which presents a significant challenge. We propose a general approach to quantitatively assess the current status and future prospects of establishing the isolated SM (ISM), which we give a reasonable definition of. We consider broad elements of BSM theories, and show many examples where current experimental results are not sufficient to verify the ISM. In some cases, there is a clear roadmap for the future experimental program, which we outline, while in other cases, further efforts - both theoretical and experimental - are needed in order to robustly claim the establishment of the ISM in the absence of new physics discoveries.

  20. Establishing the isolated Standard Model

    Wells, James D.; Zhang, Zhengkang [Michigan Univ., Ann Arbor, MI (United States). Michigan Center for Theoretical Physics; Deutsches Elektronen-Synchrotron (DESY), Hamburg (Germany); Zhao, Yue [Michigan Univ., Ann Arbor, MI (United States). Michigan Center for Theoretical Physics

    2017-02-15

    The goal of this article is to initiate a discussion on what it takes to claim ''there is no new physics at the weak scale,'' namely that the Standard Model (SM) is ''isolated.'' The lack of discovery of beyond the SM (BSM) physics suggests that this may be the case. But to truly establish this statement requires proving all ''connected'' BSM theories are false, which presents a significant challenge. We propose a general approach to quantitatively assess the current status and future prospects of establishing the isolated SM (ISM), which we give a reasonable definition of. We consider broad elements of BSM theories, and show many examples where current experimental results are not sufficient to verify the ISM. In some cases, there is a clear roadmap for the future experimental program, which we outline, while in other cases, further efforts - both theoretical and experimental - are needed in order to robustly claim the establishment of the ISM in the absence of new physics discoveries.

  1. Establishment and characterization of models of chemotherapy resistance in colorectal cancer: Towards a predictive signature of chemoresistance

    Jensen, Niels F.; Stenvang, Jan; Beck, Mette Kristina

    2015-01-01

    Current standard treatments for metastatic colorectal cancer (CRC) are based on combination regimens with one of the two chemotherapeutic drugs, irinotecan or oxaliplatin. However, drug resistance frequently limits the clinical efficacy of these therapies. In order to gain new insights into mecha...

  2. Mouse Model of Devil Facial Tumour Disease establishes that an effective immune response can be generated against the cancer cells

    Terry L Pinfold

    2014-05-01

    Full Text Available The largest carnivorous marsupial in Australia, the Tasmanian devil (Sarcophilus harrisii is facing extinction in the wild due to a transmissible cancer known as Devil Facial Tumour Disease (DFTD. DFTD is a clonal cell line transmitted from host to host with 100% mortality and no known immunity. While it was first considered that low genetic diversity of the population of devils enabled the allograft transmission of DFTD recent evidence reveals that genetically diverse animals succumb to the disease. The lack of an immune response against the DFTD tumor cells may be due to a lack of immunogenicity of the tumor cells. This could facilitate transmission between devils. To test immunogenicity, mice were injected with viable DFTD cells and anti-DFTD immune responses analyzed. A range of antibody isotypes against DFTD cells was detected, indicating that as DFTD cells can induce an immune response they are immunogenic. This was supported by cytokine production, when splenocytes from mice injected with DFTD cells were cultured in vitro with DFTD cells and the supernatant analyzed. There was a significant production of IFN-γ and TNF-α following the first injection with DFTD cells and a significant production of IL-6 and IL-10 following the second injection. Splenocytes from naïve or immunized mice killed DFTD cells in in vitro cytotoxicity assays. Thus they are also targets for immunological destruction. We conclude that as an immune response can be generated against DFTD cells they would be suitable targets for a vaccine.

  3. Establishment and validation of a predictive nomogram model for non-small cell lung cancer patients with chronic hepatitis B viral infection.

    Chen, Shulin; Lai, Yanzhen; He, Zhengqiang; Li, Jianpei; He, Xia; Shen, Rui; Ding, Qiuying; Chen, Hao; Peng, Songguo; Liu, Wanli

    2018-05-04

    This study aimed to establish an effective predictive nomogram for non-small cell lung cancer (NSCLC) patients with chronic hepatitis B viral (HBV) infection. The nomogram was based on a retrospective study of 230 NSCLC patients with chronic HBV infection. The predictive accuracy and discriminative ability of the nomogram were determined by a concordance index (C-index), calibration plot and decision curve analysis and were compared with the current tumor, node, and metastasis (TNM) staging system. Independent factors derived from Kaplan-Meier analysis of the primary cohort to predict overall survival (OS) were all assembled into a Cox proportional hazards regression model to build the nomogram model. The final model included age, tumor size, TNM stage, treatment, apolipoprotein A-I, apolipoprotein B, glutamyl transpeptidase and lactate dehydrogenase. The calibration curve for the probability of OS showed that the nomogram-based predictions were in good agreement with the actual observations. The C-index of the model for predicting OS had a superior discrimination power compared with the TNM staging system [0.780 (95% CI 0.733-0.827) vs. 0.693 (95% CI 0.640-0.746), P  20.0). The proposed nomogram model resulted in more accurate prognostic prediction for NSCLC patients with chronic HBV infection.

  4. Multiscale Cancer Modeling

    Macklin, Paul; Cristini, Vittorio

    2013-01-01

    Simulating cancer behavior across multiple biological scales in space and time, i.e., multiscale cancer modeling, is increasingly being recognized as a powerful tool to refine hypotheses, focus experiments, and enable more accurate predictions. A growing number of examples illustrate the value of this approach in providing quantitative insight on the initiation, progression, and treatment of cancer. In this review, we introduce the most recent and important multiscale cancer modeling works that have successfully established a mechanistic link between different biological scales. Biophysical, biochemical, and biomechanical factors are considered in these models. We also discuss innovative, cutting-edge modeling methods that are moving predictive multiscale cancer modeling toward clinical application. Furthermore, because the development of multiscale cancer models requires a new level of collaboration among scientists from a variety of fields such as biology, medicine, physics, mathematics, engineering, and computer science, an innovative Web-based infrastructure is needed to support this growing community. PMID:21529163

  5. Establishing model credibility involves more than validation

    Kirchner, T.

    1991-01-01

    One widely used definition of validation is that the quantitative test of the performance of a model through the comparison of model predictions to independent sets of observations from the system being simulated. The ability to show that the model predictions compare well with observations is often thought to be the most rigorous test that can be used to establish credibility for a model in the scientific community. However, such tests are only part of the process used to establish credibility, and in some cases may be either unnecessary or misleading. Naylor and Finger extended the concept of validation to include the establishment of validity for the postulates embodied in the model and the test of assumptions used to select postulates for the model. Validity of postulates is established through concurrence by experts in the field of study that the mathematical or conceptual model contains the structural components and mathematical relationships necessary to adequately represent the system with respect to the goals for the model. This extended definition of validation provides for consideration of the structure of the model, not just its performance, in establishing credibility. Evaluation of a simulation model should establish the correctness of the code and the efficacy of the model within its domain of applicability. (24 refs., 6 figs.)

  6. Establishing statistical models of manufacturing parameters

    Senevat, J.; Pape, J.L.; Deshayes, J.F.

    1991-01-01

    This paper reports on the effect of pilgering and cold-work parameters on contractile strain ratio and mechanical properties that were investigated using a large population of Zircaloy tubes. Statistical models were established between: contractile strain ratio and tooling parameters, mechanical properties (tensile test, creep test) and cold-work parameters, and mechanical properties and stress-relieving temperature

  7. Establishing a family risk assessment clinic for breast cancer.

    Mulsow, Jurgen

    2012-02-01

    Breast cancer is the most common cancer affecting European women and the leading cause of cancer-related death. A total of 15-20% of women who develop breast cancer have a family history and 5-10% a true genetic predisposition. The identification and screening of women at increased risk may allow early detection of breast cancer and improve prognosis. We established a family risk assessment clinic in May 2005 to assess and counsel women with a family history of breast cancer, to initiate surveillance, and to offer risk-reducing strategies for selected high-risk patients. Patients at medium or high risk of developing breast cancer according to NICE guidelines were accepted. Family history was determined by structured questionnaire and interview. Lifetime risk of developing breast cancer was calculated using Claus and Tyrer-Cuzick scoring. Risk of carrying a breast cancer-related gene mutation was calculated using the Manchester system. One thousand two hundred and forty-three patients have been referred. Ninety-two percent were at medium or high risk of developing breast cancer. Formal assessment of risk has been performed in 368 patients, 73% have a high lifetime risk of developing breast cancer, and 72% a Manchester score >or=16. BRCA1\\/2 mutations have been identified in 14 patients and breast cancer diagnosed in two. Our initial experience of family risk assessment has shown there to be a significant demand for this service. Identification of patients at increased risk of developing breast cancer allows us to provide individuals with accurate risk profiles, and enables patients to make informed choices regarding their follow-up and management.

  8. Establishing a Cancer Genetics Programme in Asia - the Singapore Experience

    Chieng Wei-Shieng

    2006-06-01

    Full Text Available Abstract Cancer genetics is now an established oncology subspecialty with the primary prevention role of identifying high-risk individuals through genetic information for enrolment into screening and preventive programmes. Integrated into major Western centres since the late 1990s, such a programme has been established in Singapore since 2001. Our programme has evaluated 367 index patients comprising mainly breast and colorectal cancer cases. Cancer patients were receptive to genetic counselling, but cost posed a major barrier to genetic testing. However, when the cost barrier was removed through government subsidy plans, more than half of high-risk patients still declined testing. The major barriers were reluctance to involve family members, perception that the information would not change management, and fears of negative feelings. Confirmed mutation carriers were compliant to screening and receptive to prophylactic surgery. Uptake of predictive testing among cancer-free family members has been low, possibly arising from the stigma associated with cancer in our Asian culture. These potential barriers are being addressed through government subsidy plans, continuing education to increase awareness, and being culturally sensitive when dealing with the Asian family.

  9. 3D Hanging Drop Culture to Establish Prostate Cancer Organoids.

    Eder, Theresa; Eder, Iris E

    2017-01-01

    Three-dimensional (3D) cell culture enables the growth of cells in a multidimensional and multicellular manner compared to conventional cell culture techniques. Especially in prostate cancer research there is a big need for more tissue-recapitulating models to get a better understanding of the mechanisms driving prostate cancer as well as to screen for more efficient drugs that can be used for treatment. In this chapter we describe a 3D hanging drop system that can be used to culture prostate cancer organoids as tumor epithelial monocultures and as epithelial-stromal cocultures.

  10. Establishing an International Soil Modelling Consortium

    Vereecken, Harry; Schnepf, Andrea; Vanderborght, Jan

    2015-04-01

    Soil is one of the most critical life-supporting compartments of the Biosphere. Soil provides numerous ecosystem services such as a habitat for biodiversity, water and nutrients, as well as producing food, feed, fiber and energy. To feed the rapidly growing world population in 2050, agricultural food production must be doubled using the same land resources footprint. At the same time, soil resources are threatened due to improper management and climate change. Soil is not only essential for establishing a sustainable bio-economy, but also plays a key role also in a broad range of societal challenges including 1) climate change mitigation and adaptation, 2) land use change 3) water resource protection, 4) biotechnology for human health, 5) biodiversity and ecological sustainability, and 6) combating desertification. Soils regulate and support water, mass and energy fluxes between the land surface, the vegetation, the atmosphere and the deep subsurface and control storage and release of organic matter affecting climate regulation and biogeochemical cycles. Despite the many important functions of soil, many fundamental knowledge gaps remain, regarding the role of soil biota and biodiversity on ecosystem services, the structure and dynamics of soil communities, the interplay between hydrologic and biotic processes, the quantification of soil biogeochemical processes and soil structural processes, the resilience and recovery of soils from stress, as well as the prediction of soil development and the evolution of soils in the landscape, to name a few. Soil models have long played an important role in quantifying and predicting soil processes and related ecosystem services. However, a new generation of soil models based on a whole systems approach comprising all physical, mechanical, chemical and biological processes is now required to address these critical knowledge gaps and thus contribute to the preservation of ecosystem services, improve our understanding of climate

  11. Establishment of Cancer Stem Cell Cultures from Human Conventional Osteosarcoma.

    Palmini, Gaia; Zonefrati, Roberto; Mavilia, Carmelo; Aldinucci, Alessandra; Luzi, Ettore; Marini, Francesca; Franchi, Alessandro; Capanna, Rodolfo; Tanini, Annalisa; Brandi, Maria Luisa

    2016-10-14

    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.

  12. Modeling Human Cancers in Drosophila.

    Sonoshita, M; Cagan, R L

    2017-01-01

    Cancer is a complex disease that affects multiple organs. Whole-body animal models provide important insights into oncology that can lead to clinical impact. Here, we review novel concepts that Drosophila studies have established for cancer biology, drug discovery, and patient therapy. Genetic studies using Drosophila have explored the roles of oncogenes and tumor-suppressor genes that when dysregulated promote cancer formation, making Drosophila a useful model to study multiple aspects of transformation. Not limited to mechanism analyses, Drosophila has recently been showing its value in facilitating drug development. Flies offer rapid, efficient platforms by which novel classes of drugs can be identified as candidate anticancer leads. Further, we discuss the use of Drosophila as a platform to develop therapies for individual patients by modeling the tumor's genetic complexity. Drosophila provides both a classical and a novel tool to identify new therapeutics, complementing other more traditional cancer tools. © 2017 Elsevier Inc. All rights reserved.

  13. Mouse Models of Gastric Cancer

    Hayakawa, Yoku; Fox, James G.; Gonda, Tamas; Worthley, Daniel L.; Muthupalani, Sureshkumar; Wang, Timothy C.

    2013-01-01

    Animal models have greatly enriched our understanding of the molecular mechanisms of numerous types of cancers. Gastric cancer is one of the most common cancers worldwide, with a poor prognosis and high incidence of drug-resistance. However, most inbred strains of mice have proven resistant to gastric carcinogenesis. To establish useful models which mimic human gastric cancer phenotypes, investigators have utilized animals infected with Helicobacter species and treated with carcinogens. In addition, by exploiting genetic engineering, a variety of transgenic and knockout mouse models of gastric cancer have emerged, such as INS-GAS mice and TFF1 knockout mice. Investigators have used the combination of carcinogens and gene alteration to accelerate gastric cancer development, but rarely do mouse models show an aggressive and metastatic gastric cancer phenotype that could be relevant to preclinical studies, which may require more specific targeting of gastric progenitor cells. Here, we review current gastric carcinogenesis mouse models and provide our future perspectives on this field. PMID:24216700

  14. Repurposing Established Compounds to Target Pancreatic Cancer Stem Cells (CSCs

    Bernhard W. Renz

    2017-06-01

    Full Text Available The diagnosis of pancreatic ductal adenocarcinoma (PDAC carries a dismal prognosis, in particular, when patients present with unresectable disease. While significant progress has been made in understanding the biology of PDAC, this knowledge has not translated into a clear clinical benefit and current chemotherapeutic strategies only offer a modest improvement in overall survival. Accordingly, novel approaches are desperately needed. One hypothesis that could—at least in part—explain the desolate response of PDAC to chemotherapy is the so-called cancer stem cell (CSC concept, which attributes specific traits, such as chemoresistance, metastatic potential and a distinct metabolism to a small cellular subpopulation of the whole tumor. At the same time, however, some of these attributes could make CSCs more permissive for novel therapeutic strategies with compounds that are already in clinical use. Most recently, several publications have tried to enlighten the field with the idea of repurposing established drugs for antineoplastic use. As such, recycling drugs could present an intriguing and fast-track method with new therapeutic paradigms in anti-cancer and anti-CSC treatments. Here, we aim to summarize important aspects and novel findings of this emerging field.

  15. Establishment of the Fox Chase Network Breast Cancer Risk Registry

    Daly, Mary

    1997-01-01

    .... The development of the Fox Chase Cancer Center Breast Cancer Risk Registry was proposed to facilitate research in the epidemiologic and genetic predictors of disease and will permit evaluation...

  16. Establishment of a tumor neovascularization animal model with biomaterials in rabbit corneal pouch.

    Chu, Yu-Ping; Li, Hong-Chuan; Ma, Ling; Xia, Yang

    2018-06-01

    The present animal model of tumor neovascularization most often used by researchers is zebrafish. For studies on human breast cancer cell neovascularization, a new animal model was established to enable a more convenient study of tumor neovascularization. A sodium alginate-gelatin blend gel system was used to design the new animal model. The model was established using rabbit corneal pouch implantation. Then, the animal model was validated by human breast cancer cell lines MCF-7-Kindlin-2 and MCF-7-CMV. The experiment intuitively observed the relationship between tumor and neovascularization, and demonstrated the advantages of this animal model in the study of tumor neovascularization. The use of sodium alginate-gelatin blends to establish tumor neovascularization in a rabbit corneal pouch is a novel and ideal method for the study of neovascularization. It may be a better animal model for expanding the research in this area. Copyright © 2018 Elsevier Inc. All rights reserved.

  17. Establishment and conventional cytogenetic characterization of three gastric cancer cell lines.

    Leal, Mariana Ferreira; Martins do Nascimento, José Luiz; da Silva, Carla Elvira Araújo; Vita Lamarão, Maria Fernanda; Calcagno, Danielle Queiroz; Khayat, André Salim; Assumpção, Paulo Pimentel; Cabral, Isabel Rosa; de Arruda Cardoso Smith, Marília; Burbano, Rommel Rodríguez

    2009-11-01

    Gastric cancer is the fourth most frequent type of cancer and the second most frequent cause of cancer mortality worldwide. Only a modest number of gastric carcinoma cell lines have been isolated thus far. Here we describe the establishment and cytogenetic characterization of three new gastric cancer cell lines obtained from primary gastric adenocarcinoma (ACP02 and ACP03) and cancerous ascitic fluid (AGP01) of individuals from northern Brazil. ACP02, ACP03, and AGP01 cell lines are presently in the 60th passage. The cell lines grew in a disorganized single layer with some agglomerations and heterogeneous divisions (bipolar and multipolar). All cell lines exhibited a composite karyotype with several clonal chromosome alterations. Trisomy 8 was the most frequent alteration. Chromosome 8 aneusomy was confirmed by fluorescence in situ hybridization. All cell lines also exhibited trisomy 7 and deletion of chromosome arm 17p. These results suggest that, although frequent chromosome alterations are commonly observed due to culture process, the ACP02, ACP03, and AGP01 cell lines and primary gastric cancer from individuals of northern Brazil share genetic alterations, supporting use of these cell lines as a model of gastric carcinogenesis in this population.

  18. Neoadjuvant Therapy for Breast Cancer : Established Concepts and Emerging Strategies

    Steenbruggen, Tessa G; van Ramshorst, Mette S.; Kok, Marleen; Linn, Sabine C.; Smorenburg, Carolien H.; Sonke, Gabe S

    2017-01-01

    In the last decade, the systemic treatment approach for patients with early breast cancer has partly shifted from adjuvant treatment to neoadjuvant treatment. Systemic treatment administration started as a ‘one size fits all’ approach but is currently customized according to each breast cancer

  19. Targeted sequencing of established and candidate colorectal cancer genes in the Colon Cancer Family Registry Cohort.

    Raskin, Leon; Guo, Yan; Du, Liping; Clendenning, Mark; Rosty, Christophe; Lindor, Noralane M; Gruber, Stephen B; Buchanan, Daniel D

    2017-11-07

    The underlying genetic cause of colorectal cancer (CRC) can be identified for 5-10% of all cases, while at least 20% of CRC cases are thought to be due to inherited genetic factors. Screening for highly penetrant mutations in genes associated with Mendelian cancer syndromes using next-generation sequencing (NGS) can be prohibitively expensive for studies requiring large samples sizes. The aim of the study was to identify rare single nucleotide variants and small indels in 40 established or candidate CRC susceptibility genes in 1,046 familial CRC cases (including both MSS and MSI-H tumor subtypes) and 1,006 unrelated controls from the Colon Cancer Family Registry Cohort using a robust and cost-effective DNA pooling NGS strategy. We identified 264 variants in 38 genes that were observed only in cases, comprising either very rare (minor allele frequency cancer susceptibility genes BAP1, CDH1, CHEK2, ENG, and MSH3 . For the candidate CRC genes, we identified likely pathogenic variants in the helicase domain of POLQ and in the LRIG1 , SH2B3 , and NOS1 genes and present their clinicopathological characteristics. Using a DNA pooling NGS strategy, we identified novel germline mutations in established CRC susceptibility genes in familial CRC cases. Further studies are required to support the role of POLQ , LRIG1 , SH2B3 and NOS1 as CRC susceptibility genes.

  20. Breast Cancer Methylomes Establish an Epigenomic Foundation for Metastasis

    Fang, Fang; Turcan, Sevin; Rimner, Andreas; Kaufman, Andrew; Giri, Dilip; Morris, Luc G. T.; Shen, Ronglai; Seshan, Venkatraman; Mo, Qianxing; Heguy, Adriana; Baylin, Stephen B.; Ahuja, Nita; Viale, Agnes; Massague, Joan; Norton, Larry; Vahdat, Linda T.; Moynahan, Mary Ellen; Chan, Timothy A.

    2011-01-01

    Cancer-specific alterations in DNA methylation are hallmarks of human malignancies; however, the nature of the breast cancer epigenome and its effects on metastatic behavior remain obscure. To address this issue, we used genome-wide analysis to characterize the methylomes of breast cancers with diverse metastatic behavior. Groups of breast tumors were characterized by the presence or absence of coordinate hypermethylation at a large number of genes, demonstrating a breast CpG island methylator phenotype (B-CIMP). The B-CIMP provided a distinct epigenomic profile and was a strong determinant of metastatic potential. Specifically, the presence of the B-CIMP in tumors was associated with low metastatic risk and survival, and the absence of the B-CIMP was associated with high metastatic risk and death. B-CIMP loci were highly enriched for genes that make up the metastasis transcriptome. Methylation at B-CIMP genes accounted for much of the transcriptomal diversity between breast cancers of varying prognosis, indicating a fundamental epigenomic contribution to metastasis. Comparison of the loci affected by the B-CIMP with those affected by the hypermethylator phenotype in glioma and colon cancer revealed that the CIMP signature was shared by multiple human malignancies. Our data provide a unifying epigenomic framework linking breast cancers with varying outcome and transcriptomic changes underlying metastasis. These findings significantly enhance our understanding of breast cancer oncogenesis and aid the development of new prognostic biomarkers for this common malignancy. PMID:21430268

  1. Spherical Cancer Models in Tumor Biology

    Louis-Bastien Weiswald

    2015-01-01

    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.

  2. Characterization of newly established colorectal cancer cell lines ...

    Unknown

    2000-12-19

    Dec 19, 2000 ... ... Medicine, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, NY 10021, USA .... with biotinylated horse anti-mouse IgG (Vector Labora- ...... development of new therapies or prognosis of the disease,.

  3. Establishment of the Fox Chase Network Breast Cancer Risk Registry

    1996-10-01

    related to caner also are d ed. breast cancer. Participants learn about screening guidelines and prevention options. The Cancer Center Eligibility...ever treated with a series of x-rays to the front of your neck for acne, neck tumor or any other reason? (This does not include routine screening x-rays...hysterectomy (surgical removal of the uterus )? 10] Yes CONTINUE 20 No CONTINUE 80 Don’t know CONTINUE a. If yes, how old were you? (-) years 10. Have

  4. Chapter 4: Establishment of the integrated modelling system

    1995-01-01

    This chapter summarizes how the Integrated Modelling System has been established. The Danubian Lowland Information System (DLIS) has been developed, providing a central database and Geographical Information System (GIS) with facilities for data storage, maintenance, processing and presentation. In addition, data can be imported and exported in the file formats readable for the applied modelling system

  5. Comparison of 4 established DASH diet indexes: examining associations of index scores and colorectal cancer.

    Miller, Paige E; Cross, Amanda J; Subar, Amy F; Krebs-Smith, Susan M; Park, Yikyung; Powell-Wiley, Tiffany; Hollenbeck, Albert; Reedy, Jill

    2013-09-01

    Multiple diet indexes have been developed to capture the Dietary Approaches to Stop Hypertension (DASH) dietary pattern and examine relations with health outcomes but have not been compared within the same study population to our knowledge. We compared 4 established DASH indexes and examined associations with colorectal cancer. Scores were generated from a food-frequency questionnaire in the NIH-AARP Diet and Health Study (n = 491,841). Separate indexes defined by Dixon (7 food groups, saturated fat, and alcohol), Mellen (9 nutrients), Fung (7 food groups and sodium), and Günther (8 food groups) were used. HRs and 95% CIs for colorectal cancer were generated by using Cox proportional hazard models. From 1995 through 2006, 6752 incident colorectal cancer cases were ascertained. In men, higher scores were associated with reduced colorectal cancer incidence by comparing highest to lowest quintiles for all indexes as follows: Dixon (HR: 0.77; 95% CI: 0.69, 0.87), Mellen (HR: 0.78; 95% CI: 0.71, 0.86), Fung (HR: 0.75; 95% CI: 0.68, 0.83), and Günther (HR: 0.81; 95% CI: 0.74, 0.90). Higher scores in women were inversely associated with colorectal cancer incidence by using methods defined by Mellen (HR: 0.79; 95% CI: 0.68, 0.91), Fung (HR: 0.84; 95% CI: 0.73, 0.96), and Günther (HR: 0.84; 95% CI: 0.73.0.97) but not Dixon (HR: 1.01; 95% CI: 0.80, 1.28). The consistency in findings, particularly in men, suggests that all indexes capture an underlying construct inherent in the DASH dietary pattern, although the specific index used can affect results.

  6. Comparison of 4 established DASH diet indexes: examining associations of index scores and colorectal cancer123

    Cross, Amanda J; Subar, Amy F; Krebs-Smith, Susan M; Park, Yikyung; Powell-Wiley, Tiffany; Hollenbeck, Albert; Reedy, Jill

    2013-01-01

    Background: Multiple diet indexes have been developed to capture the Dietary Approaches to Stop Hypertension (DASH) dietary pattern and examine relations with health outcomes but have not been compared within the same study population to our knowledge. Objective: We compared 4 established DASH indexes and examined associations with colorectal cancer. Design: Scores were generated from a food-frequency questionnaire in the NIH-AARP Diet and Health Study (n = 491,841). Separate indexes defined by Dixon (7 food groups, saturated fat, and alcohol), Mellen (9 nutrients), Fung (7 food groups and sodium), and Günther (8 food groups) were used. HRs and 95% CIs for colorectal cancer were generated by using Cox proportional hazard models. Results: From 1995 through 2006, 6752 incident colorectal cancer cases were ascertained. In men, higher scores were associated with reduced colorectal cancer incidence by comparing highest to lowest quintiles for all indexes as follows: Dixon (HR: 0.77; 95% CI: 0.69, 0.87), Mellen (HR: 0.78; 95% CI: 0.71, 0.86), Fung (HR: 0.75; 95% CI: 0.68, 0.83), and Günther (HR: 0.81; 95% CI: 0.74, 0.90). Higher scores in women were inversely associated with colorectal cancer incidence by using methods defined by Mellen (HR: 0.79; 95% CI: 0.68, 0.91), Fung (HR: 0.84; 95% CI: 0.73, 0.96), and Günther (HR: 0.84; 95% CI: 0.73.0.97) but not Dixon (HR: 1.01; 95% CI: 0.80, 1.28). Conclusion: The consistency in findings, particularly in men, suggests that all indexes capture an underlying construct inherent in the DASH dietary pattern, although the specific index used can affect results. PMID:23864539

  7. Establishment of modified reversible regional cerebral ischemic models

    Ji Xunming; Ling Feng; Zhao Xiqing; Xuan Yun; Wang Yueqin; Ling Xiaolan; Chang Hongjun; Zhang Zhiping

    2005-01-01

    Objective: Modifying the method of establishing reversible middle cerebral ischemic models in rats for improvement of the stability and rate of success, so as to raise the reliability of cerebral ischemic study. Methods: Sixty male Wistar rats were randomly divided into two groups, modified and control groups, 30 rats in each group. The method of silicone- tipping on one end of the nylon suture was used to modify the establishment of embolus, and tip-heating method was used to establish the traditional embolus with all the other steps of the procedure just the same. The Zea Longa 5 scoring scale was used to estimate the neurological deficiency while TTC staining method was used to measure and calculate the volume of cerebral infarction. The percentage of successful models with 3-4 grade scorings and the coefficient of the variations of cerebral infarct volume were used to estimate the stability of the models. Results: The rate of success of establishment models in the modification group was significantly higher in comparing with the traditional group (93% vs 60%, χ 2 =9.32, P=0.002). The percentage of model establishment with 3-4 grade neurological scores in modification group was higher than that in the traditional group 96.4% vs 61.2%, χ 2 =9.51, P=0.002). The cerebral infarct volume in modification group and traditional group were (4.1450±0.5019) cm 3 and (3.8435 ± 0.8164) cm 3 , and the coefficients of variation were 12.01% and 21.24% respectively, which indicated that the stability of models was significantly higher in modification group than in the traditional one. Conclusions: The rates of success and stability of the models for reversible focal cerebral ischemia made by the modification method were significantly improved, with decreasing the cost of model creation and increasing the accuracy of study of ischemic cerebral vascular disease. (authors)

  8. A Mathematical Approach to Establishing Constitutive Models for Geomaterials

    Guang-hua Yang

    2013-01-01

    Full Text Available The mathematical foundation of the traditional elastoplastic constitutive theory for geomaterials is presented from the mathematical point of view, that is, the expression of stress-strain relationship in principal stress/strain space being transformed to the expression in six-dimensional space. A new framework is then established according to the mathematical theory of vectors and tensors, which is applicable to establishing elastoplastic models both in strain space and in stress space. Traditional constitutive theories can be considered as its special cases. The framework also enables modification of traditional constitutive models.

  9. Optimal locations of establishing smoking cessation services for cancer patients in Crete, Greece

    Dimitra Sifaki-Pistolla

    2017-05-01

    The proposed optimum locations for establishing smoking cessation services are expected to contribute to the enhancement of cancer control in Crete. Furthermore, this study will guide a smoking cessation program in the region of Crete aiming to minimize the burden of tobacco-induced cancers.

  10. Dogs as a Model for Cancer.

    Gardner, Heather L; Fenger, Joelle M; London, Cheryl A

    2016-01-01

    Spontaneous cancers in client-owned dogs closely recapitulate their human counterparts with respect to clinical presentation, histological features, molecular profiles, and response and resistance to therapy, as well as the evolution of drug-resistant metastases. In several instances the incorporation of dogs with cancer into the preclinical development path of cancer therapeutics has influenced outcome by helping to establish pharmacokinetic/pharmacodynamics relationships, dose/regimen, expected clinical toxicities, and ultimately the potential for biologic activity. As our understanding regarding the molecular drivers of canine cancers has improved, unique opportunities have emerged to leverage this spontaneous model to better guide cancer drug development so that therapies likely to fail are eliminated earlier and therapies with true potential are optimized prior to human studies. Both pets and people benefit from this approach, as it provides dogs with access to cutting-edge cancer treatments and helps to insure that people are given treatments more likely to succeed.

  11. Discussion on the establishment of blood glucose fluctuation animal models

    Chun-Liu Gai; Jing-Ru Zhao; Xiao-Long Chen

    2014-01-01

    AIM: To provide the experimental basis for the in vivo study of blood glucose fluctuation injury mechanism, through intraperitoneal injection of glucose to establish blood glucose fluctuation animal models and to simulate blood glucose fluctuation of patients with diabetes.METHODS: Rats were randomly divided into four groups: normal control group(NC), normal fluctuation group(NF), diabetes mellitus group(DM)and diabetes fluctuation group(DF). Diabetic models were induced through intraperitone...

  12. Screening and Establishment of Human Lung Cancer Cell Lines 
with Organ-specific Metastasis Potential

    Qinghua ZHOU

    2014-03-01

    Full Text Available Background and objective Cancer metastasis is not only the malignant marker and characteristics, but also the main cause of failure to cure and lose their life in the patients with lung cancer. Lung cancer metastasis has organ-specific characteristics. The most common sites of lung cancer metastasis are mediastinal lymph node, brain, bone, liver and adrenal gland. The aim of this study is to screen and establish lung cancer cell model with organ-specific metastasis potential with human high-metastatic large cell lung cancer cell line L9981 established by our laboratory previously, and to provide cell models for studying the mechanisms and signal regulation of organ-specific metastasis of lung cancer. Materials and methods The parent lung cancer cell line, L9981-Luc, was inoculated in the armpit of nude mice. The live animal imaging system, IVIS-200, was used to detect the lung cancer organ-specific metastasis every week. When the organ-specific metastasis were established, the nude mices bearing the lung cancer were sacrificed when they became moribund. Under sterile conditions, the organs (mediastinal lymph nodes, lung, spinal column and brain with lung cancer organ-specific metastasis were removed and the metastasized nodules were dissected free of connective tissue and blood clots, and rinsed twice with medium. The metastasized nodules were finely minced using sterile scalpel blades in medium, and the cells were seeded in tissue culture dishes. Then, the cells with organ-specific metastasis potential were reinoculated into the armpit of nude mice, respectively. This processes were repeated to establish the organ-specific metastatic sublines of L9981-Luc cell line more than 10 times. Finally, the organ-specific metastasis sublines of L9981-Luc were screened and established, which the four cell lines have the characteristics only metastasized to brian, lung, bone and mediastinal lymph node. Results A group of organ-specific metastasis cell

  13. Establishing an academic laboratory: mentoring as a business model.

    Greco, Valentina

    2014-11-01

    It is a tremendous honor for my group and me to receive the recognition of the 2014 Women in Cell Biology Junior Award. I would like to take the opportunity of this essay to describe my scientific journey, discuss my philosophy about running a group, and propose what I think is a generalizable model to efficiently establish an academic laboratory. This essay is about my view on the critical components that go into establishing a highly functional academic laboratory during the current tough, competitive times. © 2014 Greco.

  14. Establishment of animal model with half-liver cirrhosis

    Yang Zhenghan; Zhou Cheng; Chen Min; Xie Jingxia; Zhang Yuewu; Hu Bifang; Mo Hongbo; Wu Xiao

    2003-01-01

    Objective: To establish a new cirrhosis model suitable for imaging study. Methods: Via a 4 F catheter, 50-100 μl of carbon tetrachloride was injected into the left or right hepatic artery of 12 dogs fortnightly. Liver functional test, imaging study, and pathological examination were performed in these dogs regularly. Results: As the times of injection increased, necrosis of hepatocytes, fibrosis, and cirrhosis of the liver aggravated. In each dog, cirrhosis was more serious in the half liver with carbon tetrachloride injection than in the other half liver without carbon tetrachloride injection. With this model, it was convenient to perform the imaging study of liver cirrhosis. Conclusion: Animal model with half-liver cirrhosis can be established by combining catheter technique and traditional method

  15. A framework to establish credibility of computational models in biology.

    Patterson, Eann A; Whelan, Maurice P

    2017-10-01

    Computational models in biology and biomedical science are often constructed to aid people's understanding of phenomena or to inform decisions with socioeconomic consequences. Model credibility is the willingness of people to trust a model's predictions and is often difficult to establish for computational biology models. A 3 × 3 matrix has been proposed to allow such models to be categorised with respect to their testability and epistemic foundation in order to guide the selection of an appropriate process of validation to supply evidence to establish credibility. Three approaches to validation are identified that can be deployed depending on whether a model is deemed untestable, testable or lies somewhere in between. In the latter two cases, the validation process involves the quantification of uncertainty which is a key output. The issues arising due to the complexity and inherent variability of biological systems are discussed and the creation of 'digital twins' proposed as a means to alleviate the issues and provide a more robust, transparent and traceable route to model credibility and acceptance. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

  16. A strategy to establish Food Safety Model Repositories.

    Plaza-Rodríguez, C; Thoens, C; Falenski, A; Weiser, A A; Appel, B; Kaesbohrer, A; Filter, M

    2015-07-02

    Transferring the knowledge of predictive microbiology into real world food manufacturing applications is still a major challenge for the whole food safety modelling community. To facilitate this process, a strategy for creating open, community driven and web-based predictive microbial model repositories is proposed. These collaborative model resources could significantly improve the transfer of knowledge from research into commercial and governmental applications and also increase efficiency, transparency and usability of predictive models. To demonstrate the feasibility, predictive models of Salmonella in beef previously published in the scientific literature were re-implemented using an open source software tool called PMM-Lab. The models were made publicly available in a Food Safety Model Repository within the OpenML for Predictive Modelling in Food community project. Three different approaches were used to create new models in the model repositories: (1) all information relevant for model re-implementation is available in a scientific publication, (2) model parameters can be imported from tabular parameter collections and (3) models have to be generated from experimental data or primary model parameters. All three approaches were demonstrated in the paper. The sample Food Safety Model Repository is available via: http://sourceforge.net/projects/microbialmodelingexchange/files/models and the PMM-Lab software can be downloaded from http://sourceforge.net/projects/pmmlab/. This work also illustrates that a standardized information exchange format for predictive microbial models, as the key component of this strategy, could be established by adoption of resources from the Systems Biology domain. Copyright © 2015. Published by Elsevier B.V.

  17. Establishing Prostate Cancer Patient Derived Xenografts: Lessons Learned From Older Studies

    Russell, Pamela J; Russell, Peter; Rudduck, Christina; Tse, Brian W-C; Williams, Elizabeth D; Raghavan, Derek

    2015-01-01

    Background Understanding the progression of prostate cancer to androgen-independence/castrate resistance and development of preclinical testing models are important for developing new prostate cancer therapies. This report describes studies performed 30 years ago, which demonstrate utility and shortfalls of xenografting to preclinical modeling. Methods We subcutaneously implanted male nude mice with small prostate cancer fragments from transurethral resection of the prostate (TURP) from 29 pa...

  18. Establishment of animal model of dual liver transplantation in rat.

    Ying Zhang

    Full Text Available The animal model of the whole-size and reduced-size liver transplantation in both rat and mouse has been successfully established. Because of the difficulties and complexities in microsurgical technology, the animal model of dual liver transplantation was still not established for twelve years since the first human dual liver transplantation has been made a success. There is an essential need to establish this animal model to lay a basic foundation for clinical practice. To study the physiological and histopathological changes of dual liver transplantation, "Y" type vein from the cross part between vena cava and two iliac of donor and "Y' type prosthesis were employed to recanalize portal vein and the bile duct between dual liver grafts and recipient. The dual right upper lobes about 45-50% of the recipient liver volume were taken as donor, one was orthotopically implanted at its original position, the other was rotated 180° sagitally and heterotopically positioned in the left upper quadrant. Microcirculation parameters, liver function, immunohistochemistry and survival were analyzed to evaluate the function of dual liver grafts. No significant difference in the hepatic microcirculatory flow was found between two grafts in the first 90 minutes after reperfusion. Light and electronic microscope showed the liver architecture was maintained without obvious features of cellular destruction and the continuity of the endothelium was preserved. Only 3 heterotopically positioned graft appeared patchy desquamation of endothelial cell, mitochondrial swelling and hepatocytes cytoplasmic vacuolization. Immunohistochemistry revealed there is no difference in hepatocyte activity and the ability of endothelia to contract and relax after reperfusion between dual grafts. Dual grafts made a rapid amelioration of liver function after reperfusion. 7 rats survived more than 7 days with survival rate of 58.3.%. Using "Y" type vein and bile duct prosthesis, we

  19. Rabbit models of cerebral vasospasm established with endovascular puncture

    Tu Jianfei; Liu Yizhi; Ji Jiansong; Zhao Zhongwei

    2008-01-01

    Objective: To investigate the method of endovascular puncture to establish rabbit models of cerebral vasospasm. Methods: New Zealand white rabbits were divided into 5 groups (12 h, 1 d, 2 d, 3 d and 7 d) randomly, and each group was separated into subarachnoid hemorrhage (SAH) subgroup (n=5) and control subgroup (n=2). cerebral vascular spasm (CVS) models were established after SAH with endovascular puncture. CT scans before and after operation were performed. The internal diameters and the wall thicknesses of posterior communicans artery (PcoA) and basilar artery (BA) were measured with HE stain after the animals were executed. Results: CVS model was successfully eastblished in 35 rabbits (SAH subgroup 25, control subgroup 10), resulting a successful rate of 48.61%. Compared with control subgroup, PcoA and BA showed shrinkage of internal diameters of 43.60% and 51.82% 12 h after SAH, respectively, and the shrinkage appeared as biphasic patterns until the 7th study day with another peaks of 29.32% and 45.19%, respectively. Conclusions: Endovascular puncture is an effective method to establish rabbit of CVS. The death rate of animals can be decreased with the asage of new interventional material and perfection for the details of operation. (authors)

  20. A new cerebral vasospasm model established with endovascular puncture technique

    Tu Jianfei; Liu Yizhi; Ji Jiansong; Zhao Zhongwei

    2011-01-01

    Objective: To investigate the method of establishing cerebral vasospasm (CVS) models in rabbits by using endovascular puncture technique. Methods: Endovascular puncture procedure was performed in 78 New Zealand white rabbits to produce subarachnoid hemorrhage (SAH). The survival rabbits were randomly divided into seven groups (3 h, 12 h, 1 d, 2 d, 3 d, 7 d and 14 d), with five rabbits in each group for both study group (SAH group) and control group. Cerebral CT scanning was carried out in all rabbits both before and after the operation. The inner diameter and the thickness of vascular wall of both posterior communicating artery (PcoA) and basilar artery (BA) were determined after the animals were sacrificed, and the results were analyzed. Results: Of 78 experimental rabbits, CVS model was successfully established in 45, including 35 of SAH group and 10 control subgroup. The technical success rate was 57.7%. Twelve hours after the procedure, the inner diameter of PcoA and BA in SAH group was decreased by 45.6% and 52.3%, respectively, when compared with these in control group. The vascular narrowing showed biphasic changes, the inner diameter markedly decreased again at the 7th day when the decrease reached its peak to 31.2% and 48.6%, respectively. Conclusion: Endovascular puncture technique is an effective method to establish CVS models in rabbits. The death rate of experimental animals can be decreased if new interventional material is used and the manipulation is carefully performed. (authors)

  1. Models of invasion and establishment of African Mustard (Brassica tournefortii)

    Berry, Kristin H.; Gowan, Timothy A.; Miller, David M.; Brooks, Matthew L.

    2015-01-01

    Introduced exotic plants can drive ecosystem change. We studied invasion and establishment ofBrassica tournefortii (African mustard), a noxious weed, in the Chemehuevi Valley, western Sonoran Desert, California. We used long-term data sets of photographs, transects for biomass of annual plants, and densities of African mustard collected at irregular intervals between 1979 and 2009. We suggest that African mustard may have been present in low numbers along the main route of travel, a highway, in the late 1970s; invaded the valley along a major axial valley ephemeral stream channel and the highway; and by 2009, colonized 22 km into the eastern part of the valley. We developed predictive models for invasibility and establishment of African mustard. Both during the initial invasion and after establishment, significant predictor variables of African mustard densities were surficial geology, proximity to the highway and axial valley ephemeral stream channel, and number of small ephemeral stream channels. The axial valley ephemeral stream channel was the most vulnerable of the variables to invasions. Overall, African mustard rapidly colonized and quickly became established in naturally disturbed areas, such as stream channels, where geological surfaces were young and soils were weakly developed. Older geological surfaces (e.g., desert pavements with soils 140,000 to 300,000 years old) were less vulnerable. Microhabitats also influenced densities of African mustard, with densities higher under shrubs than in the interspaces. As African mustard became established, the proportional biomass of native winter annual plants declined. Early control is important because African mustard can colonize and become well established across a valley in 20 yr.

  2. [Establishment of a comprehensive database for laryngeal cancer related genes and the miRNAs].

    Li, Mengjiao; E, Qimin; Liu, Jialin; Huang, Tingting; Liang, Chuanyu

    2015-09-01

    By collecting and analyzing the laryngeal cancer related genes and the miRNAs, to build a comprehensive laryngeal cancer-related gene database, which differs from the current biological information database with complex and clumsy structure and focuses on the theme of gene and miRNA, and it could make the research and teaching more convenient and efficient. Based on the B/S architecture, using Apache as a Web server, MySQL as coding language of database design and PHP as coding language of web design, a comprehensive database for laryngeal cancer-related genes was established, providing with the gene tables, protein tables, miRNA tables and clinical information tables of the patients with laryngeal cancer. The established database containsed 207 laryngeal cancer related genes, 243 proteins, 26 miRNAs, and their particular information such as mutations, methylations, diversified expressions, and the empirical references of laryngeal cancer relevant molecules. The database could be accessed and operated via the Internet, by which browsing and retrieval of the information were performed. The database were maintained and updated regularly. The database for laryngeal cancer related genes is resource-integrated and user-friendly, providing a genetic information query tool for the study of laryngeal cancer.

  3. Establishing a cat model of acute optic nerve injury

    2007-01-01

    BACKGROUND: In order to investigate the progress in optic nerve injury and the following regeneration and repair, many kinds of animal models of optic nerve injury have been established, such as models of acute and chronic ocular hypertension, compression, amputating wound, ischemia reperfusion or hypoxia,intravitreal injection of excitatory amino acids, etc. However, most of these models are established by squeezing intraorbital optic nerve, and suitable for ophthalmology, and there are fewer models suitable for the acute cranial contusion in neurosurgery.OBJECTIVE: To observe the changes of optic nerve after acute injury, and the characteristics of methods for establishing model of acute optic nerve injury in cats.DESIGN: A complete randomized grouping and controlled animal trial.SETTING: Department of Neurosurgery, General Hospital of Ji'nan Military Area Command of Chinese PLA.MATERIALS: Twenty-eight healthy adult cats, common degree, either sex, weighing 2.0 - 3.5 kg, were provided by the animal experimental center of Fudan University. The cats were randomly divided into control group (n =3) and model group (n =25), and 5 cats in the model group were observed at 6 hours and 1,3, 7 and 14 days after injury respectively. JX-2000 biological signal processing system (Department of Physiology, Second Military Medical University of Chinese PLA, Shanghai); Inverted phase contrast microscope (Olympus); Axioplan 2 imaging microgram analytical system (Labsystems).METHODS: The experiments were carried out in the Department of Neurosurgery, General Hospital of Jinan Military Area Command of Chinese PLA from June 2004 to June 2005. The cats in the model groups were made into models of acute optic nerve injury: The cats were anesthetized, then the limbs were fixed in a lateral recumbent position. Pterion approach in human was imitated, the operative incision was made along the line between lateral canthus and tragus, and it could be seen deep along the skull base that white

  4. Necitumumab in Metastatic Squamous Cell Lung Cancer: Establishing a Value-Based Cost.

    Goldstein, Daniel A; Chen, Qiushi; Ayer, Turgay; Howard, David H; Lipscomb, Joseph; Ramalingam, Suresh S; Khuri, Fadlo R; Flowers, Christopher R

    2015-12-01

    The SQUIRE trial demonstrated that adding necitumumab to chemotherapy for patients with metastatic squamous cell lung cancer (mSqCLC) increased median overall survival by 1.6 months (hazard ratio, 0.84). However, the costs and value associated with this intervention remains unclear. Value-based pricing links the price of a drug to the benefit that it provides and is a novel method to establish prices for new treatments. To evaluate the range of drug costs for which adding necitumumab to chemotherapy could be considered cost-effective. We developed a Markov model using data from multiple sources, including the SQUIRE trial, which compared standard chemotherapy with and without necitumumab as first-line treatment of mSqCLC, to evaluate the costs and patient life expectancies associated with each regimen. In the analysis, patients were modeled to receive gemcitabine and cisplatin for 6 cycles or gemcitabine, cisplatin, and necitumumab for 6 cycles followed by maintenance necitumumab. Our model's clinical inputs were the survival estimates and frequency of adverse events (AEs) described in the SQUIRE trial. Log-logistic models were fitted to the survival distributions in the SQUIRE trial. The cost inputs included drug costs, based on the Medicare average sale prices, and costs for drug administration and management of AEs, based on Medicare reimbursement rates (all in 2014 US dollars). We evaluated incremental cost-effectiveness ratios (ICERs) for the use of necitumumab across a range of values for its cost. Model robustness was assessed by probabilistic sensitivity analyses, based on 10 000 Monte Carlo simulations, sampling values from the distributions of all model parameters. In the base case analysis, the addition of necitumumab to the treatment regimen produced an incremental survival benefit of 0.15 life-years and 0.11 quality-adjusted life-years (QALYs). The probabilistic sensitivity analyses established that when necitumumab cost less than $563 and less than

  5. Establishing a business process reference model for Universities

    Svensson, Carsten; Hvolby, Hans-Henrik

    2012-01-01

    Modern universities are by any standard complex organizations that, from an IT perspective, present a number of unique challenges. This paper will propose establishing a business process reference framework. The benefit to the users would be a better understanding of the system landscape, business......) have gained popularity among organizations in both the private and public sectors. We speculate that this success can be replicated in a university setting. Furthermore the paper will outline how the research group suggests moving ahead with the research which will lead to a reference model....

  6. A reproducible brain tumour model established from human glioblastoma biopsies

    Wang, Jian; Chekenya, Martha; Bjerkvig, Rolf; Enger, Per Ø; Miletic, Hrvoje; Sakariassen, Per Ø; Huszthy, Peter C; Jacobsen, Hege; Brekkå, Narve; Li, Xingang; Zhao, Peng; Mørk, Sverre

    2009-01-01

    Establishing clinically relevant animal models of glioblastoma multiforme (GBM) remains a challenge, and many commonly used cell line-based models do not recapitulate the invasive growth patterns of patient GBMs. Previously, we have reported the formation of highly invasive tumour xenografts in nude rats from human GBMs. However, implementing tumour models based on primary tissue requires that these models can be sufficiently standardised with consistently high take rates. In this work, we collected data on growth kinetics from a material of 29 biopsies xenografted in nude rats, and characterised this model with an emphasis on neuropathological and radiological features. The tumour take rate for xenografted GBM biopsies were 96% and remained close to 100% at subsequent passages in vivo, whereas only one of four lower grade tumours engrafted. Average time from transplantation to the onset of symptoms was 125 days ± 11.5 SEM. Histologically, the primary xenografts recapitulated the invasive features of the parent tumours while endothelial cell proliferations and necrosis were mostly absent. After 4-5 in vivo passages, the tumours became more vascular with necrotic areas, but also appeared more circumscribed. MRI typically revealed changes related to tumour growth, several months prior to the onset of symptoms. In vivo passaging of patient GBM biopsies produced tumours representative of the patient tumours, with high take rates and a reproducible disease course. The model provides combinations of angiogenic and invasive phenotypes and represents a good alternative to in vitro propagated cell lines for dissecting mechanisms of brain tumour progression

  7. Establishment of selected acute pulmonary thromboembolism model in experimental sheep

    Fan Jihai; Gu Xiulian; Chao Shengwu; Zhang Peng; Fan Ruilin; Wang Li'na; Wang Lulu; Wang Ling; Li Bo; Chen Taotao

    2010-01-01

    Objective: To establish a selected acute pulmonary thromboembolism model in experimental sheep suitable for animal experiment. Methods: By using Seldinger's technique the catheter sheath was placed in both the femoral vein and femoral artery in ten sheep. Under C-arm DSA guidance the catheter was inserted through the catheter sheath into the pulmonary artery. Via the catheter appropriate amount of sheep autologous blood clots was injected into the selected pulmonary arteries. The selected acute pulmonary thromboembolism model was thus established. Pulmonary angiography was performed to check the results. The pulmonary arterial pressure, femoral artery pressure,heart rates and partial pressure of oxygen in arterial blood (PaO 2 ) were determined both before and after the treatment. The above parameters obtained after the procedure were compared with the recorded parameters measured before the procedure, and the sheep model quality was evaluated. Results: The baseline of pulmonary arterial pressure was (27.30 ± 9.58) mmHg,femoral artery pressure was (126.4 ± 13.72) mmHg, heart rate was (103 ± 15) bpm and PaO 2 was (87.7 ± 12.04) mmHg. Sixty minutes after the injection of (30 ± 5) ml thrombotic agglomerates, the pulmonary arterial pressures rose to (52 ± 49) mmHg, femoral artery pressures dropped to (100 ± 21) mmHg. The heart rates went up to (150 ± 26) bpm. The PaO 2 fell to (25.3 ± 11.2) mmHg. After the procedure the above parameters were significantly different from that measured before the procedure in all ten animals (P < 0.01). The pulmonary arteriography clearly demonstrated that the selected pulmonary arteries were successfully embolized. Conclusion: The anatomy of sheep's femoral veins,vena cava system, pulmonary artery and right heart system are suitable for the establishment of the catheter passage, for this reason, selected acute pulmonary thromboembolism model can be easily created in experimental sheep. The technique is feasible and the model

  8. Establishing a Business Process Reference Model for Universities

    Svensson, Carsten

    2012-09-01

    Modern universities are by any standard complex organizations that, from an IT perspective, present a number of unique challenges. This paper will propose establishing a business process reference framework. The benefit to the users would be a better understanding of the system landscape, business process enablement, collection of performance data and systematic reuse of existing community experience and knowledge. For these reasons reference models such as the SCOR (Supply Chain Operations Reference), DCOR (Design Chain Operations Reference) and ITIL (Information Technology Infrastructure Library) have gained popularity among organizations in both the private and public sectors. We speculate that this success can be replicated in a university setting. Furthermore the paper will outline how the research group suggests moving ahead with the research which will lead to a reference model.

  9. [Establishment of rat model of psychical erectile dysfunction].

    Wang, Qiu-lin; Wang, Shu-ren; Duan, Jin

    2006-01-01

    To set up a method of establishing the animal model of psychical erectile dysfunction with emotional stress. All thirty-six male rats with normal sexual function were divided into three groups, i. e. normal group, model group and demasculinized group randomly according to their weights. The rats in the model group were suspended upside down in midair over the water and irritated repeatedly. Two weeks later, the sexual abilities of all rats, i. e. the times of mounting and intromitting the estrus female rats, the latent period of mounting, intromission and ejaculation, were recorded, and the number of rats that had sexual activities was also counted. And the hemorheology indices of the rats were measured. Compared with the normal rats, the latency of mounting [(152.5 +/- 24.6) s vs (42.4 +/- 9.6) s] and intromission [(437.0 +/- 67.7) s vs (130.8 +/- 39.1) s] of the model rats were longer (P 0.05). The hemorheology indices, e. g. blood viscosity, hematocrit (Hct) and red cell aggregation (RCA), of the model rats was significant higher than that of the normal and demasculinized rats (P erectile dysfunction can be made ideally with psychical stress.

  10. Establishing a general medical outpatient clinic for cancer survivors in a public city hospital setting.

    Goytia, Elliott J; Lounsbury, David W; McCabe, Mary S; Weiss, Elisa; Newcomer, Meghan; Nelson, Deena J; Brennessel, Debra; Rapkin, Bruce D; Kemeny, M Margaret

    2009-11-01

    Many cancer centers and community hospitals are developing novel models of survivorship care. However, few are specifically focused on services for socio-economically disadvantaged cancer survivors. To describe a new model of survivorship care serving culturally diverse, urban adult cancer patients and to present findings from a feasibility evaluation. Adult cancer patients treated at a public city hospital cancer center. The clinic provides comprehensive medical and psychosocial services for patients within a public hospital cancer center where they receive their oncology care. Longitudinal data collected over a 3-year period were used to describe patient demographics, patient needs, and services delivered. Since inception, 410 cancer patients have been served. Demand for services has grown steadily. Hypertension was the most frequent comorbid condition treated. Pain, depression, cardiovascular disease, hyperlipidemia, and bowel dysfunction were the most common post-treatment problems experienced by the patients. Financial counseling was an important patient resource. This new clinical service has been well-integrated into its public urban hospital setting and constitutes an innovative model of health-care delivery for socio-economically challenged, culturally diverse adult cancer survivors.

  11. A Generalized Dynamic Model of Geared System: Establishment and Application

    Hui Liu

    2011-12-01

    Full Text Available In order to make the dynamic characteristic simulation of the ordinary and planetary gears drive more accurate and more efficient , a generalized dynamic model of geared system is established including internal and external mesh gears in this paper. It is used to build a mathematical model, which achieves the auto judgment of the gear mesh state. We do not need to concern about active or passive gears any more, and the complicated power flow analysis can be avoided. With the numerical integration computation, the axis orbits diagram and dynamic gear mesh force characteristic are acquired and the results show that the dynamic response of translational displacement is greater when contacting line direction change is considered, and with the quickly change of direction of contacting line, the amplitude of mesh force would be increased, which easily causes the damage to the gear tooth. Moreover, compared with ordinary gear, dynamic responses of planetary gear would be affected greater by the gear backlash. Simulation results show the effectiveness of the generalized dynamic model and the mathematical model.

  12. Examining lung cancer risks across different industries and occupations in Ontario, Canada: the establishment of the Occupational Disease Surveillance System.

    Jung, James K H; Feinstein, Saul G; Palma Lazgare, Luis; Macleod, Jill S; Arrandale, Victoria H; McLeod, Christopher B; Peter, Alice; Demers, Paul A

    2018-05-07

    The Occupational Disease Surveillance System (ODSS) was established in Ontario, Canada by linking a cohort of workers with data created from Workplace Safety and Insurance Board (WSIB) claims to administrative health databases. The aim of this study was to use ODSS to identify high-risk industry and occupation groups for lung cancer in Ontario. Workers in the WSIB lost time claims database were linked to the Ontario Cancer Registry using subjects' health insurance numbers, name, sex, birthdate and death date (if applicable). Several occupations and industries known to be at increased risk were outlined a priori to examine whether ODSS could replicate these associations. Age-adjusted, sex-stratified Cox proportional hazard models compared the risk of lung cancer within one industry/occupation versus all other groups in the cohort. Workers with a lung cancer diagnosis prior to cohort entry were excluded for analysis, leaving 2 187 762 workers for analysis. During the 1983 to 2014 follow-up, 34 661 workers in the cohort were diagnosed with lung cancer. Among expected high-risk industries, elevated risks were observed among workers in quarries/sand pits and construction industries for both sexes, and among males in metal mines, iron foundries, non-metallic mineral products industries and transportation industries. Excess risk was also observed among occupations in drilling/blasting, other mining/quarrying, mineral ore treating, excavating/grading/paving, truck driving, painting, bus driving and construction. This current surveillance system identified several established high-risk groups for lung cancer and could be used for ongoing surveillance of occupational lung cancer in Ontario. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  13. A reproducible brain tumour model established from human glioblastoma biopsies

    Li Xingang

    2009-12-01

    Full Text Available Abstract Background Establishing clinically relevant animal models of glioblastoma multiforme (GBM remains a challenge, and many commonly used cell line-based models do not recapitulate the invasive growth patterns of patient GBMs. Previously, we have reported the formation of highly invasive tumour xenografts in nude rats from human GBMs. However, implementing tumour models based on primary tissue requires that these models can be sufficiently standardised with consistently high take rates. Methods In this work, we collected data on growth kinetics from a material of 29 biopsies xenografted in nude rats, and characterised this model with an emphasis on neuropathological and radiological features. Results The tumour take rate for xenografted GBM biopsies were 96% and remained close to 100% at subsequent passages in vivo, whereas only one of four lower grade tumours engrafted. Average time from transplantation to the onset of symptoms was 125 days ± 11.5 SEM. Histologically, the primary xenografts recapitulated the invasive features of the parent tumours while endothelial cell proliferations and necrosis were mostly absent. After 4-5 in vivo passages, the tumours became more vascular with necrotic areas, but also appeared more circumscribed. MRI typically revealed changes related to tumour growth, several months prior to the onset of symptoms. Conclusions In vivo passaging of patient GBM biopsies produced tumours representative of the patient tumours, with high take rates and a reproducible disease course. The model provides combinations of angiogenic and invasive phenotypes and represents a good alternative to in vitro propagated cell lines for dissecting mechanisms of brain tumour progression.

  14. Establishing psychiatric registrars' competence in psychotherapy: a portfolio based model.

    Naidu, T; Ramlall, S

    2008-11-01

    During most of the latter part of the last century, South Africa has followed international trends in the training of psychiatrists. Training programmes have become increasingly focused on the neurobiological aspects of psychiatric disorders with less attention being paid to psychotherapy. This is consistent with developments in psychiatric research. In the clinical arena this manifests as a focus on pharmacological and medically based interventions and a resulting relative inattention to non-pharmacological interventions, most especially psychotherapy. In an effort to address this imbalance there has been an international initiative, over the past two decades, to establish an acceptable level of competence in psychotherapy in the training of psychiatrists. A South African programme is needed that can take account of international trends and adapt them for the local context. In order to produce a programme for establishing competence in psychotherapy for psychiatric registrars at the Nelson R. Mandela School of Medicine, the authors examine directives for the development of psychotherapy skills from international regulatory bodies for graduate medical training and their application. Defining and setting preliminary standards for competence is emphasized. A programme based on five core psychotherapy components using a portfolio based model to facilitate learning and assessment of competence in psychotherapy, is proposed.

  15. The use of bone scintigraphy to establish cancer extension records: application to prostate and breast cancers

    Methlin, G.; Grob, J.C.; Moyses, B.; Deschler, J.M.; Ott, G.; Berthelen, B.

    1975-01-01

    The recent development of the technique described, especially in the systematic search for metastases was due to the introduction of stannous diphosphate complexed with sup(99m)Tc well suited to bone scintigraphy. The documents are obtained in two stages. First a whole-body scintigraph is taken by means of an omniview device fitted to a Picker dynacamera, and this scanning phase is followed immediately by static views centred mainly on abnormal or doubtful regions. The results are given for 136 breast cancers and 61 prostate cancers, two cancers particularly liable to affect the bone, and show that scintigraphy offers positive advantages over radiological investigations. These advantages are offset to some extent by the non-specific nature of the hyperfixing regions since different diseases involving changes in the bone structure can give similar images, but for breast and prostate cancers bone scintigraphy presents distinct possibilities in the search for metastases of the skeleton [fr

  16. [Establishment of mouse endometrial injury model by electrocoagulation].

    Hu, Xiaoxiao; Lin, Xiaona; Jiang, Yinshen; Shi, Libing; Wang, Jieyu; Zhao, Lijuan; Zhang, Songying

    2014-12-23

    To establish the murine model of moderate endometrial injury. Electrocoagulation was applied to induce endometrial injury of ICR mice with 0.5 watts power while contralateral uterine cavity acted as control without electrocoagulation. The endometrial histomorphology was observed in 7 days later by microscopy and fetal number of each lateral uterus assessed at 17.5 days after pregnancy. At 7 days post-electrocoagulation, the average endometrial thickness of operating side was significantly thinner than that of control side (1.14 ± 0.08 vs 1.88 ± 0.15 mm, P electrocoagulation injury shows morphologic changes and decreased fertile ability. It has potential uses for animal studies of endometrial injury treatment.

  17. The establishment of animal model of acute massive pulmonary embolism

    Lu Junliang; Yang Ning; Yang Jianping; Ma Junshan; Zhao Shijun

    2008-01-01

    Objective: To find a way of establishing the model of acute massive pulmonary embolism in dog. Methods: Seven dogs were selected with self-clots made outside the body transferring through a 10 F guiding catheter into the central branch of pulmonary artery via the femoral vein approach on one side and then under pressure monitor of pulmonary artery until the very branch of pulmonary artery was occluded. Blood gas and pulmonary arterial pressure were tested before and after the embolization, Pulmonary artery pressure was continuously monitored together with the examinations of angiography. The bilateral lung specimens were resected for histological examination 12 hours in average after the embolization for comparative study. Results: One animal died of cardiogenic shock after clots injection; the other one presented with tachycardia and premature ventricular beat causing partial recanalization 12 h later. The others were occluded successfully in central branch of pulmonary artery and the pulmonary arterial pressure reached above 50 mmHg after occlusion. Pathologic examination showed the formation of red and mix thrombi within the vascular lumens. Conclusions: This method for making acute massive pulmonary embolism animal model was reliable, feasible and reproducible, and could provide an animal model of acute massive pulmonary embolism for other correlative experiments. (authors)

  18. Mathematical modeling of cancer metabolism.

    Medina, Miguel Ángel

    2018-04-01

    Systemic approaches are needed and useful for the study of the very complex issue of cancer. Modeling has a central position in these systemic approaches. Metabolic reprogramming is nowadays acknowledged as an essential hallmark of cancer. Mathematical modeling could contribute to a better understanding of cancer metabolic reprogramming and to identify new potential ways of therapeutic intervention. Herein, I review several alternative approaches to metabolic modeling and their current and future impact in oncology. Copyright © 2018 Elsevier B.V. All rights reserved.

  19. Prostate Cancer Risk Prediction Models

    Developing statistical models that estimate the probability of developing prostate cancer over a defined period of time will help clinicians identify individuals at higher risk of specific cancers, allowing for earlier or more frequent screening and counseling of behavioral changes to decrease risk.

  20. Colorectal Cancer Risk Prediction Models

    Developing statistical models that estimate the probability of developing colorectal cancer over a defined period of time will help clinicians identify individuals at higher risk of specific cancers, allowing for earlier or more frequent screening and counseling of behavioral changes to decrease risk.

  1. Esophageal Cancer Risk Prediction Models

    Developing statistical models that estimate the probability of developing esophageal cancer over a defined period of time will help clinicians identify individuals at higher risk of specific cancers, allowing for earlier or more frequent screening and counseling of behavioral changes to decrease risk.

  2. Bladder Cancer Risk Prediction Models

    Developing statistical models that estimate the probability of developing bladder cancer over a defined period of time will help clinicians identify individuals at higher risk of specific cancers, allowing for earlier or more frequent screening and counseling of behavioral changes to decrease risk.

  3. Lung Cancer Risk Prediction Models

    Developing statistical models that estimate the probability of developing lung cancer over a defined period of time will help clinicians identify individuals at higher risk of specific cancers, allowing for earlier or more frequent screening and counseling of behavioral changes to decrease risk.

  4. Breast Cancer Risk Prediction Models

    Developing statistical models that estimate the probability of developing breast cancer over a defined period of time will help clinicians identify individuals at higher risk of specific cancers, allowing for earlier or more frequent screening and counseling of behavioral changes to decrease risk.

  5. Pancreatic Cancer Risk Prediction Models

    Developing statistical models that estimate the probability of developing pancreatic cancer over a defined period of time will help clinicians identify individuals at higher risk of specific cancers, allowing for earlier or more frequent screening and counseling of behavioral changes to decrease risk.

  6. Ovarian Cancer Risk Prediction Models

    Developing statistical models that estimate the probability of developing ovarian cancer over a defined period of time will help clinicians identify individuals at higher risk of specific cancers, allowing for earlier or more frequent screening and counseling of behavioral changes to decrease risk.

  7. Liver Cancer Risk Prediction Models

    Developing statistical models that estimate the probability of developing liver cancer over a defined period of time will help clinicians identify individuals at higher risk of specific cancers, allowing for earlier or more frequent screening and counseling of behavioral changes to decrease risk.

  8. Testicular Cancer Risk Prediction Models

    Developing statistical models that estimate the probability of testicular cervical cancer over a defined period of time will help clinicians identify individuals at higher risk of specific cancers, allowing for earlier or more frequent screening and counseling of behavioral changes to decrease risk.

  9. Cervical Cancer Risk Prediction Models

    Developing statistical models that estimate the probability of developing cervical cancer over a defined period of time will help clinicians identify individuals at higher risk of specific cancers, allowing for earlier or more frequent screening and counseling of behavioral changes to decrease risk.

  10. Establishment of reproducible osteosarcoma rat model using orthotopic implantation technique.

    Yu, Zhe; Sun, Honghui; Fan, Qingyu; Long, Hua; Yang, Tongtao; Ma, Bao'an

    2009-05-01

    In experimental musculoskeletal oncology, there remains a need for animal models that can be used to assess the efficacy of new and innovative treatment methodologies for bone tumors. Rat plays a very important role in the bone field especially in the evaluation of metabolic bone diseases. The objective of this study was to develop a rat osteosarcoma model for evaluation of new surgical and molecular methods of treatment for extremity sarcoma. One hundred male SD rats weighing 125.45+/-8.19 g were divided into 5 groups and anesthetized intraperitoneally with 10% chloral hydrate. Orthotopic implantation models of rat osteosarcoma were performed by injecting directly into the SD rat femur with a needle for inoculation with SD tumor cells. In the first step of the experiment, 2x10(5) to 1x10(6) UMR106 cells in 50 microl were injected intraosseously into median or distal part of the femoral shaft and the tumor take rate was determined. The second stage consisted of determining tumor volume, correlating findings from ultrasound with findings from necropsia and determining time of survival. In the third stage, the orthotopically implanted tumors and lung nodules were resected entirely, sectioned, and then counter stained with hematoxylin and eosin for histopathologic evaluation. The tumor take rate was 100% for implants with 8x10(5) tumor cells or more, which was much less than the amount required for subcutaneous implantation, with a high lung metastasis rate of 93.0%. Ultrasound and necropsia findings matched closely (r=0.942; p<0.01), which demonstrated that Doppler ultrasonography is a convenient and reliable technique for measuring cancer at any stage. Tumor growth curve showed that orthotopically implanted tumors expanded vigorously with time-lapse, especially in the first 3 weeks. The median time of survival was 38 days and surgical mortality was 0%. The UMR106 cell line has strong carcinogenic capability and high lung metastasis frequency. The present rat

  11. Consumer attitudes towards the establishment of a national Australian familial cancer research database by the Inherited Cancer Connect (ICCon) Partnership.

    Forrest, Laura; Mitchell, Gillian; Thrupp, Letitia; Petelin, Lara; Richardson, Kate; Mascarenhas, Lyon; Young, Mary-Anne

    2018-01-01

    Clinical genetics units hold large amounts of information which could be utilised to benefit patients and their families. In Australia, a national research database, the Inherited Cancer Connect (ICCon) database, is being established that comprises clinical genetic data held for all carriers of mutations in cancer predisposition genes. Consumer input was sought to establish the acceptability of the inclusion of clinical genetic data into a research database. A qualitative approach using a modified nominal group technique was used to collect data through consumer forums conducted in three Australian states. Individuals who had previously received care from Familial Cancer Centres were invited to participate. Twenty-four consumers participated in three forums. Participants expressed positive attitudes about the establishment of the ICCon database, which were informed by the perceived benefits of the database including improved health outcomes for individuals with inherited cancer syndromes. Most participants were comfortable to waive consent for their clinical information to be included in the research database in a de-identified format. As major stakeholders, consumers have an integral role in contributing to the development and conduct of the ICCon database. As an initial step in the development of the ICCon database, the forums demonstrated consumers' acceptance of important aspects of the database including waiver of consent.

  12. Establishing endangered species recovery criteria using predictive simulation modeling

    McGowan, Conor P.; Catlin, Daniel H.; Shaffer, Terry L.; Gratto-Trevor, Cheri L.; Aron, Carol

    2014-01-01

    Listing a species under the Endangered Species Act (ESA) and developing a recovery plan requires U.S. Fish and Wildlife Service to establish specific and measurable criteria for delisting. Generally, species are listed because they face (or are perceived to face) elevated risk of extinction due to issues such as habitat loss, invasive species, or other factors. Recovery plans identify recovery criteria that reduce extinction risk to an acceptable level. It logically follows that the recovery criteria, the defined conditions for removing a species from ESA protections, need to be closely related to extinction risk. Extinction probability is a population parameter estimated with a model that uses current demographic information to project the population into the future over a number of replicates, calculating the proportion of replicated populations that go extinct. We simulated extinction probabilities of piping plovers in the Great Plains and estimated the relationship between extinction probability and various demographic parameters. We tested the fit of regression models linking initial abundance, productivity, or population growth rate to extinction risk, and then, using the regression parameter estimates, determined the conditions required to reduce extinction probability to some pre-defined acceptable threshold. Binomial regression models with mean population growth rate and the natural log of initial abundance were the best predictors of extinction probability 50 years into the future. For example, based on our regression models, an initial abundance of approximately 2400 females with an expected mean population growth rate of 1.0 will limit extinction risk for piping plovers in the Great Plains to less than 0.048. Our method provides a straightforward way of developing specific and measurable recovery criteria linked directly to the core issue of extinction risk. Published by Elsevier Ltd.

  13. Establishment of an induced rat model of malignant pleural mesothelioma

    Han Dan; Wu Beihai; Yang Hongsheng; Song Guangyi

    2004-01-01

    Objective: To establish a convenient and practical malignant pleural mesothelioma (MPM) model induced by crocidolite in Da Yao, which has a high induction rate and can be used for imaging and multiple experimental studies and is similar to human MPM. Methods 40 mg of crocidolite suspension was injected into the right chest cavity in 100 Wistar rats in the test group, while same amount of sterilized saline water was injected in 20 rats in the control group. The animals were observed daily , and weighted once a month. CT scanning was performed regularly. When the rats were dead or dying, they were dissected immediately and pathological changes were recorded after CT examination. The experiment lasted for 2 years. Results: The overall induction rate was 71.6%. The survival time of the first MPM rat was 285 days. The mean living span of rats with MPM was (469 ± 21) days. The pathological features of the induced MPMs were multiple morphologically and there were some CT features in different periods. CT imaging could show some MPM features and find the tumour earlier. Conclusion: The cause, positions, tissues and clinical condition of induced tumors were the same as humans. The model had a higher similarity with human MPM in differentiation degree and histological type, and the model can be used to study the mechanism of MPM, to discuss the measures of prevention, and to guide clinical diagnosis and treatment. Multi-morphology of the history from the induced tumors could make up the shortage, which was the difficulty in getting all periods of tissue samples in clinical research and being used in imaging and many kinds of researches. It was a valuable animal model to study MPM. (authors)

  14. Adoptively transferred immune T cells eradicate established tumors in spite of cancer-induced immune suppression

    Arina, Ainhoa; Schreiber, Karin; Binder, David C.; Karrison, Theodore; Liu, Rebecca B.; Schreiber, Hans

    2014-01-01

    Myeloid-derived CD11b+Gr1+ suppressor cells (MDSC) and tumor-associated macrophages (TAM) are considered a major obstacle for effective adoptive T cell therapy. Myeloid cells suppress naive T cell proliferation ex vivo and can prevent the generation of T cell responses in vivo. We find, however, that immune T cells adoptively transferred eradicate well-established tumors in the presence of MDSC and TAM which are strongly immunosuppressive ex vivo. These MDSC and TAM were comparable in levels and immunosuppression among different tumor models. Longitudinal microscopy of tumors in vivo revealed that after T cell transfer tumor vasculature and cancer cells disappeared simultaneously. During T-cell mediated tumor destruction, the tumor stroma contained abundant myeloid cells (mainly TAM) that retained their suppressive properties. Preimmunized but not naive mice resisted immune suppression caused by an unrelated tumor-burden supporting the idea that in vivo, myeloid immunosuppressive cells can suppress naive but not memory T cell responses. PMID:24367029

  15. Study on specificity of colon carcinoma-associated serum markers and establishment of SVM prediction model

    Lu Li

    2017-03-01

    Full Text Available We aimed to evaluate the specificity of 12 tumor markers related to colon carcinoma and identify the most sensitive index. Logistic regression and Bhattacharyya distance were used to evaluate the index. Then, different index combinations were used to establish a support vector machine (SVM diagnosis model of malignant colon carcinoma. The accuracy of the model was checked. High accuracy was assumed to indicate the high specificity of the index. Through Logistic regression, three indexes, CEA, HSP60 and CA199, were screened out. Using Bhattacharyya distance, four indexes with the largest Bhattacharyya distance were screened out, including CEA, NSE, AFP, and CA724. The specificity of the combination of the above six indexes was higher than that of other combinations, so did the accuracy of the established SVM identification model. Using Logistic regression and Bhattacharyya distance for detection and establishing an SVM model based on different serum marker combinations can increase diagnostic accuracy, providing a theoretical basis for application of mathematical models in cancer diagnosis.

  16. Patients with established cancer cachexia lack the motivation and self-efficacy to undertake regular structured exercise.

    Wasley, David; Gale, Nichola; Roberts, Sioned; Backx, Karianne; Nelson, Annmarie; van Deursen, Robert; Byrne, Anthony

    2018-02-01

    Patients with advanced cancer frequently suffer a decline in activities associated with involuntary loss of weight and muscle mass (cachexia). This can profoundly affect function and quality of life. Although exercise participation can maintain physical and psychological function in patients with cancer, uptake is low in cachectic patients who are underrepresented in exercise studies. To understand how such patients' experiences are associated with exercise participation, we investigated exercise history, self-confidence, and exercise motivations in patients with established cancer cachexia, and relationships between relevant variables. Lung and gastrointestinal cancer outpatients with established cancer cachexia (n = 196) completed a questionnaire exploring exercise history and key constructs of the Theory of Planned Behaviour relating to perceived control, psychological adjustment, and motivational attitudes. Patients reported low physical activity levels, and few undertook regular structured exercise. Exercise self-efficacy was very low with concerns it could worsen symptoms and cause harm. Patients showed poor perceived control and a strong need for approval but received little advice from health care professionals. Preferences were for low intensity activities, on their own, in the home setting. Regression analysis revealed no significant factors related to the independent variables. Frequently employed higher intensity, group exercise models do not address the motivational and behavioural concerns of cachectic cancer patients in this study. Developing exercise interventions which match perceived abilities and skills is required to address challenges of self-efficacy and perceived control identified. Greater engagement of health professionals with this group is required to explore potential benefits of exercise. Copyright © 2017 John Wiley & Sons, Ltd.

  17. The imagine of establishing China nuclear insurance model

    Wu Yimin

    2010-01-01

    Nuclear power Insurance is one important technique for risk managements of Nuclear power Enterprises. At present, nuclear risk of Nuclear power plants in China has been mainly supported by China Nuclear Insurance pool (hereinafter called CNP) to get coverage from International Nuclear Insurance pool (hereinafter called NIP). CNIP has several advantages to confirm low-cost. Operation, such as large underwriting capacity, international approval and cession, direct writing without agents. However, there are both deficiencies, first, can not get rid of dependence on International markets ; second, in the absence of competition in Self- insurance organizations , tough and opaque premium offer greatly restricted the enthusiasm for Nuclear power plants insuring .But the next ten year is a golden decade for China Nuclear industry development; Nuclear power market is demonstrating tremendous growth potential. With new units put into operation, all kinds of nuclear insurance demand will release when subject-matter insured substantially increase. So, breaking the current bottleneck of China Nuclear Insurance and establishing China Nuclear Insurance (hereinafter called: Nuclear insurance) model adapting to China national conditions will play an important role in Nuclear power development. I made the advice that both domestic nuclear enterprises and general insurance companies initiate a 'Nuclear insurance company'. (authors)

  18. Establishing a model of supratentorial hemorrhage in the piglet

    Shi Yuanhong; Li Zaiwang; Zhang Suming; Xie Minjie; Meng Xiangwu; Xu Jinzhi; Liu Na; Tang Zhouping

    2010-01-01

    The most common site of hemorrhage is the basal ganglia, which exhibits the obvious neurological deficits. In the present study, we aimed to develop a model of supratentorial intracerebral hemorrhage (ICH) with neurological deficits in piglets (6.0 to 8.8 kg). A pediatric urinary catheter with two passages and one balloon was introduced through a burr hole into the right striatum. All the animals received balloon inflation, which was performed by injecting 2.5 ml saline into the balloon through one passage. Then each piglet in experimental group (n=18) received an injection of 1.0-ml autologous arterial blood through the other passage over 2 min and maintained for 5 min. Then, additional 1.5-ml blood was injected over 15 min. Piglets in control group (n=6) received only balloon inflation without blood injection. CT scanning was performed immediately after surgery. A deep hematoma was successfully induced in 16 out of 18 piglets and the hematoma volume was 1.74±0.22 ml (n=5) at 24 hours after surgery. All the piglets with hematoma had behavioral deficits (lame or could not walk) at 24 hours. Tissue damages, such as cell swelling, necrosis and demyelination, appeared at 24 hours in the brain tissues, adjacent to the hematoma, and was aggravated at 48 hours and ameliorated at 7 days after hematoma induction. In conclusion, we have established a simple model of supratentorial ICH in piglets with marked neurological deficits, which is suitable for study of the pathophysiology and treatment of ICH. (author)

  19. Establishing an in vivo model of canine prostate carcinoma using the new cell line CT1258

    Fork, Melani AM; Bullerdiek, Jörn; Nolte, Ingo; Escobar, Hugo Murua; Soller, Jan T; Sterenczak, Katharina A; Willenbrock, Saskia; Winkler, Susanne; Dorsch, Martina; Reimann-Berg, Nicola; Hedrich, Hans J

    2008-01-01

    Prostate cancer is a frequent finding in man. In dogs, malignant disease of the prostate is also of clinical relevance, although it is a less common diagnosis. Even though there are numerous differences in origin and development of the disease, man and dog share many similarities in the pathological presentation. For this reason, the dog might be a useful animal model for prostate malignancies in man. Although prostate cancer is of great importance in veterinary medicine as well as in comparative medicine, there are only few cell lines available. Thus, it was the aim of the present study to determine whether the formerly established prostate carcinoma cell line CT1258 is a suitable tool for in vivo testing, and to distinguish the growth pattern of the induced tumours. For characterisation of the in vivo behaviour of the in vitro established canine prostate carcinoma cell line CT1258, cells were inoculated in 19 NOD.CB17-Prkdc Scid /J (in the following: NOD-Scid) mice, either subcutaneously or intraperitoneally. After sacrifice, the obtained specimens were examined histologically and compared to the pattern of the original tumour in the donor. Cytogenetic investigation was performed. The cell line CT 1258 not only showed to be highly tumourigenic after subcutaneous as well as intraperitoneal inoculation, but also mimicked the behaviour of the original tumour. Tumours induced by inoculation of the cell line CT1258 resemble the situation in naturally occurring prostate carcinoma in the dog, and thus could be used as in vivo model for future studies

  20. Association between Residential Proximity to PERC Dry Cleaning Establishments and Kidney Cancer in New York City

    Jing Ma

    2009-01-01

    Full Text Available Perchloroethylene (PERC is commonly used as a dry cleaning solvent and is believed to be a human carcinogen, with occupational exposure resulting in elevated rates of kidney cancer. Living near a dry cleaning facility using PERC has been demonstrated to increase the risk of PERC exposure throughout the building where the dry cleaning is conducted, and in nearby buildings. We designed this study to test the hypothesis that living in an area where there are many PERC dry cleaners increases PERC exposure and the risk of kidney cancer. We matched the diagnosis of kidney cancer from hospitalization discharge data in New York City for the years 1994–2004 by zip code of patient residence to the zip code density of dry cleaners using PERC, as a surrogate for residential exposure. We controlled for age, race, gender, and median household income. We found a significant association between the density of PERC dry cleaning establishments and the rate of hospital discharges that include a diagnosis of kidney cancer among persons 45 years of age and older living in New York City. The rate ratio increased by 10 to 27% for the populations in zip codes with higher density of PERC dry cleaners. Because our exposure assessment is inexact, we are likely underestimating the real association between exposure to PERC and rates of kidney cancer. Our results support the hypothesis that living near a dry cleaning facility using PERC increases the risk of PERC exposure and of developing kidney cancer. To our knowledge, this study is the first to demonstrate an association between residential PERC exposure and cancer risk.

  1. Association between Residential Proximity to PERC Dry Cleaning Establishments and Kidney Cancer in New York City

    Ma, J.; Lessner, L.; Lessner, L.; Carpenter, D.O.; Schreiber, J.

    2010-01-01

    Perchloroethylene (PERC) is commonly used as a dry cleaning solvent and is believed to be a human carcinogen, with occupational exposure resulting in elevated rates of kidney cancer. Living near a dry cleaning facility using PERC has been demonstrated to increase the risk of PERC exposure throughout the building where the dry cleaning is conducted, and in nearby buildings. We designed this study to test the hypothesis that living in an area where there are many PERC dry cleaners increases PERC exposure and the risk of kidney cancer. We matched the diagnosis of kidney cancer from hospitalization discharge data in New York City for the years 1994-2004 by zip code of patient residence to the zip code density of dry cleaners using PERC, as a surrogate for residential exposure. We controlled for age, race, gender, and median household income. We found a significant association between the density of PERC dry cleaning establishments and the rate of hospital discharges that include a diagnosis of kidney cancer among persons 45 years of age and older living in New York City. The rate ratio increased by 10 to 27% for the populations in zip codes with higher density of PERC dry cleaners. Because our exposure assessment is inexact, we are likely underestimating the real association between exposure to PERC and rates of kidney cancer. Our results support the hypothesis that living near a dry cleaning facility using PERC increases the risk of PERC exposure and of developing kidney cancer. To our knowledge, this study is the first to demonstrate an association between residential PERC exposure and cancer risk.

  2. Animal models for cancer and uses thereof

    Demaria, Marco; Campisi, Judith; van Deursen, Jan M.; Kirkland, James; Tchkonia, Tamara T.; Baker, Darren J.

    2017-01-01

    Non-human animal cancer models are provided herein for identifying and characterizing agents useful for therapy and prophylaxis of cancers, including agents useful for diminishing side effects related to cancer therapies and reducing metastatic disease.

  3. Establishing a Program for Individuals at High Risk for Breast Cancer

    Cadiz, Fernando; Kuerer, Henry M.; Puga, Julio; Camacho, Jamile; Cunill, Eduardo; Arun, Banu

    2013-01-01

    Our need to create a program for individuals at high risk for breast cancer development led us to research the available data on such programs. In this paper, we summarize our findings and our thinking process as we developed our own program. Breast cancer incidence is increasing worldwide. Even though there are known risk factors for breast cancer development, approximately 60% of patients with breast cancer have no known risk factor, although this situation will probably change with further research, especially in genetics. For patients with risk factors based on personal or family history, different models are available for assessing and quantifying risk. Assignment of risk levels permits tailored screening and risk reduction strategies. Potential benefits of specialized programs for women with high breast cancer risk include more cost -effective interventions as a result of patient stratification on the basis of risk; generation of valuable data to advance science; and differentiation of breast programs from other breast cancer units, which can result in increased revenue that can be directed to further improvements in patient care. Guidelines for care of patients at high risk for breast cancer are available from various groups. However, running a high-risk breast program involves much more than applying a guideline. Each high-risk program needs to be designed by its institution with consideration of local resources and country legislation, especially related to genetic issues. Development of a successful high-risk program includes identifying strengths, weaknesses, opportunities, and threats; developing a promotion plan; choosing a risk assessment tool; defining “high risk”; and planning screening and risk reduction strategies for the specific population served by the program. The information in this article may be useful for other institutions considering creation of programs for patients with high breast cancer risk. PMID:23833688

  4. Ancient genes establish stress-induced mutation as a hallmark of cancer.

    Cisneros, Luis; Bussey, Kimberly J; Orr, Adam J; Miočević, Milica; Lineweaver, Charles H; Davies, Paul

    2017-01-01

    Cancer is sometimes depicted as a reversion to single cell behavior in cells adapted to live in a multicellular assembly. If this is the case, one would expect that mutation in cancer disrupts functional mechanisms that suppress cell-level traits detrimental to multicellularity. Such mechanisms should have evolved with or after the emergence of multicellularity. This leads to two related, but distinct hypotheses: 1) Somatic mutations in cancer will occur in genes that are younger than the emergence of multicellularity (1000 million years [MY]); and 2) genes that are frequently mutated in cancer and whose mutations are functionally important for the emergence of the cancer phenotype evolved within the past 1000 million years, and thus would exhibit an age distribution that is skewed to younger genes. In order to investigate these hypotheses we estimated the evolutionary ages of all human genes and then studied the probability of mutation and their biological function in relation to their age and genomic location for both normal germline and cancer contexts. We observed that under a model of uniform random mutation across the genome, controlled for gene size, genes less than 500 MY were more frequently mutated in both cases. Paradoxically, causal genes, defined in the COSMIC Cancer Gene Census, were depleted in this age group. When we used functional enrichment analysis to explain this unexpected result we discovered that COSMIC genes with recessive disease phenotypes were enriched for DNA repair and cell cycle control. The non-mutated genes in these pathways are orthologous to those underlying stress-induced mutation in bacteria, which results in the clustering of single nucleotide variations. COSMIC genes were less common in regions where the probability of observing mutational clusters is high, although they are approximately 2-fold more likely to harbor mutational clusters compared to other human genes. Our results suggest this ancient mutational response to

  5. [Establishing Individualized Medicine for Intractable Cancer Based on Clinical Molecular Pathogenesis].

    Jono, Hirofumi

    2018-01-01

     Although cancer treatment has dramatically improved with the development of molecular-targeted agents over the past decade, identifying eligible patients and predicting the therapeutic effects remain a major challenge. Because intratumoral heterogeneity represents genetic and molecular differences affecting patients' responses to these therapeutic agents, establishing individualized medicine based on precise molecular pathological analysis of tumors is urgently required. This review focuses on the pathogenesis of oral squamous cell carcinoma (OSCC), a common head and neck neoplasm, and introduces our approaches toward developing novel anticancer therapies particularly based on clinical molecular pathogenesis. Deeper understanding of more precise molecular pathogenesis in clinical settings may open up novel strategies for establishing individualized medicine for OSCC.

  6. Disrupting established tumor blood vessels: an emerging therapeutic strategy for cancer.

    McKeage, Mark J; Baguley, Bruce C

    2010-04-15

    The unique characteristics of tumor vasculature represent an attractive target that may be exploited by vascular-targeting anticancer agents. A promising strategy involves the selective disruption of established tumor blood vessels by tumor-vascular disrupting agents (tumor-VDAs), which exhibit antivascular activity, resulting in inhibition of tumor blood flow and extensive necrosis within the tumor core. The tumor-VDA class can be subdivided into flavonoid compounds, which are related to flavone acetic acid, and tubulin-binding compounds. ASA404, of the flavonoid class, is the most advanced tumor-VDA in clinical development and has been evaluated preclinically and in several phase 1 and phase 2 studies. Preclinical studies have demonstrated the selective apoptosis of tumor endothelial cells and the inhibition of tumor blood flow. Synergistic activity was observed with ASA404 and with several chemotherapeutic agents, particularly taxanes. In clinical trials, compared with chemotherapy alone, ASA404 was tolerated well and produced improved activity in patients with nonsmall cell lung cancer when combined with paclitaxel and carboplatin. Phase 3 clinical trials are ongoing. Selectively targeting established tumor vasculature with tumor-VDAs represents a promising and innovative approach to improving the efficacy of standard anticancer therapies. (c) 2010 American Cancer Society.

  7. Sexual Recovery Following Prostate Cancer: Recommendations From 2 Established Canadian Sexual Rehabilitation Clinics.

    Elliott, Stacy; Matthew, Andrew

    2018-04-01

    Supportive sexual health care is much-needed adjuvant care to oncologic management for men with prostate cancer (PCa). To inspire the initiation of biopsychosocial sexual health programming where it does not exist and to inform program enhancement in existing sexual rehabilitation clinics (SRCs). This article reviews the combined 30-year experience of 2 well-established Canadian SRCs for men and their partners after PCa treatments, interwoven with empirical evidence. To comprehensively review the biopsychosocial approach to sexual health assessment of men with PCa and their partners to direct the practicalities of running a successful and sustainable SRC. A full description of the biomedical and psychosocial approaches, inclusive of comprehensive sexual function, the penile rehabilitation controversy, and other medical and relationship issues affecting sexual adjustment, is provided to highlight the relevance of proper assessment and follow-through for sexual adaptation and adjustment. 10 recommendations for a successful SRC are discussed, including the principles behind developing a sustainable business plan, staff acquisition and training, budget, integration of treatment and research priorities, respectful and multidisciplinary approaches to care, and suggestions of visit formats, protocols, and questionnaires. We recommend a phased approach of an SRC into usual care with the option to provide accessible and equitable care to patients not within proximal access of treating institutions. Sexual rehabilitation after treatment for PCa requires a complex treatment process. Providing sustainable sexual rehabilitation programming under the financially strained environment of the Canadian medical system is a challenge; therefore, to provide Canadian patients and their partners with comprehensive cancer care, they deserve a biopsychosocial approach combined with a creative and systematic implementation strategy. Elliott S, Matthew A. Sexual Recovery Following Prostate

  8. Establishing an in vivo model of canine prostate carcinoma using the new cell line CT1258

    Winkler Susanne

    2008-08-01

    Full Text Available Abstract Background Prostate cancer is a frequent finding in man. In dogs, malignant disease of the prostate is also of clinical relevance, although it is a less common diagnosis. Even though there are numerous differences in origin and development of the disease, man and dog share many similarities in the pathological presentation. For this reason, the dog might be a useful animal model for prostate malignancies in man. Although prostate cancer is of great importance in veterinary medicine as well as in comparative medicine, there are only few cell lines available. Thus, it was the aim of the present study to determine whether the formerly established prostate carcinoma cell line CT1258 is a suitable tool for in vivo testing, and to distinguish the growth pattern of the induced tumours. Methods For characterisation of the in vivo behaviour of the in vitro established canine prostate carcinoma cell line CT1258, cells were inoculated in 19 NOD.CB17-PrkdcScid/J (in the following: NOD-Scid mice, either subcutaneously or intraperitoneally. After sacrifice, the obtained specimens were examined histologically and compared to the pattern of the original tumour in the donor. Cytogenetic investigation was performed. Results The cell line CT 1258 not only showed to be highly tumourigenic after subcutaneous as well as intraperitoneal inoculation, but also mimicked the behaviour of the original tumour. Conclusion Tumours induced by inoculation of the cell line CT1258 resemble the situation in naturally occurring prostate carcinoma in the dog, and thus could be used as in vivo model for future studies.

  9. Prediction of response to preoperative chemoradiotherapy and establishment of individualized therapy in advanced rectal cancer.

    Nakao, Toshihiro; Iwata, Takashi; Hotchi, Masanori; Yoshikawa, Kozo; Higashijima, Jun; Nishi, Masaaki; Takasu, Chie; Eto, Shohei; Teraoku, Hiroki; Shimada, Mitsuo

    2015-10-01

    Preoperative chemoradiotherapy (CRT) has become the standard treatment for patients with locally advanced rectal cancer. However, no specific biomarker has been identified to predict a response to preoperative CRT. The aim of the present study was to assess the gene expression patterns of patients with advanced rectal cancer to predict their responses to preoperative CRT. Fifty-nine rectal cancer patients were subjected to preoperative CRT. Patients were randomly assigned to receive CRT with tegafur/gimeracil/oteracil (S-1 group, n=30) or tegafur-uracil (UFT group, n=29). Gene expression changes were studied with cDNA and miRNA microarray. The association between gene expression and response to CRT was evaluated. cDNA microarray showed that 184 genes were significantly differentially expressed between the responders and the non‑responders in the S-1 group. Comparatively, 193 genes were significantly differentially expressed in the responders in the UFT group. TBX18 upregulation was common to both groups whereas BTNL8, LOC375010, ADH1B, HRASLS2, LOC284232, GCNT3 and ALDH1A2 were significantly differentially lower in both groups when compared with the non-responders. Using miRNA microarray, we found that 7 and 16 genes were significantly differentially expressed between the responders and non-responders in the S-1 and UFT groups, respectively. miR-223 was significantly higher in the responders in the S-1 group and tended to be higher in the responders in the UFT group. The present study identified several genes likely to be useful for establishing individualized therapies for patients with rectal cancer.

  10. Presenting an Evaluation Model for the Cancer Registry Software.

    Moghaddasi, Hamid; Asadi, Farkhondeh; Rabiei, Reza; Rahimi, Farough; Shahbodaghi, Reihaneh

    2017-12-01

    As cancer is increasingly growing, cancer registry is of great importance as the main core of cancer control programs, and many different software has been designed for this purpose. Therefore, establishing a comprehensive evaluation model is essential to evaluate and compare a wide range of such software. In this study, the criteria of the cancer registry software have been determined by studying the documents and two functional software of this field. The evaluation tool was a checklist and in order to validate the model, this checklist was presented to experts in the form of a questionnaire. To analyze the results of validation, an agreed coefficient of %75 was determined in order to apply changes. Finally, when the model was approved, the final version of the evaluation model for the cancer registry software was presented. The evaluation model of this study contains tool and method of evaluation. The evaluation tool is a checklist including the general and specific criteria of the cancer registry software along with their sub-criteria. The evaluation method of this study was chosen as a criteria-based evaluation method based on the findings. The model of this study encompasses various dimensions of cancer registry software and a proper method for evaluating it. The strong point of this evaluation model is the separation between general criteria and the specific ones, while trying to fulfill the comprehensiveness of the criteria. Since this model has been validated, it can be used as a standard to evaluate the cancer registry software.

  11. Patentability aspects of computational cancer models

    Lishchuk, Iryna

    2017-07-01

    Multiscale cancer models, implemented in silico, simulate tumor progression at various spatial and temporal scales. Having the innovative substance and possessing the potential of being applied as decision support tools in clinical practice, patenting and obtaining patent rights in cancer models seems prima facie possible. What legal hurdles the cancer models need to overcome for being patented we inquire from this paper.

  12. Round one of the Adelaide and Meath Hospital/Trinity College Colorectal Cancer Screening Programme: programme report and analysis based on established international key performance indices.

    McNamara, D

    2012-02-01

    BACKGROUND: In Ireland, colorectal cancer (CRC) is the second most frequently diagnosed cancer in men, after prostate cancer, and the second most frequently diagnosed cancer in women, after breast cancer. By 2020, the number of new cases diagnosed annually in Ireland is projected to have increased by 79% in men and 56% in women. Organised screening for CRC is already underway or is in the process of being rolled out in several European countries, either at a regional or national level. The Adelaide and Meath Hospital\\/ Trinity College Dublin Colorectal Cancer Screening Programme (TTC-CRC-SP) is Ireland\\'s first pilot population based bowel screening programme. METHOD: Based on a biennial test model the pilot aimed to assess the accuracy of FIT and to evaluate the whole programme based on established international key performance indices. RESULTS: To date 9,993 individuals aged 50-74 years have been invited to participate in the TTC-CRC-SP with over 5,000 FIT\\'s analysed. Overall uptake was 51% and FIT positivity was 10%. The programme has undertaken over 400 screening colonoscopies and detected 154 precancerous adenomas and 38 cancerous lesions. CONCLUSIONS: The first round of The Adelaide and Meath Hospital Tallaght\\/Trinity College Dublin Colorectal Cancer Screening Programme has been highly successful and confirmed that there is an advantage for FIT based two stage bowel cancer screening programmes.

  13. Establishment of a chronic activity-based anorexia rat model

    Frintrop, Linda; Trinh, Stefanie; Liesbrock, Johanna; Paulukat, Lisa; Kas, Martien J; Tolba, Rene; Konrad, Kerstin; Herpertz-Dahlmann, Beate; Beyer, Cordian; Seitz, Jochen

    2018-01-01

    BACKGROUND: Anorexia nervosa (AN) is often a chronic eating disorder characterised by body image disturbance and low body weight often associated with starvation-induced amenorrhoea and excessive exercise. Activity-based anorexia (ABA) is an animal model representing many somatic aspects of this

  14. Establishment of a chronic activity-based anorexia rat model

    Frintrop, Linda; Trinh, Stefanie; Liesbrock, Johanna; Paulukat, Lisa; Kas, Martien J.; Tolba, Rene; Konrad, Kerstin; Herpertz-Dahlmann, Beate; Beyer, Cordian; Seitz, Jochen

    2018-01-01

    AbstractBackground Anorexia nervosa (AN) is often a chronic eating disorder characterised by body image disturbance and low body weight often associated with starvation-induced amenorrhoea and excessive exercise. Activity-based anorexia (ABA) is an animal model representing many somatic aspects of

  15. A Model for Establishing an Astronomy Education Discussion Group

    Deming, Grace; Hayes-Gehrke, M.; Zauderer, B. A.; Bovill, M. S.; DeCesar, M.

    2010-01-01

    In October 2005, a group of astronomy faculty and graduate students met to establish departmental support for participants in the UM Center for Teaching Excellence University Teaching and Learning Program. This program seeks to increase graduate students’ understanding of effective teaching methods, awareness of student learning, and appreciation of education as a scholarly pursuit. Our group has facilitated the submission of successful graduate student educational development grant proposals to the Center for Teaching Excellence (CTE). Completion of the CTE program results in a notation on the graduate student's transcript. Our discussion group met monthly during the first two years. The Astronomy Education Review, The Physics Teacher, The Washington Post, The Chronicle of Higher Education, and National Research Council publications were used to provide background for discussion. Beginning in 2007, the group began sponsoring monthly astronomy education lunches during the academic year to which the entire department was invited. Over the past two years, speakers have included graduate students, faculty, and guests, such as Jay Labov from the National Research Council. Topics have included the Astronomy Diagnostic Test, intelligent design versus evolution, active learning techniques, introducing the use of lecture tutorials, using effective demonstrations, confronting student misconceptions, engagement through clickers (or cards), and fostering critical thinking with ranking tasks. The results of an informal evaluation will be presented.

  16. Establishment of a normal-derived estrogen receptor-positive cell line comparable to the prevailing human breast cancer subtype

    Hopkinson, Branden Michael; Klitgaard, Marie Christine; Petersen, Ole William

    2017-01-01

    Understanding human cancer increasingly relies on insight gained from subtype specific comparisons between malignant and non-malignant cells. The most frequent subtype in breast cancer is the luminal. By far the most frequently used model for luminal breast cancer is the iconic estrogen receptor-...

  17. Establishing a Cloud Computing Success Model for Hospitals in Taiwan

    Lian, Jiunn-Woei

    2017-01-01

    The purpose of this study is to understand the critical quality-related factors that affect cloud computing success of hospitals in Taiwan. In this study, private cloud computing is the major research target. The chief information officers participated in a questionnaire survey. The results indicate that the integration of trust into the information systems success model will have acceptable explanatory power to understand cloud computing success in the hospital. Moreover, information quality and system quality directly affect cloud computing satisfaction, whereas service quality indirectly affects the satisfaction through trust. In other words, trust serves as the mediator between service quality and satisfaction. This cloud computing success model will help hospitals evaluate or achieve success after adopting private cloud computing health care services. PMID:28112020

  18. Establishing a Cloud Computing Success Model for Hospitals in Taiwan.

    Lian, Jiunn-Woei

    2017-01-01

    The purpose of this study is to understand the critical quality-related factors that affect cloud computing success of hospitals in Taiwan. In this study, private cloud computing is the major research target. The chief information officers participated in a questionnaire survey. The results indicate that the integration of trust into the information systems success model will have acceptable explanatory power to understand cloud computing success in the hospital. Moreover, information quality and system quality directly affect cloud computing satisfaction, whereas service quality indirectly affects the satisfaction through trust. In other words, trust serves as the mediator between service quality and satisfaction. This cloud computing success model will help hospitals evaluate or achieve success after adopting private cloud computing health care services.

  19. Establishing a Cloud Computing Success Model for Hospitals in Taiwan

    Jiunn-Woei Lian PhD

    2017-01-01

    Full Text Available The purpose of this study is to understand the critical quality-related factors that affect cloud computing success of hospitals in Taiwan. In this study, private cloud computing is the major research target. The chief information officers participated in a questionnaire survey. The results indicate that the integration of trust into the information systems success model will have acceptable explanatory power to understand cloud computing success in the hospital. Moreover, information quality and system quality directly affect cloud computing satisfaction, whereas service quality indirectly affects the satisfaction through trust. In other words, trust serves as the mediator between service quality and satisfaction. This cloud computing success model will help hospitals evaluate or achieve success after adopting private cloud computing health care services.

  20. On the Need to Establish an International Soil Modeling Consortium

    Vereecken, H.; Vanderborght, J.; Schnepf, A.

    2014-12-01

    Soil is one of the most critical life-supporting compartments of the Biosphere. Soil provides numerous ecosystem services such as a habitat for biodiversity, water and nutrients, as well as producing food, feed, fiber and energy. To feed the rapidly growing world population in 2050, agricultural food production must be doubled using the same land resources footprint. At the same time, soil resources are threatened due to improper management and climate change. Despite the many important functions of soil, many fundamental knowledge gaps remain, regarding the role of soil biota and biodiversity on ecosystem services, the structure and dynamics of soil communities, the interplay between hydrologic and biotic processes, the quantification of soil biogeochemical processes and soil structural processes, the resilience and recovery of soils from stress, as well as the prediction of soil development and the evolution of soils in the landscape, to name a few. Soil models have long played an important role in quantifying and predicting soil processes and related ecosystem services. However, a new generation of soil models based on a whole systems approach comprising all physical, mechanical, chemical and biological processes is now required to address these critical knowledge gaps and thus contribute to the preservation of ecosystem services, improve our understanding of climate-change-feedback processes, bridge basic soil science research and management, and facilitate the communication between science and society. To meet these challenges an international community effort is required, similar to initiatives in systems biology, hydrology, and climate and crop research. Our consortium will bring together modelers and experimental soil scientists at the forefront of new technologies and approaches to characterize soils. By addressing these aims, the consortium will contribute to improve the role of soil modeling as a knowledge dissemination instrument in addressing key

  1. Establishing a Cloud Computing Success Model for Hospitals in Taiwan

    Lian, Jiunn-Woei

    2017-01-01

    The purpose of this study is to understand the critical quality-related factors that affect cloud computing success of hospitals in Taiwan. In this study, private cloud computing is the major research target. The chief information officers participated in a questionnaire survey. The results indicate that the integration of trust into the information systems success model will have acceptable explanatory power to understand cloud computing success in the hospital. Moreover, information quality...

  2. MDA-based interoperability establishment using language independent information models

    Agostinho C.; Cerny J.; Jardim-Goncalves R.

    2012-01-01

    Part 2: Full Papers; International audience; Nowadays, more and more enterprises realize that one important step to success in their business is to create new and innovative products. Many times the solution to do that is to abandon the idea of an enterprise as an “isolated island”, and get collaboration with others: worldwide non-hierarchical networks are characterized by collaboration and non-centralized decision making. This paper proposes a conceptual model common to the entire business n...

  3. Human Cancer Models Initiative | Office of Cancer Genomics

    The Human Cancer Models Initiative (HCMI) is an international consortium that is generating novel human tumor-derived culture models, which are annotated with genomic and clinical data. In an effort to advance cancer research and more fully understand how in vitro findings are related to clinical biology, HCMI-developed models and related data will be available as a community resource for cancer research.

  4. Personalized medicine for cystic fibrosis: establishing human model systems.

    Mou, Hongmei; Brazauskas, Karissa; Rajagopal, Jayaraj

    2015-10-01

    With over 1,500 identifiable mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene that result in distinct functional and phenotypical abnormalities, it is virtually impossible to perform randomized clinical trials to identify the best therapeutics for all patients. Therefore, a personalized medicine approach is essential. The only way to realistically accomplish this is through the development of improved in vitro human model systems. The lack of a readily available and infinite supply of human CFTR-expressing airway epithelial cells is a key bottleneck. We propose that a concerted two-pronged approach is necessary for patient-specific cystic fibrosis research to continue to prosper and realize its potential: (1) more effective culture and differentiation conditions for growing primary human airway and nasal epithelial cells and (2) the development of collective protocols for efficiently differentiating disease- and patient-specific induced pluripotent stem cells (iPSC) into pure populations of adult epithelial cells. Ultimately, we need a personalized human model system for cystic fibrosis with the capacity for uncomplicated bankability, widespread availability, and universal applicability for patient-specific disease modeling, novel pharmacotherapy investigation and screening, and readily executable genetic modification. © 2015 Wiley Periodicals, Inc.

  5. Establishing tumour tracking accuracy in free-breathing respiratory gated SBRT of lung cancer

    Wen, Chuan-Dong; Wong, C; Ackerly, T; Ruben, J; Millar, J

    2014-01-01

    Free-breathing respiratory gated SBRT of surgically inoperable lung cancer has been clinically commissioned. This study was to establish the tumour tracking accuracy under clinical conditions based on an implanted fiducial marker. A Visicoil TM marker embedded in tissue-equivalent material mounted in a phantom (ET Gating Phantom TM Brainlab) driven by a patient's breathing data was treated with the ExacTrac TM system. This one-dimensional moving marker represented a tumour motion in superior-inferior (S-I) direction measured through 4DCT study of the same patient. Both Gafchromic TM films and the stereoscopic kV images were used for tracking the position of the marker. For tumour motion at magnitudes of 10, 20 and 29 mm and treated with corresponding gate widths of 50%, 33% and 20% of free breathing amplitude, the implanted marker was able to be tracked with a deviation ≤1.53 mm to its planned position.

  6. A mathematical model of cancer cells with phenotypic plasticity

    Da Zhou

    2015-12-01

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

  7. Establishment of a porcine model of patent foramen ovale

    Jiang Weijian; Xiao Xiangsheng

    2007-01-01

    Objective: To investigate the feasibility of developing an animal model of patent foramen ovale (PFO) in piglets by percutaneous atrial septal puncture and balloon dilation. Methods: A standardized percutaneous atrial trans-septal puncture and balloon dilation was conducted in eleven healthy piglets under general anesthesia. A Rups-100 system inserted through a femoral vein was used for the trans-septal puncture, and subsequent balloon dilatation was performed at the puncture site to imitate a PFO. Euthanasia and autopsy were performed on day-1 in 1 piglet (early autopsy), and on day-21 in the remaining 10 piglets (late autopsy). Results: Artificial PFO was successfully created in all piglets and verified by fluoroscopy. No major technical difficulty or complication was encountered except in one which developed mild hemopericardium. In the piglet which had early autopsy, the artificial foramen was measured 0.8 cm x 0.7 cm in cross-section and aggregates of erythrocytes were revealed over its rim under light microscopy. In the late autopsy group (n=10), 7 piglets had the created foramens healed and sealed off; while the other 3 showed relatively small residual lumens measuring 0.1 cm x 0.2 cm, 0.2 cm x 0.2 cm and 0.1 cm x 0.3 cm in cross-section respectively. Histological examination of specimens from the late autopsy group showed variable neointima hyperplasia, loss of neointima, infiltration of lymphocytes, focal hydropic degeneration of cardiac muscle, and focal fibrosis of interstitium at the immediate vicinity of regardless of the course of healing. Conclusion: Artificial creation of PFO in piglets is feasible by percutaneous atrial septal puncture and balloon dilation. This protocol may serve as a research model for PFO-related stroke in human. (authors)

  8. Establishment of a 12-gene expression signature to predict colon cancer prognosis

    Dalong Sun

    2018-06-01

    Full Text Available A robust and accurate gene expression signature is essential to assist oncologists to determine which subset of patients at similar Tumor-Lymph Node-Metastasis (TNM stage has high recurrence risk and could benefit from adjuvant therapies. Here we applied a two-step supervised machine-learning method and established a 12-gene expression signature to precisely predict colon adenocarcinoma (COAD prognosis by using COAD RNA-seq transcriptome data from The Cancer Genome Atlas (TCGA. The predictive performance of the 12-gene signature was validated with two independent gene expression microarray datasets: GSE39582 includes 566 COAD cases for the development of six molecular subtypes with distinct clinical, molecular and survival characteristics; GSE17538 is a dataset containing 232 colon cancer patients for the generation of a metastasis gene expression profile to predict recurrence and death in COAD patients. The signature could effectively separate the poor prognosis patients from good prognosis group (disease specific survival (DSS: Kaplan Meier (KM Log Rank p = 0.0034; overall survival (OS: KM Log Rank p = 0.0336 in GSE17538. For patients with proficient mismatch repair system (pMMR in GSE39582, the signature could also effectively distinguish high risk group from low risk group (OS: KM Log Rank p = 0.005; Relapse free survival (RFS: KM Log Rank p = 0.022. Interestingly, advanced stage patients were significantly enriched in high 12-gene score group (Fisher’s exact test p = 0.0003. After stage stratification, the signature could still distinguish poor prognosis patients in GSE17538 from good prognosis within stage II (Log Rank p = 0.01 and stage II & III (Log Rank p = 0.017 in the outcome of DFS. Within stage III or II/III pMMR patients treated with Adjuvant Chemotherapies (ACT and patients with higher 12-gene score showed poorer prognosis (III, OS: KM Log Rank p = 0.046; III & II, OS: KM Log Rank p = 0.041. Among stage II/III pMMR patients

  9. Bioburden Increases Heterotopic Ossification Formation in an Established Rat Model.

    Pavey, Gabriel J; Qureshi, Ammar T; Hope, Donald N; Pavlicek, Rebecca L; Potter, Benjamin K; Forsberg, Jonathan A; Davis, Thomas A

    2015-09-01

    Heterotopic ossification (HO) develops in a majority of combat-related amputations wherein early bacterial colonization has been considered a potential early risk factor. Our group has recently developed a small animal model of trauma-induced HO that incorporates many of the multifaceted injury patterns of combat trauma in the absence of bacterial contamination and subsequent wound colonization. We sought to determine if (1) the presence of bioburden (Acinetobacter baumannii and methicillin-resistant Staphylococcus aureus [MRSA]) increases the magnitude of ectopic bone formation in traumatized muscle after amputation; and (2) what persistent effects bacterial contamination has on late microbial flora within the amputation site. Using a blast-related HO model, we exposed 48 rats to blast overpressure, femur fracture, crush injury, and subsequent immediate transfemoral amputation through the zone of injury. Control injured rats (n = 8) were inoculated beneath the myodesis with phosphate-buffered saline not containing bacteria (vehicle) and treatment rats were inoculated with 1 × 10(6) colony-forming units of A baumannii (n = 20) or MRSA (n = 20). All animals formed HO. Heterotopic ossification was determined by quantitative volumetric measurements of ectopic bone at 12-weeks postinjury using micro-CT and qualitative histomorphometry for assessment of new bone formation in the residual limb. Bone marrow and muscle tissue biopsies were collected from the residual limb at 12 weeks to quantitatively measure the bioburden load and to qualitatively determine the species-level identification of the bacterial flora. At 12 weeks, we observed a greater volume of HO in rats infected with MRSA (68.9 ± 8.6 mm(3); 95% confidence interval [CI], 50.52-85.55) when compared with A baumannii (20.9 ± 3.7 mm(3); 95% CI, 13.61-28.14; p infection but were positive for other strains of bacteria (1.33 × 10(2) ± 0.89 × 10(2); 95% CI, -0.42 × 10(2)-3.08 × 10(2) and 1.25 × 10(6) ± 0

  10. Establishment of H2Mab-119, an Anti-Human Epidermal Growth Factor Receptor 2 Monoclonal Antibody, Against Pancreatic Cancer.

    Yamada, Shinji; Itai, Shunsuke; Nakamura, Takuro; Chang, Yao-Wen; Harada, Hiroyuki; Suzuki, Hiroyoshi; Kaneko, Mika K; Kato, Yukinari

    2017-12-01

    Human epidermal growth factor receptor 2 (HER2) is overexpressed in breast cancer and is associated with poor clinical outcomes. In addition, HER2 expression has been reported in other cancers, such as gastric, colorectal, lung, and pancreatic cancers. An anti-HER2 humanized antibody, trastuzumab, leads to significant survival benefits in patients with HER2-overexpressing breast cancers and gastric cancers. Herein, we established a novel anti-HER2 monoclonal antibody (mAb), H 2 Mab-119 (IgG 1 , kappa), and characterized its efficacy against pancreatic cancers using flow cytometry, Western blot, and immunohistochemical analyses. H 2 Mab-119 reacted with pancreatic cancer cell lines, such as KLM-1, Capan-2, and MIA PaCa-2, but did not react with PANC-1 in flow cytometry analysis. Western blot analysis also revealed a moderate signal for KLM-1 and a weak signal for MIA PaCa-2, although H 2 Mab-119 reacted strongly with LN229/HER2 cells. Finally, immunohistochemical analyses with H 2 Mab-119 revealed sensitive and specific reactions against breast and colon cancers but did not react with pancreatic cancers, indicating that H 2 Mab-119 is useful for detecting HER2 overexpression in pancreatic cancers using flow cytometry and Western blot analyses.

  11. Proteomic and transcriptomic profiling of in vitro established radiation resistant oral cancer cells for identification of radioresistance related biomarkers

    Mohd Yasser; Pawar, Sagar; Teni, Tanuja

    2016-01-01

    Radiotherapy is an integral part of oral cancer treatment, either alone or in combination with surgery. But, during radiotherapy, oral tumours of a subset of patients develop radioresistance that creates major obstruction towards its efficacy. The aim of our study was to establish radioresistant cell lines from different oral subsites using clinically admissible low dose radiation and profile them by proteomic and transcriptomic approaches to identify proteins associated with radioresistance in oral cancer

  12. Organoid Models of Human and Mouse Ductal Pancreatic Cancer

    Boj, Sylvia F.; Hwang, Chang-Il; Baker, Lindsey A.; Chio, Iok In Christine; Engle, Dannielle D.; Corbo, Vincenzo; Jager, Myrthe; Ponz-Sarvise, Mariano; Tiriac, Herve; Spector, Mona S.; Gracanin, Ana; Oni, Tobiloba; Yu, Kenneth H.; van Boxtel, Ruben; Huch, Meritxell; Rivera, Keith D.; Wilson, John P.; Feigin, Michael E.; Oehlund, Daniel; Handly-Santana, Abram; Ardito-Abraham, Christine M.; Ludwig, Michael; Elyada, Ela; Alagesan, Brinda; Biffi, Giulia; Yordanov, Georgi N.; Delcuze, Bethany; Creighton, Brianna; Wright, Kevin; Park, Youngkyu; Morsink, Folkert H. M.; Molenaar, IQ; Borel Rinkes, Inne H.; Cuppen, Edwin; Hao, Yuan; Jin, Ying; Nijman, Isaac J.; Iacobuzio-Donahue, Christine; Leach, Steven D.; Pappin, Darryl J.; Hammell, Molly; Klimstra, David S.; Basturk, Olca; Hruban, Ralph H.; Offerhaus, George Johan; Vries, Robert G. J.; Clevers, Hans; Tuveson, David A.

    2015-01-01

    Pancreatic cancer is one of the most lethal malignancies due to its late diagnosis and limited response to treatment. Tractable methods to identify and interrogate pathways involved in pancreatic tumorigenesis are urgently needed. We established organoid models from normal and neoplastic murine and

  13. Evidence of gene-environment interactions between common breast cancer susceptibility loci and established environmental risk factors.

    Stefan Nickels

    Full Text Available Various common genetic susceptibility loci have been identified for breast cancer; however, it is unclear how they combine with lifestyle/environmental risk factors to influence risk. We undertook an international collaborative study to assess gene-environment interaction for risk of breast cancer. Data from 24 studies of the Breast Cancer Association Consortium were pooled. Using up to 34,793 invasive breast cancers and 41,099 controls, we examined whether the relative risks associated with 23 single nucleotide polymorphisms were modified by 10 established environmental risk factors (age at menarche, parity, breastfeeding, body mass index, height, oral contraceptive use, menopausal hormone therapy use, alcohol consumption, cigarette smoking, physical activity in women of European ancestry. We used logistic regression models stratified by study and adjusted for age and performed likelihood ratio tests to assess gene-environment interactions. All statistical tests were two-sided. We replicated previously reported potential interactions between LSP1-rs3817198 and parity (Pinteraction = 2.4 × 10(-6 and between CASP8-rs17468277 and alcohol consumption (Pinteraction = 3.1 × 10(-4. Overall, the per-allele odds ratio (95% confidence interval for LSP1-rs3817198 was 1.08 (1.01-1.16 in nulliparous women and ranged from 1.03 (0.96-1.10 in parous women with one birth to 1.26 (1.16-1.37 in women with at least four births. For CASP8-rs17468277, the per-allele OR was 0.91 (0.85-0.98 in those with an alcohol intake of <20 g/day and 1.45 (1.14-1.85 in those who drank ≥ 20 g/day. Additionally, interaction was found between 1p11.2-rs11249433 and ever being parous (Pinteraction = 5.3 × 10(-5, with a per-allele OR of 1.14 (1.11-1.17 in parous women and 0.98 (0.92-1.05 in nulliparous women. These data provide first strong evidence that the risk of breast cancer associated with some common genetic variants may vary with environmental risk factors.

  14. Establishment and characterization of a new cell line of canine inflammatory mammary cancer: IPC-366.

    Sara Caceres

    Full Text Available Canine inflammatory mammary cancer (IMC shares epidemiologic, histopathological and clinical characteristics with the disease in humans and has been proposed as a natural model for human inflammatory breast cancer (IBC. The aim of this study was to characterize a new cell line from IMC (IPC-366 for the comparative study of both IMC and IBC. Tumors cells from a female dog with clinical IMC were collected. The cells were grown under adherent conditions. The growth, cytological, ultrastructural and immunohistochemical (IHC characteristics of IPC-366 were evaluated. Ten female Balb/SCID mice were inoculated with IPC-366 cells to assess their tumorigenicity and metastatic potential. Chromosome aberration test and Karyotype revealed the presence of structural aberration, numerical and neutral rearrangements, demonstrating a chromosomal instability. Microscopic examination of tumor revealed an epithelial morphology with marked anysocytosis. Cytological and histological examination of smears and ultrathin sections by electron microscopy revealed that IPC-366 is formed by highly malignant large round or polygonal cells characterized by marked atypia and prominent nucleoli and frequent multinucleated cells. Some cells had cytoplasmic empty spaces covered by cytoplasmic membrane resembling capillary endothelial cells, a phenomenon that has been related to s vasculogenic mimicry. IHC characterization of IPC-366 was basal-like: epithelial cells (AE1/AE3+, CK14+, vimentin+, actin-, p63-, ER-, PR-, HER-2, E-cadherin, overexpressed COX-2 and high Ki-67 proliferation index (87.15 %. At 2 weeks after inoculating the IPC-366 cells, a tumor mass was found in 100 % of mice. At 4 weeks metastases in lung and lymph nodes were found. Xenograph tumors maintained the original IHC characteristics of the female dog tumor. In summary, the cell line IPC-366 is a fast growing malignant triple negative cell line model of inflammatory mammary carcinoma that can be used for the

  15. Building a better model of cancer

    DeGregori James

    2006-10-01

    Full Text Available Abstract The 2006 Cold Spring Harbor Laboratory meeting on the Mechanisms and Models of Cancer was held August 16–20. The meeting featured several hundred presentations of many short talks (mostly selected from the abstracts and posters, with the airing of a number of exciting new discoveries. We will focus this meeting review on models of cancer (primarily mouse models, highlighting recent advances in new mouse models that better recapitulate sporadic tumorigenesis, demonstrations of tumor addiction to tumor suppressor inactivation, new insight into senescence as a tumor barrier, improved understanding of the evolutionary paths of cancer development, and environmental/immunological influences on cancer.

  16. Characterization of the Chicken Ovarian Cancer Model

    Rodriguez, Gustavo

    2002-01-01

    .... Unlike other ovarian cancer models, which require experimental induction of ovarian tumors, chickens develop ovarian adenocarcinoma spontaneously, with an incidence ranging from 13 to 40 percent...

  17. Characterization of the Chicken Ovarian Cancer Model

    Rodriguez, Gustavo C

    2004-01-01

    .... Unlike other ovarian cancer models, which require experimental induction of ovarian tumors, chickens develop ovarian adenocarcinoma spontaneously, with an incidence ranging from 13 to 40 percent...

  18. Characterization of the Chicken Ovarian Cancer Model

    Rodriguez, Gustavo C

    2005-01-01

    .... Unlike other ovarian cancer models, which require experimental induction of ovarian tumors, chickens develop ovarian adenocarcinoma spontaneously, with an incidence ranging from 13 to 40 percent...

  19. Characterization of the Chicken Ovarian Cancer Model

    Rodriguez, Gustavo

    2003-01-01

    .... Unlike other ovarian cancer models, which require experimental induction of ovarian tumors, chickens develop ovarian adenocarcinoma spontaneously, with an incidence ranging from 13 to 40 percent...

  20. Characterization of the Chicken Ovarian Cancer Model

    Rodriquez, Gustavo

    2001-01-01

    .... Unlike other ovarian cancer models, which require experimental induction of ovarian tumors, chickens develop ovarian adenocarcinoma spontaneously, with an incidence ranging from 13 to 40 percent...

  1. Establishment of a radioresistant human lung cancer cell subline and its mechanism of radioresistance

    Zhao Wei; Wang Qiong; Liu Li; Shi Xing; Ding Qian; Wu Gang

    2008-01-01

    Objective: To establish a radioresistant cell subline from a human A549 lung cancer cell line and investigate the mechanism of radioresistance. Methods: Two proposals were applied for the non-small cell lung cancer A549 cells irradiated with X-rays: A group of A549 cell line was irradiated five times, the fractionated dose was 600 cGy, and the other group was exposed 15 times, the fractionated dose was 200 cGy. After the completion of irradiation, two monoclones were obtained from the survival of cells and named the subline A549-S1 and A549-S2. The radiosensitivity and cell cycle distribution of these two clones, together with its parental A549 cells were measured by clone formation assay and flow cytometry. The mRNA and protein levels of Notchl in A549 cell line and the sublines were determined by RT-PCR and Western-blots. Results: Compared with the parental A549 cells, A549-S1 cells showed significant resistance to radiation with D 0 , D q and N values increased, and a broader initial shoulder as well as 1.38-fold increased value of SF 2 . The A549-S1 subline also showed higher percentage of cells in S phase and G 2 /M phase, but lower percentages in G 1 /G 1 phase (P 0 , D q and N values decreased and a curve initial shoulder. The ratio of cells in S and G 0 /G 1 phase ratio was lower than that in parental A549 cells, but that in G 2 /M phase ratio was higher significantly (P<0.05). The expression of Notchl had no marked change compared to A549 cell. Conclusions: The radioresistance of the A549 cell subline is correlated with the irradiation program. The cell subline shows a different cell cycle distribution from their parental line. The cell cycle distribution has a close correlaiton with the expression of Notchl. (authors)

  2. Establishment and application of a multiplex genetic mutation-detection method of lung cancer based on MassARRAY platform

    Tian, Hong-Xia; Zhang, Xu-Chao; Wang, Zhen; Chen, Jian-Guang; Chen, Shi-Liang; Guo, Wei-Bang; Wu, Yi-Long

    2016-01-01

    Objective: This study aims to establish a method for highly parallel multiplexed detection of genetic mutations in Chinese lung cancer samples through Agena iPLEX chemistry and matrix-assisted laser desorption ionization time-of-flight analysis on MassARRAY mass spectrometry platform. Methods: We reviewed the related literature and data on lung cancer treatments. We also identified 99 mutation hot spots in 13 target genes closely related to the pathogenesis, drug resistance, and metastasis of lung cancer. A total of 297 primers, composed of 99 paired forward and reverse amplification primers and 99 matched extension primers, were designed using Assay Design software. The detection method was established by analyzing eight cell lines and six lung cancer specimens. The proposed method was then validated through comparisons by using a LungCarta TM kit. The sensitivity and specificity of the proposed method were evaluated by directly sequencing EGFR and KRAS genes in 100 lung cancer cases. Results: The proposed method was able to detect multiplex genetic mutations in lung cancer cell lines. This finding was consistent with the observations on previously reported mutations. The proposed method can also detect such mutations in clinical lung cancer specimens. This result was consistent with the observations with LungCarta TM kit. However, an FGFR2 mutation was detected only through the proposed method. The measured sensitivity and specificity were 100% and 96.3%, respectively. Conclusions: The proposed MassARRAY technology-based multiplex method can detect genetic mutations in Chinese lung cancer patients. Therefore, the proposed method can be applied to detect mutations in other cancer tissues

  3. Establishing and Sustaining a Prospective Screening Program for Breast Cancer-Related Lymphedema at the Massachusetts General Hospital: Lessons Learned

    Cheryl Brunelle

    2015-05-01

    Full Text Available There has been an increasing call to prospectively screen patients with breast cancer for the development of breast cancer-related lymphedema (BCRL following their breast cancer treatment. While the components of a prospective screening program have been published, some centers struggle with how to initiate, establish, and sustain a screening program of their own. The intent of this manuscript is to share our experience and struggles in establishing a prospective surveillance program within the infrastructure of our institution. It is our hope that by sharing our history other centers can learn from our mistakes and successes to better design their own prospective screening program to best serve their patient population.

  4. Establishment of a Ewing's sarcoma mouse model: JAK/STAT signalling in Ewing's sarcoma

    Sax, B.

    2011-01-01

    The Ewing's sarcoma family of tumours (ESFT) comprises paediatric cancers of bone and soft tissue which presumably originate from mesenchymal progenitor cells(MPC). One hallmark of ESFT is the presence of a chromosomal translocation. In 90% of the cases chromosome 11 fuses with chromosome 22. This translocation generates the EWS/FLI-1 fusion which acts as an aberrant transcription factor deregulating many genes involved in tumour development. Surgery and/or radiotherapy combined with chemotherapy are the usual forms of treatment for ESFT. But since there is only little progress in the field of chemotherapy the need for an animal model for pre-clinical drug testing is evident. Thus, the main focus of this thesis was to establish a mouse model that develops sarcomas resembling the phenotype of ESFT. We used a conditional EWS/FLI-1 mouse model, which upon Cre activity (controlled by a tissue specific promotor) expressed EWS/FLI-1 in the targeted cells. Since ESFT arises in bone and surrounding soft tissue we decided to direct expression of EWS/FLI-1 to the mesenchymal lineage by using different Cre lines. Only when using the Prx1Cre, double transgenic mice tolerated EWS/FLI-1 expression. We observed developmental abnormalities with severe skeletal deformations. Bone formation was impaired due to the absence of mature chondrocytes and osteoblasts and hence a lack of calcified bone. The lack of mature bone cells in EWS/FLI-1 expressing Prx1Cre mice supports in vitro data showing that EWS/FLI-1 impedes differentiation of murine mesenchymal progenitor cells. Currently, the project is extended to analysis of an inducible Prx1Cre system which circumvents the early lethality of Prx1Cre EF mice. This should provide the basis for tumour formation in these mice and hence the development of an appropriate mouse model for pre-clinical research. In the second project of my PhD thesis, the role of the Janus Kinase/Signal Transducer and Activator of Transcription (JAK

  5. Cancer Metabolism: A Modeling Perspective

    Ghaffari, Pouyan; Mardinoglu, Adil; Nielsen, Jens

    2015-01-01

    suggest that utilization of amino acids and lipids contributes significantly to cancer cell metabolism. Also recent progresses in our understanding of carcinogenesis have revealed that cancer is a complex disease and cannot be understood through simple investigation of genetic mutations of cancerous cells...

  6. Ancient Genes Establish Stress-Induced Mutation as a Hallmark of Cancer

    Cisneros, L; Bussey, K; Orr, A; Miočević, M.; Lineweaver, C; Davies, Paul

    2017-01-01

    Cancer is sometimes depicted as a reversion to single cell behavior in cells adapted to live in a multicellular assembly. If this is the case, one would expect that mutation in cancer disrupts functional mechanisms that suppress cell-level traits detrimental to multicellularity. Such mechanisms

  7. Laboratory animal models for esophageal cancer

    Dhanya Venugopalan Nair

    2016-11-01

    Full Text Available The incidence of esophageal cancer is rapidly increasing especially in developing countries. The major risk factors include unhealthy lifestyle practices such as alcohol consumption, smoking, and chewing tobacco to name a few. Diagnosis at an advanced stage and poor prognosis make esophageal cancer one of the most lethal diseases. These factors have urged further research in understanding the pathophysiology of the disease. Animal models not only aid in understanding the molecular pathogenesis of esophageal cancer but also help in developing therapeutic interventions for the disease. This review throws light on the various recent laboratory animal models for esophageal cancer.

  8. Opioid consumption before and after the establishment of a palliative medicine unit in an Egyptian cancer centre.

    Alsirafy, Samy A; Ibrahim, Noha Y; Abou-Elela, Enas N

    2012-01-01

    Opioid consumption before and after the establishment of a palliative medicine unit (PMU) in an Egyptian cancer centre was reviewed. A comparison of consumption during the year before the PMU was established to consumption during the third year after the PMU's establishment revealed that morphine consumption increased by 698 percent, fentanyl by 217 percent, and tramadol by 230 percent. Expressed in defined daily dose (DDD) and adjusted for 1,000 new cancer patients, consumption increased by 460 percent, from 4,678 DDD/1,000 new patients to 26,175 DDD/1,000 new patients. Expressed in grams of oral morphine equivalent (g OME), consumption increased by 644 percent, from 233 g OME/1,000 new patients to 1,731 g OME/1,000 new patients. The establishment of the PMU was associated with an increase in opioid consumption, especially morphine, which is an indicator of improvement in cancer pain control. The expression of opioid consumption in OME in addition to DDD may provide further information, especially when weak opioids are included in the analysis.

  9. Using Dual Fluorescence Reporting Genes to Establish an In Vivo Imaging Model of Orthotopic Lung Adenocarcinoma in Mice.

    Lai, Cheng-Wei; Chen, Hsiao-Ling; Yen, Chih-Ching; Wang, Jiun-Long; Yang, Shang-Hsun; Chen, Chuan-Mu

    2016-12-01

    Lung adenocarcinoma is characterized by a poor prognosis and high mortality worldwide. In this study, we purposed to use the live imaging techniques and a reporter gene that generates highly penetrative near-infrared (NIR) fluorescence to establish a preclinical animal model that allows in vivo monitoring of lung cancer development and provides a non-invasive tool for the research on lung cancer pathogenesis and therapeutic efficacy. A human lung adenocarcinoma cell line (A549), which stably expressed the dual fluorescence reporting gene (pCAG-iRFP-2A-Venus), was used to generate subcutaneous or orthotopic lung cancer in nude mice. Cancer development was evaluated by live imaging via the NIR fluorescent signals from iRFP, and the signals were verified ex vivo by the green fluorescence of Venus from the gross lung. The tumor-bearing mice received miR-16 nucleic acid therapy by intranasal administration to demonstrate therapeutic efficacy in this live imaging system. For the subcutaneous xenografts, the detection of iRFP fluorescent signals revealed delicate changes occurring during tumor growth that are not distinguishable by conventional methods of tumor measurement. For the orthotopic xenografts, the positive correlation between the in vivo iRFP signal from mice chests and the ex vivo green fluorescent signal from gross lung tumors and the results of the suppressed tumorigenesis by miR-16 treatment indicated that lung tumor size can be accurately quantified by the emission of NIR fluorescence. In addition, orthotopic lung tumor localization can be accurately visualized using iRFP fluorescence tomography in vivo, thus revealing the trafficking of lung tumor cells. We introduced a novel dual fluorescence lung cancer model that provides a non-invasive option for preclinical research via the use of NIR fluorescence in live imaging of lung.

  10. Esophageal Cancer: Insights from Mouse Models

    Marie-Pier Tétreault

    2015-01-01

    Full Text Available Esophageal cancer is the eighth leading cause of cancer and the sixth most common cause of cancer-related death worldwide. Despite recent advances in the development of surgical techniques in combination with the use of radiotherapy and chemotherapy, the prognosis for esophageal cancer remains poor. The cellular and molecular mechanisms that drive the pathogenesis of esophageal cancer are still poorly understood. Hence, understanding these mechanisms is crucial to improving outcomes for patients with esophageal cancer. Mouse models constitute valuable tools for modeling human cancers and for the preclinical testing of therapeutic strategies in a manner not possible in human subjects. Mice are excellent models for studying human cancers because they are similar to humans at the physiological and molecular levels and because they have a shorter gestation time and life cycle. Moreover, a wide range of well-developed technologies for introducing genetic modifications into mice are currently available. In this review, we describe how different mouse models are used to study esophageal cancer.

  11. Development of A Mouse Model of Menopausal Ovarian Cancer

    Elizabeth R. Smith

    2014-02-01

    Full Text Available Despite significant understanding of the genetic mutations involved in ovarian epithelial cancer and advances in genomic approaches for expression and mutation profiling of tumor tissues, several key questions in ovarian cancer biology remain enigmatic: the mechanism for the well-established impact of reproductive factors on ovarian cancer risk remains obscure; questions of the cell of origin of ovarian cancer continue to be debated; and the precursor lesion, sequence, or events in progression remain to be defined. Suitable mouse models should complement the analysis of human tumor tissues and may provide clues to these questions currently perplexing ovarian cancer biology.A potentially useful model is the germ cell-deficient Wv (white spotting variant mutant mouse line, which may be used to study the impact of menopausal physiology on the increased risk of ovarian cancer. The Wv mice harbor a point mutation in c-Kit that reduces the receptor tyrosine kinase activity to about 1-5% (it is not a null mutation. Homozygous Wv mutant females have a reduced ovarian germ cell reservoir at birth and the follicles are rapidly depleted upon reaching reproductive maturity, but other biological phenotypes are minimal and the mice have a normal life span. The loss of ovarian function precipitates changes in hormonal and metabolic activity that model features of menopause in humans. As a consequence of follicle depletion, the Wv ovaries develop ovarian tubular adenomas, a benign epithelial tumor corresponding to surface epithelial invaginations and papillomatosis that mark human ovarian aging. Ongoing work will test the possibility of converting the benign epithelial tubular adenomas into neoplastic tumors by addition of an oncogenic mutation, such as of Tp53, to model the genotype and biology of serous ovarian cancer.Model based on the Wv mice may have the potential to gain biological and etiological insights into ovarian cancer development and prevention.

  12. The Janus-Faced Role of Antioxidants in Cancer Cachexia: New Insights on the Established Concepts

    Mohamad Assi

    2016-01-01

    Full Text Available Chronic inflammation and excessive loss of skeletal muscle usually occur during cancer cachexia, leading to functional impairment and delaying the cure of cancer. The release of cytokines by tumor promotes the formation of reactive oxygen species (ROS, which in turn regulate catabolic pathways involved in muscle atrophy. ROS also exert a dual role within tumor itself, as they can either promote proliferation and vascularization or induce senescence and apoptosis. Accordingly, previous studies that used antioxidants to modulate these ROS-dependent mechanisms, in cancer and cancer cachexia, have obtained contradictory results, hence the need to gather the main findings of these studies and draw global conclusions in order to stimulate more oriented research in this field. Based on the literature reviewed in this paper, it appears that antioxidant supplementation is (1 beneficial in cancer cachectic patients with antioxidant deficiencies, (2 most likely harmful in cancer patients with adequate antioxidant status (i.e., lung, gastrointestinal, head and neck, and esophageal, and (3 not recommended when undergoing radiotherapy. At the moment, measuring the blood levels of antioxidants may help to identify patients with systemic deficiencies. This approach is simple to realize but could not be a gold standard method for cachexia, as it does not necessarily reflect the redox state in other organs, like muscle.

  13. The Janus-Faced Role of Antioxidants in Cancer Cachexia: New Insights on the Established Concepts

    Rébillard, Amélie

    2016-01-01

    Chronic inflammation and excessive loss of skeletal muscle usually occur during cancer cachexia, leading to functional impairment and delaying the cure of cancer. The release of cytokines by tumor promotes the formation of reactive oxygen species (ROS), which in turn regulate catabolic pathways involved in muscle atrophy. ROS also exert a dual role within tumor itself, as they can either promote proliferation and vascularization or induce senescence and apoptosis. Accordingly, previous studies that used antioxidants to modulate these ROS-dependent mechanisms, in cancer and cancer cachexia, have obtained contradictory results, hence the need to gather the main findings of these studies and draw global conclusions in order to stimulate more oriented research in this field. Based on the literature reviewed in this paper, it appears that antioxidant supplementation is (1) beneficial in cancer cachectic patients with antioxidant deficiencies, (2) most likely harmful in cancer patients with adequate antioxidant status (i.e., lung, gastrointestinal, head and neck, and esophageal), and (3) not recommended when undergoing radiotherapy. At the moment, measuring the blood levels of antioxidants may help to identify patients with systemic deficiencies. This approach is simple to realize but could not be a gold standard method for cachexia, as it does not necessarily reflect the redox state in other organs, like muscle. PMID:27642498

  14. Establishment of Approximate Analytical Model of Oil Film Force for Finite Length Tilting Pad Journal Bearings

    Yongliang Wang

    2015-01-01

    Full Text Available Tilting pad bearings offer unique dynamic stability enabling successful deployment of high-speed rotating machinery. The model of dynamic stiffness, damping, and added mass coefficients is often used for rotordynamic analyses, and this method does not suffice to describe the dynamic behaviour due to the nonlinear effects of oil film force under larger shaft vibration or vertical rotor conditions. The objective of this paper is to present a nonlinear oil force model for finite length tilting pad journal bearings. An approximate analytic oil film force model was established by analysing the dynamic characteristic of oil film of a single pad journal bearing using variable separation method under the dynamic π oil film boundary condition. And an oil film force model of a four-tilting-pad journal bearing was established by using the pad assembly technique and considering pad tilting angle. The validity of the model established was proved by analyzing the distribution of oil film pressure and the locus of journal centre for tilting pad journal bearings and by comparing the model established in this paper with the model established using finite difference method.

  15. Breast cancer risks and risk prediction models.

    Engel, Christoph; Fischer, Christine

    2015-02-01

    BRCA1/2 mutation carriers have a considerably increased risk to develop breast and ovarian cancer. The personalized clinical management of carriers and other at-risk individuals depends on precise knowledge of the cancer risks. In this report, we give an overview of the present literature on empirical cancer risks, and we describe risk prediction models that are currently used for individual risk assessment in clinical practice. Cancer risks show large variability between studies. Breast cancer risks are at 40-87% for BRCA1 mutation carriers and 18-88% for BRCA2 mutation carriers. For ovarian cancer, the risk estimates are in the range of 22-65% for BRCA1 and 10-35% for BRCA2. The contralateral breast cancer risk is high (10-year risk after first cancer 27% for BRCA1 and 19% for BRCA2). Risk prediction models have been proposed to provide more individualized risk prediction, using additional knowledge on family history, mode of inheritance of major genes, and other genetic and non-genetic risk factors. User-friendly software tools have been developed that serve as basis for decision-making in family counseling units. In conclusion, further assessment of cancer risks and model validation is needed, ideally based on prospective cohort studies. To obtain such data, clinical management of carriers and other at-risk individuals should always be accompanied by standardized scientific documentation.

  16. Effects of Valenced Media Frames of Cancer Diagnoses and Therapies: Quantifying the Transformation and Establishing of Evaluative Schemas.

    Guenther, Lars; Froehlich, Klara; Milde, Jutta; Heidecke, Gitte; Ruhrmann, Georg

    2015-01-01

    Journalists portray health issues within different frames, which may shape news recipients' evaluations, attitudes, and behaviors. As the research on framing continues to face theoretical challenges and methodological concerns, this study examines the transformation and establishing of evaluative schemas, which are steps in the process toward attitudinal change. The study measures recipients' evaluations of actual television clips dealing with cancer diagnoses and cancer therapies. Two valenced (positive vs. negative) media frames were tested in a 3-week online panel (n = 298) using a pretest-posttest design with a German sample. The results offer limited support for the hypothesis that media frames transform participants' schemas, but do not support the hypothesis that new schemas are established in response to media frames. The study also investigates interactions between framing and participants' issue involvement, as well as between framing and topic-specific interest and media use.

  17. The strategic case for establishing public-private partnerships in cancer care.

    Holden, Debra J; Reiter, Kristin; O'Brien, Donna; Dalton, Kathleen

    2015-10-14

    In 2007, the National Cancer Institute (NCI) launched the NCI Community Cancer Centers Program (NCCCP) as a public-private partnership with community hospitals with a goal of advancing cancer care and research. In order to leverage federal dollars in a time of limited resources, matching funds from each participating hospital were required. The purpose of this paper is to examine hospitals' level of and rationale for co-investment in this partnership, and whether there is an association between hospitals' co-investment and achievement of strategic goals. Analysis using a comparative case study and micro-cost data was conducted as part of a comprehensive evaluation of the NCCCP pilot to determine the level of co-investment made in support of NCI's goals. In-person or telephone interviews with key informants were conducted at 10 participating hospital and system sites during the first and final years of implementation. Micro-cost data were collected annually from each site from 2007 to 2010. Self-reported data from each awardee are presented on patient volume and physician counts, while secondary data are used to examine the local Medicare market share. The rationale expressed by interviewees for participation in a public-private partnership with NCI included expectations of increased market share, higher patient volumes, and enhanced opportunities for cancer physician recruitment as a result of affiliation with the NCI. On average, hospitals invested resources into the NCCCP at a level exceeding $3 for every $1 of federal funds. Six sites experienced a statistically significant change in their Medicare market share. Cancer patient volume increased by as much as one-third from Year 1 to Year 3 for eight of the sites. Nine sites reported an increase in key cancer physician recruitment. Demonstrated investments in cancer care and research were associated with increases in cancer patient volume and perhaps in recruitment of key cancer physicians, but not in increased

  18. Canadian Cancer Risk Management Model: evaluation of cancer control.

    Evans, William K; Wolfson, Michael C; Flanagan, William M; Shin, Janey; Goffin, John; Miller, Anthony B; Asakawa, Keiko; Earle, Craig; Mittmann, Nicole; Fairclough, Lee; Oderkirk, Jillian; Finès, Philippe; Gribble, Stephen; Hoch, Jeffrey; Hicks, Chantal; Omariba, D Walter R; Ng, Edward

    2013-04-01

    The aim of this study was to develop a decision support tool to assess the potential benefits and costs of new healthcare interventions. The Canadian Partnership Against Cancer (CPAC) commissioned the development of a Cancer Risk Management Model (CRMM)--a computer microsimulation model that simulates individual lives one at a time, from birth to death, taking account of Canadian demographic and labor force characteristics, risk factor exposures, and health histories. Information from all the simulated lives is combined to produce aggregate measures of health outcomes for the population or for particular subpopulations. The CRMM can project the population health and economic impacts of cancer control programs in Canada and the impacts of major risk factors, cancer prevention, and screening programs and new cancer treatments on population health and costs to the healthcare system. It estimates both the direct costs of medical care, as well as lost earnings and impacts on tax revenues. The lung and colorectal modules are available through the CPAC Web site (www.cancerview.ca/cancerrriskmanagement) to registered users where structured scenarios can be explored for their projected impacts. Advanced users will be able to specify new scenarios or change existing modules by varying input parameters or by accessing open source code. Model development is now being extended to cervical and breast cancers.

  19. Promoting Model-based Definition to Establish a Complete Product Definition.

    Ruemler, Shawn P; Zimmerman, Kyle E; Hartman, Nathan W; Hedberg, Thomas; Feeny, Allison Barnard

    2017-05-01

    The manufacturing industry is evolving and starting to use 3D models as the central knowledge artifact for product data and product definition, or what is known as Model-based Definition (MBD). The Model-based Enterprise (MBE) uses MBD as a way to transition away from using traditional paper-based drawings and documentation. As MBD grows in popularity, it is imperative to understand what information is needed in the transition from drawings to models so that models represent all the relevant information needed for processes to continue efficiently. Finding this information can help define what data is common amongst different models in different stages of the lifecycle, which could help establish a Common Information Model. The Common Information Model is a source that contains common information from domain specific elements amongst different aspects of the lifecycle. To help establish this Common Information Model, information about how models are used in industry within different workflows needs to be understood. To retrieve this information, a survey mechanism was administered to industry professionals from various sectors. Based on the results of the survey a Common Information Model could not be established. However, the results gave great insight that will help in further investigation of the Common Information Model.

  20. A methodology to establish the appearance of cancer cases due to radiation dose in compressed breast

    Feital, Joao Carlos Da Silva; Delgado, Jose Ubiratan; Peixoto, Jose Guilherme P.; Fonseca, Hugo Geraldo Da

    2013-01-01

    It is known that more than 20% of the world's population will contract some type of cancer. In Brazil, with the exception of skin cancer (non melanoma) the breast cancer ranks first among the higher frequency of tumours among women and in general, although the methods of detection are advancing in the year 2010 took place about 13 thousand deaths in about 50,000 cases, probably due to late detection of these neoplasm. New cases of breast cancer in a given population can be proven from absorbed dose quantity, calculated for the compressed breast, due to the risk by means of exposure to x rays in this radiodiagnostic practices. Methodology: Exposures were held in an ionization chamber and the other quantities required were obtained to the screen-film equipment of mammography. Results: Also experimental results were of compressed breast an equivalent dose of ( 1.82 mSv ± 0.2%) or (3.64 mSv ± 0.2%) for both projections, i.e. medium lateral oblique and cranio caudal. The experimental value obtained here is consistent with the calculated results and published in the literature for analog and CR equipment. Conclusion: From the result of dose equivalent in the breast, one can say that there will be effectively attesting as to the appearance of new cases of cancer if approximately 80 million women are exposed to radiation emitted by mammographers. (author)

  1. The establishment of bilateral external iliac artery stenosis model in experimental canines and its angiographic evaluation

    Xia Yonghui; Li Weixiao; Bi Yonghua; Xu Ke

    2011-01-01

    Objective: To establish an experimental canine model of bilateral external iliac artery stenosis by surgical method with absorbable suture. Methods: Under general anesthesia bilateral external iliac arteries were partly obstructed (about 50%) with absorbable suture in ten dogs. Three months later angiography was performed to evaluate the arterial stricture degree. Results: Bilateral external iliac artery stenosis model was successfully established in eight dogs and the other two dogs died within two weeks after the procedure. Angiography performed three months after the procedure showed that the stricture degree of arterial lumen was (60.6±12.5)%. Conclusion: Satisfactory experimental canine model of bilateral external iliac artery stenosis can be established by surgical method with absorbable suture. This method can be used for reference when peripheral artery stenosis model is to be prepared in larger animals. (authors)

  2. Learning while (re-)configuring: business model innovation processes in established firms

    Berends, J.J.; Smits, A.; Reymen, I.M.M.J.; Podoynitsyna, K.S.

    2016-01-01

    This study addresses the question of how established organizations develop new business models over time, using a process research approach to trace how four business model innovation trajectories unfold. With organizational learning as analytical lens, we discern two process patterns: “drifting”

  3. Establishment of human patient-derived endometrial cancer xenografts in NOD scid gamma mice for the study of invasion and metastasis.

    Kenji Unno

    Full Text Available Most endometrial cancers are detected early and have a good prognosis, while some endometrial cancers are highly invasive, metastasize early, and respond suboptimally to therapy. Currently, appropriate model systems to study the aggressive nature of these tumors are lacking. The objective of this study was to establish a mouse xenograft model of endometrial tumors derived from patients in order to study the biological aggressive characteristics that underlie invasion and metastasis.Endometrial tumor tissue fragments (1.5 mm × 1.5 mm from patients undergoing surgery, were transplanted under the renal capsule of NOD scid gamma mice. After 6-8 weeks, tumors were excised and serially transplanted into additional mice for propagation. Immunohistochemical analysis of the tumors was done for various tumor markers.Four cases of different subtypes of endometrial cancer were grown and propagated in mice. Three of the four tumor cases invaded into the kidneys and to adjacent organs. While all tumors exhibited minimal to no staining for estrogen receptor α, progesterone receptor staining was observed for tumor grafts. In addition, levels and localization of E-cadherin, cytokeratin and vimentin varied depending on subtype. Finally, all tumor xenografts stained positively for urokinase plasminogen activator while 3 tumor xenografts, which showed invasive characteristics, stained positively for urokinase plasminogen activator receptor.Endometrial tumors transplanted under the renal capsule exhibit growth, invasion and local spread. These tumors can be propagated and used to study aggressive endometrial cancer.

  4. Establishment and Analysis of Cancer Stem-Like and Non-Cancer Stem-Like Clone Cells from the Human Colon Cancer Cell Line SW480.

    Akari Takaya

    Full Text Available Human cancer stem-like cells (CSCs/cancer-initiating cells (CICs can be isolated as side population (SP cells, aldehyde dehydrogenase high (ALDHhigh cells or cell surface marker-positive cells including CD44+ cells and CD133+ cells. CSCs/CICs and non-CSCs/CICs are unstable in in vitro culture, and CSCs/CICs can differentiate into non-CSCs/CICs and some non-CSCs/CICs can dedifferentiate into CSCs/CICs. Therefore, experiments using a large amount of CSCs/CICs are technically very difficult. In this study, we isolated single cell clones from SP cells and main population (MP cells derived from the human colon cancer cell line SW480. SP analysis revealed that SP clone cells had relatively high percentages of SP cells, whereas MP clone cells showed very few SP cells, and the phenotypes were sustainable for more than 2 months of in vitro culture. Xenograft transplantation revealed that SP clone cells have higher tumor-initiating ability than that of MP clone cells and SP clone cell showed higher chemo-resistance compared with MP clone cells. These results indicate that SP clone cells derived from SW480 cells are enriched with CSCs/CICs, whereas MP clone cells are pure non-CSCs/CICs. SP clone cells and MP clone cells are a very stable in vitro CSC/CIC-enriched and non-CSC/CIC model for further analysis.

  5. Establishment and Analysis of Cancer Stem-Like and Non-Cancer Stem-Like Clone Cells from the Human Colon Cancer Cell Line SW480.

    Takaya, Akari; Hirohashi, Yoshihiko; Murai, Aiko; Morita, Rena; Saijo, Hiroshi; Yamamoto, Eri; Kubo, Terufumi; Nakatsugawa, Munehide; Kanaseki, Takayuki; Tsukahara, Tomohide; Tamura, Yasuaki; Takemasa, Ichiro; Kondo, Toru; Sato, Noriyuki; Torigoe, Toshihiko

    2016-01-01

    Human cancer stem-like cells (CSCs)/cancer-initiating cells (CICs) can be isolated as side population (SP) cells, aldehyde dehydrogenase high (ALDHhigh) cells or cell surface marker-positive cells including CD44+ cells and CD133+ cells. CSCs/CICs and non-CSCs/CICs are unstable in in vitro culture, and CSCs/CICs can differentiate into non-CSCs/CICs and some non-CSCs/CICs can dedifferentiate into CSCs/CICs. Therefore, experiments using a large amount of CSCs/CICs are technically very difficult. In this study, we isolated single cell clones from SP cells and main population (MP) cells derived from the human colon cancer cell line SW480. SP analysis revealed that SP clone cells had relatively high percentages of SP cells, whereas MP clone cells showed very few SP cells, and the phenotypes were sustainable for more than 2 months of in vitro culture. Xenograft transplantation revealed that SP clone cells have higher tumor-initiating ability than that of MP clone cells and SP clone cell showed higher chemo-resistance compared with MP clone cells. These results indicate that SP clone cells derived from SW480 cells are enriched with CSCs/CICs, whereas MP clone cells are pure non-CSCs/CICs. SP clone cells and MP clone cells are a very stable in vitro CSC/CIC-enriched and non-CSC/CIC model for further analysis.

  6. Mathematical Models of Breast and Ovarian Cancers

    Botesteanu, Dana-Adriana; Lipkowitz, Stanley; Lee, Jung-Min; Levy, Doron

    2016-01-01

    Women constitute the majority of the aging United States (US) population, and this has substantial implications on cancer population patterns and management practices. Breast cancer is the most common women's malignancy, while ovarian cancer is the most fatal gynecological malignancy in the US. In this review we focus on these subsets of women's cancers, seen more commonly in postmenopausal and elderly women. In order to systematically investigate the complexity of cancer progression and response to treatment in breast and ovarian malignancies, we assert that integrated mathematical modeling frameworks viewed from a systems biology perspective are needed. Such integrated frameworks could offer innovative contributions to the clinical women's cancers community, since answers to clinical questions cannot always be reached with contemporary clinical and experimental tools. Here, we recapitulate clinically known data regarding the progression and treatment of the breast and ovarian cancers. We compare and contrast the two malignancies whenever possible, in order to emphasize areas where substantial contributions could be made by clinically inspired and validated mathematical modeling. We show how current paradigms in the mathematical oncology community focusing on the two malignancies do not make comprehensive use of, nor substantially reflect existing clinical data, and we highlight the modeling areas in most critical need of clinical data integration. We emphasize that the primary goal of any mathematical study of women's cancers should be to address clinically relevant questions. PMID:27259061

  7. Extinction models for cancer stem cell therapy

    Sehl, Mary; Zhou, Hua; Sinsheimer, Janet S.; Lange, Kenneth L.

    2012-01-01

    Cells with stem cell-like properties are now viewed as initiating and sustaining many cancers. This suggests that cancer can be cured by driving these cancer stem cells to extinction. The problem with this strategy is that ordinary stem cells are apt to be killed in the process. This paper sets bounds on the killing differential (difference between death rates of cancer stem cells and normal stem cells) that must exist for the survival of an adequate number of normal stem cells. Our main tools are birth–death Markov chains in continuous time. In this framework, we investigate the extinction times of cancer stem cells and normal stem cells. Application of extreme value theory from mathematical statistics yields an accurate asymptotic distribution and corresponding moments for both extinction times. We compare these distributions for the two cell populations as a function of the killing rates. Perhaps a more telling comparison involves the number of normal stem cells NH at the extinction time of the cancer stem cells. Conditioning on the asymptotic time to extinction of the cancer stem cells allows us to calculate the asymptotic mean and variance of NH. The full distribution of NH can be retrieved by the finite Fourier transform and, in some parameter regimes, by an eigenfunction expansion. Finally, we discuss the impact of quiescence (the resting state) on stem cell dynamics. Quiescence can act as a sanctuary for cancer stem cells and imperils the proposed therapy. We approach the complication of quiescence via multitype branching process models and stochastic simulation. Improvements to the τ-leaping method of stochastic simulation make it a versatile tool in this context. We conclude that the proposed therapy must target quiescent cancer stem cells as well as actively dividing cancer stem cells. The current cancer models demonstrate the virtue of attacking the same quantitative questions from a variety of modeling, mathematical, and computational perspectives

  8. A Mouse Model for Human Anal Cancer

    Stelzer, Marie K.; Pitot, Henry C.; Liem, Amy; Schweizer, Johannes; Mahoney, Charles; Lambert, Paul F.

    2010-01-01

    Human anal cancers are associated with high-risk human papillomaviruses (HPVs) that cause other anogenital cancers and head and neck cancers. As with other cancers, HPV16 is the most common high-risk HPV in anal cancers. We describe the generation and characterization of a mouse model for human anal cancer. This model makes use of K14E6 and K14E7 transgenic mice in which the HPV16 E6 and E7 genes are directed in their expression to stratified squamous epithelia. HPV16 E6 and E7 possess oncogenic properties including but not limited to their capacity to inactivate the cellular tumor suppressors p53 and pRb, respectively. Both E6 and E7 were found to be functionally expressed in the anal epithelia of K14E6/K14E7 transgenic mice. To assess the susceptibility of these mice to anal cancer, mice were treated topically with dimethylbenz[a]anthracene (DMBA), a chemical carcinogen that is known to induce squamous cell carcinomas in other sites. Nearly 50% of DMBA-treated HPV16 E6/E7 transgenic mice showed overt signs of tumors; whereas, none of the like treated non-transgenic mice showed tumors. Histopathological analyses confirmed that the HPV16 transgenic mice were increased in their susceptibility to anal cancers and precancerous lesions. Biomarker analyses demonstrated that these mouse anal cancers exhibit properties that are similar to those observed in HPV-positive precursors to human anal cancer. This is the first mouse model for investigating the contributions of viral and cellular factors in anal carcinogenesis, and should provide a platform for assessing new therapeutic modalities for treating and/or preventing this type of cancer. PMID:20947489

  9. Establishing experimental model of human internal carotid artery siphon segment in canine common carotid artery

    Cui Xuee; Li Minghua; Wang Yongli; Cheng Yingsheng; Li Wenbin

    2005-01-01

    Objective: To study the feasibility of establishing experimental model of human internal carotid artery siphon segment in canine common carotid artery (CCA) by end-to-end anastomoses of one side common carotid artery segment with the other side common carotid artery. Methods: Surgical techniques were used to make siphon model in 8 canines. One side CCA was taken as the parent artery and anastomosing with the cut off contra-lateral CCA segment which has passed through within the S-shaped glass tube. Two weeks after the creation of models angiography showed the model siphons were patent. Results: Experimental models of human internal carotid artery siphon segment were successfully made in all 8 dogs. Conclusions: It is practically feasible to establish experimental canine common carotid artery models of siphon segment simulating human internal carotid artery. (authors)

  10. Genome scale metabolic modeling of cancer

    Nilsson, Avlant; Nielsen, Jens

    2017-01-01

    of metabolism which allows simulation and hypotheses testing of metabolic strategies. It has successfully been applied to many microorganisms and is now used to study cancer metabolism. Generic models of human metabolism have been reconstructed based on the existence of metabolic genes in the human genome......Cancer cells reprogram metabolism to support rapid proliferation and survival. Energy metabolism is particularly important for growth and genes encoding enzymes involved in energy metabolism are frequently altered in cancer cells. A genome scale metabolic model (GEM) is a mathematical formalization...

  11. Establishment of a rat model of early-stage liver failure and Th17/Treg imbalance

    LI Dong; LU Zhonghua; GAN Jianhe

    2016-01-01

    ObjectiveTo investigate the methods for establishing a rat model of early-stage liver failure and the changes in Th17, Treg, and Th17/Treg after dexamethasone and thymosin interventions. MethodsA total of 64 rats were randomly divided into carbon tetrachloride (CCl4) group and endotoxin [lipopolysaccharide (LPS)]/D-galactosamine (D-GalN) combination group to establish the rat model of early-stage liver failure. The activities of the rats and changes in liver function and whole blood Th17 and ...

  12. Establishing an Improved Kane Dynamic Model for the 7-DOF Reconfigurable Modular Robot

    Xiao Li

    2017-01-01

    Full Text Available We propose an improved Kane dynamic model theory for the 7-DOF modular robot in this paper, and the model precision is improved by the improved function T′it. We designed three types of progressive modular joints for reconfigurable modular robot that can be used in industrial robot, space robot, and special robot. The Kane dynamic model and the solid dynamic model are established, respectively, for the 7-DOF modular robot. After that, the experimental results are obtained from the simulation experiment of typical task in the established dynamic models. By the analysis model of error, the equation of the improved torque T′it is derived and proposed. And the improved Kane dynamic model is established for the modular robot that used T′it. Based on the experimental data, the undetermined coefficient matrix is five-order linear that was proved in 7-DOF modular robot. And the explicit formulation is solved of the Kane dynamic model and can be used in control system.

  13. Animal Cancer Models of Skeletal Metastasis

    Catherine Hibberd

    2013-01-01

    Full Text Available The bony skeleton is one of the most common sites of metastatic spread of cancer and is a significant source of morbidity in cancer patients, causing pain and pathologic fracture, impaired ambulatory ability, and poorer quality of life. Animal cancer models of skeletal metastases are essential for better understanding of the molecular pathways behind metastatic spread and local growth and invasion of bone, to enable analysis of host-tumor cell interactions, identify barriers to the metastatic process, and to provide platforms to develop and test novel therapies prior to clinical application in human patients. Thus, the ideal model should be clinically relevant, reproducible and representative of the human condition. This review summarizes the current in vivo animal models used in the study of cancer metastases of the skeleton.

  14. Modeling the Aneuploidy Control of Cancer

    Wang Zhong

    2010-07-01

    Full Text Available Abstract Background Aneuploidy has long been recognized to be associated with cancer. A growing body of evidence suggests that tumorigenesis, the formation of new tumors, can be attributed to some extent to errors occurring at the mitotic checkpoint, a major cell cycle control mechanism that acts to prevent chromosome missegregation. However, so far no statistical model has been available quantify the role aneuploidy plays in determining cancer. Methods We develop a statistical model for testing the association between aneuploidy loci and cancer risk in a genome-wide association study. The model incorporates quantitative genetic principles into a mixture-model framework in which various genetic effects, including additive, dominant, imprinting, and their interactions, are estimated by implementing the EM algorithm. Results Under the new model, a series of hypotheses tests are formulated to explain the pattern of the genetic control of cancer through aneuploid loci. Simulation studies were performed to investigate the statistical behavior of the model. Conclusions The model will provide a tool for estimating the effects of genetic loci on aneuploidy abnormality in genome-wide studies of cancer cells.

  15. Towards the establishment of nonlinear hidden symmetries of the Skyrme model

    Herrera-Aguilar, A.; Kanakoglou, K.; Paschalis, J. E.

    2006-01-01

    We present a preliminary attempt to establish the existence of hidden nonlinear symmetries of the SU(N) Skyrme model which could, in principle, lead to the further integration of the system. An explicit illustration is given for the SU(2) symmetry group

  16. Economical analyses of build-operate-transfer model in establishing alternative power plants

    Yumurtaci, Zehra [Yildiz Technical University, Department of Mechanical Engineering, Y.T.U. Mak. Fak. Mak. Muh. Bolumu, Besiktas, 34349 Istanbul (Turkey)]. E-mail: zyumur@yildiz.edu.tr; Erdem, Hasan Hueseyin [Yildiz Technical University, Department of Mechanical Engineering, Y.T.U. Mak. Fak. Mak. Muh. Bolumu, Besiktas, 34349 Istanbul (Turkey)

    2007-01-15

    The most widely employed method to meet the increasing electricity demand is building new power plants. The most important issue in building new power plants is to find financial funds. Various models are employed, especially in developing countries, in order to overcome this problem and to find a financial source. One of these models is the build-operate-transfer (BOT) model. In this model, the investor raises all the funds for mandatory expenses and provides financing, builds the plant and, after a certain plant operation period, transfers the plant to the national power organization. In this model, the object is to decrease the burden of power plants on the state budget. The most important issue in the BOT model is the dependence of the unit electricity cost on the transfer period. In this study, the model giving the unit electricity cost depending on the transfer of the plants established according to the BOT model, has been discussed. Unit electricity investment cost and unit electricity cost in relation to transfer period for plant types have been determined. Furthermore, unit electricity cost change depending on load factor, which is one of the parameters affecting annual electricity production, has been determined, and the results have been analyzed. This method can be employed for comparing the production costs of different plants that are planned to be established according to the BOT model, or it can be employed to determine the appropriateness of the BOT model.

  17. Economical analyses of build-operate-transfer model in establishing alternative power plants

    Yumurtaci, Zehra; Erdem, Hasan Hueseyin

    2007-01-01

    The most widely employed method to meet the increasing electricity demand is building new power plants. The most important issue in building new power plants is to find financial funds. Various models are employed, especially in developing countries, in order to overcome this problem and to find a financial source. One of these models is the build-operate-transfer (BOT) model. In this model, the investor raises all the funds for mandatory expenses and provides financing, builds the plant and, after a certain plant operation period, transfers the plant to the national power organization. In this model, the object is to decrease the burden of power plants on the state budget. The most important issue in the BOT model is the dependence of the unit electricity cost on the transfer period. In this study, the model giving the unit electricity cost depending on the transfer of the plants established according to the BOT model, has been discussed. Unit electricity investment cost and unit electricity cost in relation to transfer period for plant types have been determined. Furthermore, unit electricity cost change depending on load factor, which is one of the parameters affecting annual electricity production, has been determined, and the results have been analyzed. This method can be employed for comparing the production costs of different plants that are planned to be established according to the BOT model, or it can be employed to determine the appropriateness of the BOT model

  18. Metformin in reproductive health, pregnancy and gynaecological cancer: established and emerging indications.

    Sivalingam, Vanitha N; Myers, Jenny; Nicholas, Susie; Balen, Adam H; Crosbie, Emma J

    2014-01-01

    Metformin is an effective oral anti-hyperglycaemic drug used as first-line medical treatment for type 2 diabetes. It improves systemic hyperglycaemia by reducing hepatic glucose production and enhancing peripheral insulin sensitivity. It also stimulates fat oxidation and reduces fat synthesis and storage. The molecular mechanism of this drug is thought to be secondary to its actions on the mitochondrial respiratory chain. This paper reviews the relevant literature (research articles up to October 2013) on the use of metformin in infertility, polycystic ovary syndrome (PCOS), pregnancy and gynaecological cancers. We present a comprehensive discussion of the evidence supporting the efficacy of metformin in these clinical conditions. Metformin is used clinically off-label in the management of hirsutism, acne and insulin resistance in PCOS, although the evidence for anti-androgenic effects is inconsistent. Metformin is also used to improve ovulation in women with PCOS both alone and in combination with clomiphene citrate. Trial findings are conflicting but metformin treatment in IVF/ICSI cycles may reduce the risk of ovarian hyperstimulation syndrome and increase live birth rates. Metformin also appears to be effective and safe for the treatment of gestational diabetes mellitus (GDM), particularly for overweight and obese women. Studies have shown that metformin is safe in pregnancy and women with GDM treated with metformin have less weight gain during pregnancy than those treated with insulin. One study with a 2-year follow-up demonstrated that babies born to women treated with metformin also developed less visceral fat, making them less prone to insulin resistance in later life. These findings have sparked interest in the use of metformin for pregnant, obese, non-diabetic women. On-going clinical trials are underway to determine if women treated prophylactically with metformin have a reduced incidence of GDM and demonstrate less weight gain during pregnancy. The

  19. New BRDF Model for Desert and Gobi Using Equivalent Mirror Plane Method, Establishment and Validation

    Li, Y.; Rong, Z.

    2017-12-01

    The surface Bidirectional Reflectance Distribution Function (BRDF) is a key parameter that affects the vicarious calibration accuracy of visible channel remote sensing instrument. In the past 30 years, many studies have been made and a variety of models have been established. Among them, the Ross-li model was highly approved and widely used. Unfortunately, the model doesn't suitable for desert and Gobi quite well because of the scattering kernel it contained, needs the factors such as plant height and plant spacing. A new BRDF model for surface without vegetation, which is mainly used in remote sensing vicarious calibration, is established. That was called Equivalent Mirror Plane (EMP) BRDF. It is used to characterize the bidirectional reflectance of the near Lambertian surface. The accuracy of the EMP BRDF model is validated by the directional reflectance data measured on the Dunhuang Gobi and compared to the Ross-li model. Results show that the regression accuracy of the new model is 0.828, which is similar to the Ross-li model (0.825). Because of the simple form (contains only four polynomials) and simple principle (derived by the Fresnel reflection principle, don't include any vegetation parameters), it is more suitable for near Lambertian surface, such as Gobi, desert, Lunar and reference panel. Results also showed that the new model could also maintain a high accuracy and stability in sparse observation, which is very important for the retrieval requirements of daily updating BRDF remote sensing products.

  20. Mouse models for gastric cancer: Matching models to biological questions

    Poh, Ashleigh R; O'Donoghue, Robert J J

    2016-01-01

    Abstract Gastric cancer is the third leading cause of cancer‐related mortality worldwide. This is in part due to the asymptomatic nature of the disease, which often results in late‐stage diagnosis, at which point there are limited treatment options. Even when treated successfully, gastric cancer patients have a high risk of tumor recurrence and acquired drug resistance. It is vital to gain a better understanding of the molecular mechanisms underlying gastric cancer pathogenesis to facilitate the design of new‐targeted therapies that may improve patient survival. A number of chemically and genetically engineered mouse models of gastric cancer have provided significant insight into the contribution of genetic and environmental factors to disease onset and progression. This review outlines the strengths and limitations of current mouse models of gastric cancer and their relevance to the pre‐clinical development of new therapeutics. PMID:26809278

  1. Context Sensitive Modeling of Cancer Drug Sensitivity.

    Bo-Juen Chen

    Full Text Available Recent screening of drug sensitivity in large panels of cancer cell lines provides a valuable resource towards developing algorithms that predict drug response. Since more samples provide increased statistical power, most approaches to prediction of drug sensitivity pool multiple cancer types together without distinction. However, pan-cancer results can be misleading due to the confounding effects of tissues or cancer subtypes. On the other hand, independent analysis for each cancer-type is hampered by small sample size. To balance this trade-off, we present CHER (Contextual Heterogeneity Enabled Regression, an algorithm that builds predictive models for drug sensitivity by selecting predictive genomic features and deciding which ones should-and should not-be shared across different cancers, tissues and drugs. CHER provides significantly more accurate models of drug sensitivity than comparable elastic-net-based models. Moreover, CHER provides better insight into the underlying biological processes by finding a sparse set of shared and type-specific genomic features.

  2. Chemical kinetic mechanistic models to investigate cancer biology and impact cancer medicine

    Stites, Edward C

    2013-01-01

    Traditional experimental biology has provided a mechanistic understanding of cancer in which the malignancy develops through the acquisition of mutations that disrupt cellular processes. Several drugs developed to target such mutations have now demonstrated clinical value. These advances are unequivocal testaments to the value of traditional cellular and molecular biology. However, several features of cancer may limit the pace of progress that can be made with established experimental approaches alone. The mutated genes (and resultant mutant proteins) function within large biochemical networks. Biochemical networks typically have a large number of component molecules and are characterized by a large number of quantitative properties. Responses to a stimulus or perturbation are typically nonlinear and can display qualitative changes that depend upon the specific values of variable system properties. Features such as these can complicate the interpretation of experimental data and the formulation of logical hypotheses that drive further research. Mathematical models based upon the molecular reactions that define these networks combined with computational studies have the potential to deal with these obstacles and to enable currently available information to be more completely utilized. Many of the pressing problems in cancer biology and cancer medicine may benefit from a mathematical treatment. As work in this area advances, one can envision a future where such models may meaningfully contribute to the clinical management of cancer patients. (paper)

  3. The establishment of insulin resistance model in FL83B and L6 cell

    Liu, Lanlan; Han, Jizhong; Li, Haoran; Liu, Mengmeng; Zeng, Bin

    2017-10-01

    The insulin resistance models of mouse liver epithelial and rat myoblasts cells were induced by three kinds of inducers: dexamethasone, high insulin and high glucose. The purpose is to select the optimal insulin resistance model, to provide a simple and reliable TR cell model for the study of the pathogenesis of TR and the improvement of TR drugs and functional foods. The MTT method is used for toxicity screening of three compounds, selecting security and suitable concentration. We performed a Glucose oxidase peroxidase (GOD-POD) method involving FL83B and L6 cell with dexamethasone, high insulin and high glucose-induced insulin resistance. Results suggested that FL83B cells with dexamethasone-induced (0.25uM) were established insulin resistance and L6 cells with high-glucose (30mM) and dexamethasone-induced (0.25uM) were established insulin resistance.

  4. Establishment of a new model for culturing rabbit osteoblasts in vitro

    Cao Xianying; Yin Meizhen; Zhang Lina; Li Shipu; Cao Yang

    2006-01-01

    To establish an experimental model for culturing rabbit osteoblasts in vitro, the osteoblasts were isolated from the calvarial bone of a 15-day old rabbit using a method of culturing the bone pieces in a medium after they had been digested by an enzyme for 15 min. The acquired cells were assayed by cell morphology, alkaline phosphatase activity and production of a mineralized matrix. The results showed that the cells had the morphologic characteristics and some biological behaviours of osteoblasts. Based on the primary isolation of osteoblasts from bone and combining digestion with explants, a novel model for culturing rabbit osteoblasts in vitro was established, which is easy, efficient and effective. This model can be used in many studies of osteogenesis mechanisms and bone replacement materials. (communication)

  5. Establishment of SHG-44 human glioma model in brain of wistar rat with stereotactic technique

    Hong Xinyu; Luo Yi'nan; Fu Shuanglin; Wang Zhanfeng; Bie Li; Cui Jiale

    2004-01-01

    Objective: To establish solid intracerebral human glioma model in Wistar rat with xenograft methods. Methods: The SHG-44 cells were injected into brain right caudate nucleus of previous immuno-inhibitory Wistar rats with stereotactic technique. The MRI scans were performed at 1 week and 2 weeks later after implantation. After 2 weeks the rats were killed and pathological examination and immunohistologic stain for human GFAP were used. Results: The MRI scan after 1 week of implantation showed the glioma was growing, pathological histochemical examination demonstrated the tumor was glioma. Human GFAP stain was positive. The growth rate of glioma model was about 60%. Conclusion: Solid intracerebral human glioma model in previous immuno-inhibitory Wistar rat is successfully established

  6. Development of model pump for establishing hydraulic design of primary sodium pumps in PFBR

    Chougule, R.J.; Sahasrabudhe, H.G.; Rao, A.S.L.K.; Balchander, K.; Kale, R.D.

    1994-01-01

    Indira Gandhi Centre for Atomic Research, Kalpakkam indicated requirement of indigenous development of primary sodium pump, handling liquid sodium as coolant in Fast Breeder Reactor. The primary sodium pump concept selected in its preliminary design is a vertical, single stage, with single suction impeller, suction facing downwards. The pump is having diffuser, discharge casing and discharge collector. The 1/3 rd size model pump is developed to establish the hydraulic performance of the prototype primary sodium pump. The main objectives were to verify the hydraulic design to operate on low net positive suction head available (NPSHA), no evidence of visible cavitation at available NPSHA, the pump should be designed with a diffuser etc. The model pump PSP 250/40 was designed and successfully developed by Research and Development Division of M/s Kirloskar Brothers Ltd., Kirloskarvadi. The performance testing using model pump was successfully carried out on a closed circuit test rig. The performance of a model pump at three different speeds 1900 rpm, 1456 rpm and 975 rpm was established. The values of hydraulic axial thrust with and without balancing holes on impeller at 1900 rpm was measured. Visual cavitation study at 1900 rpm was carried out to establish the NPSH at bubble free operation of the pump. The tested performance of the model pump is converted to the full scale prototype pump. The predicted performance of prototype pump at 700 rpm was found to be meeting fully with the expected duties. (author). 6 figs., 3 tabs

  7. Branching process models of cancer

    Durrett, Richard

    2015-01-01

    This volume develops results on continuous time branching processes and applies them to study rate of tumor growth, extending classic work on the Luria-Delbruck distribution. As a consequence, the authors calculate the probability that mutations that confer resistance to treatment are present at detection and quantify the extent of tumor heterogeneity. As applications, the authors evaluate ovarian cancer screening strategies and give rigorous proofs for results of Heano and Michor concerning tumor metastasis. These notes should be accessible to students who are familiar with Poisson processes and continuous time. Richard Durrett is mathematics professor at Duke University, USA. He is the author of 8 books, over 200 journal articles, and has supervised more than 40 Ph.D. students. Most of his current research concerns the applications of probability to biology: ecology, genetics, and most recently cancer.

  8. Learning while (re)configuring: Business model innovation processes in established firms

    Berends, Hans; Smits, Armand; Reymen, Isabelle; Podoynitsyna, Ksenia

    2016-01-01

    This study addresses the question of how established organizations develop new business models over time, using a process research approach to trace how four business model innovation trajectories unfold. With organizational learning as analytical lens, we discern two process patterns: “drifting” starts with an emphasis on experiential learning and shifts later to cognitive search; “leaping,” in contrast, starts with an emphasis on cognitive search and shifts later to experiential learning. Both drifting and leaping can result in radical business model innovations, while their occurrence depends on whether a new business model takes off from an existing model and when it goes into operation. We discuss the implications of these findings for theory on business models and organizational learning. PMID:28596704

  9. Learning while (re)configuring: Business model innovation processes in established firms.

    Berends, Hans; Smits, Armand; Reymen, Isabelle; Podoynitsyna, Ksenia

    2016-08-01

    This study addresses the question of how established organizations develop new business models over time, using a process research approach to trace how four business model innovation trajectories unfold. With organizational learning as analytical lens, we discern two process patterns: "drifting" starts with an emphasis on experiential learning and shifts later to cognitive search; "leaping," in contrast, starts with an emphasis on cognitive search and shifts later to experiential learning. Both drifting and leaping can result in radical business model innovations, while their occurrence depends on whether a new business model takes off from an existing model and when it goes into operation. We discuss the implications of these findings for theory on business models and organizational learning.

  10. Emerging and established global life-style risk factors for cancer of the upper aero-digestive tract.

    Gupta, Bhawna; Johnson, Newell W

    2014-01-01

    Upper aero-digestive tract cancer is a multidimensional problem, international trends showing complex rises and falls in incidence and mortality across the globe, with variation across different cultural and socio-economic groups. This paper seeks some explanations and identifies some research and policy needs. The literature illustrates the multifactorial nature of carcinogenesis. At the cellular level, it is viewed as a multistep process involving multiple mutations and selection for cells with progressively increasing capacity for proliferation, survival, invasion, and metastasis. Established and emerging risk factors, in addition to changes in incidence and prevalence of cancers of the upper aero-digestive tract, were identified. Exposure to tobacco and alcohol, as well as diets inadequate in fresh fruits and vegetables, remain the major risk factors, with persistent infection by particular so-called "high risk" genotypes of human papillomavirus increasingly recognised as also playing an important role in a subset of cases, particularly for the oropharynx. Chronic trauma to oral mucosa from poor restorations and prostheses, in addition to poor oral hygiene with a consequent heavy microbial load in the mouth, are also emerging as significant risk factors. Understanding and quantifying the impact of individual risk factors for these cancers is vital for health decision-making, planning and prevention. National policies and programmes should be designed and implemented to control exposure to environmental risks, by legislation if necessary, and to raise awareness so that people are provided with the information and support they need to adopt healthy lifestyles.

  11. Establishment of mouse neuron and microglial cell co-cultured models and its action mechanism.

    Zhang, Bo; Yang, Yunfeng; Tang, Jun; Tao, Yihao; Jiang, Bing; Chen, Zhi; Feng, Hua; Yang, Liming; Zhu, Gang

    2017-06-27

    The objective of this study is to establish a co-culture model of mouse neurons and microglial cells, and to analyze the mechanism of action of oxygen glucose deprivation (OGD) and transient oxygen glucose deprivation (tOGD) preconditioning cell models. Mouse primary neurons and BV2 microglial cells were successfully cultured, and the OGD and tOGD models were also established. In the co-culture of mouse primary neurons and microglial cells, the cell number of tOGD mouse neurons and microglial cells was larger than the OGD cell number, observed by a microscope. CCK-8 assay result showed that at 1h after treatment, the OD value in the control group is lower compared to all the other three groups (P control group compared to other three groups (P neurons cells were cultured. In the meantime mouse BV2 microglia cells were cultured. Two types of cells were co-cultured, and OGD and tOGD cell models were established. There were four groups in the experiment: control group (OGD), treatment group (tOGD+OGD), placebo group (tOGD+OGD+saline) and minocycline intervention group (tOGD+OGD+minocycline). CCK-8 kit was used to detect cell viability and flow cytometry was used to detect apoptosis. In this study, mouse primary neurons and microglial cells were co-cultured. The OGD and tOGD models were established successfully. tOGD was able to effectively protect neurons and microglial cells from damage, and inhibit the apoptosis caused by oxygen glucose deprivation.

  12. Modeling mechanical interactions between cancerous mammary acini

    Wang, Jeffrey; Liphardt, Jan; Rycroft, Chris

    2015-03-01

    The rules and mechanical forces governing cell motility and interactions with the extracellular matrix of a tissue are often critical for understanding the mechanisms by which breast cancer is able to spread through the breast tissue and eventually metastasize. Ex vivo experimentation has demonstrated the the formation of long collagen fibers through collagen gels between the cancerous mammary acini responsible for milk production, providing a fiber scaffolding along which cancer cells can disorganize. We present a minimal mechanical model that serves as a potential explanation for the formation of these collagen fibers and the resultant motion. Our working hypothesis is that cancerous cells induce this fiber formation by pulling on the gel and taking advantage of the specific mechanical properties of collagen. To model this system, we employ a new Eulerian, fixed grid simulation method to model the collagen as a nonlinear viscoelastic material subject to various forces coupled with a multi-agent model to describe individual cancer cells. We find that these phenomena can be explained two simple ideas: cells pull collagen radially inwards and move towards the tension gradient of the collagen gel, while being exposed to standard adhesive and collision forces.

  13. Next-generation sequence analysis of cancer xenograft models.

    Fernando J Rossello

    Full Text Available Next-generation sequencing (NGS studies in cancer are limited by the amount, quality and purity of tissue samples. In this situation, primary xenografts have proven useful preclinical models. However, the presence of mouse-derived stromal cells represents a technical challenge to their use in NGS studies. We examined this problem in an established primary xenograft model of small cell lung cancer (SCLC, a malignancy often diagnosed from small biopsy or needle aspirate samples. Using an in silico strategy that assign reads according to species-of-origin, we prospectively compared NGS data from primary xenograft models with matched cell lines and with published datasets. We show here that low-coverage whole-genome analysis demonstrated remarkable concordance between published genome data and internal controls, despite the presence of mouse genomic DNA. Exome capture sequencing revealed that this enrichment procedure was highly species-specific, with less than 4% of reads aligning to the mouse genome. Human-specific expression profiling with RNA-Seq replicated array-based gene expression experiments, whereas mouse-specific transcript profiles correlated with published datasets from human cancer stroma. We conclude that primary xenografts represent a useful platform for complex NGS analysis in cancer research for tumours with limited sample resources, or those with prominent stromal cell populations.

  14. Business models and opportunities for cancer vaccine developers.

    Kudrin, Alex

    2012-10-01

    Despite of growing oncology pipeline, cancer vaccines contribute only to a minor share of total oncology-attributed revenues. This is mainly because of a limited number of approved products and limited sales from products approved under compassionate or via early access entry in smaller and less developed markets. However revenue contribution from these products is extremely limited and it remains to be established whether developers are breaking even or achieving profitability with existing sales. Cancer vaccine field is well recognized for high development costs and risks, low historical rates of investment return and high probability of failures arising in ventures, partnerships and alliances. The cost of reimbursement for new oncology agents is not universally acceptable to payers limiting the potential for a global expansion, market access and reducing probability of commercial success. In addition, the innovation in cancer immunotherapy is currently focused in small and mid-size biotech companies and academic institutions struggling for investment. Existing R&D innovation models are deemed unsustainable in current "value-for-money" oriented healthcare environment. New business models should be much more open to collaborative, networked and federated styles, which could help to outreach global, markets and increase cost-efficiencies across an entire value chain. Lessons learned from some developing countries and especially from South Korea illustrate that further growth of cancer vaccine industry will depends not only on new business models but also will heavily rely on regional support and initiatives from different bodies, such as governments, payers and regulatory bodies.

  15. Mouse Models for Studying Oral Cancer: Impact in the Era of Cancer Immunotherapy.

    Luo, J J; Young, C D; Zhou, H M; Wang, X J

    2018-04-01

    Model systems for oral cancer research have progressed from tumor epithelial cell cultures to in vivo systems that mimic oral cancer genetics, pathological characteristics, and tumor-stroma interactions of oral cancer patients. In the era of cancer immunotherapy, it is imperative to use model systems to test oral cancer prevention and therapeutic interventions in the presence of an immune system and to discover mechanisms of stromal contributions to oral cancer carcinogenesis. Here, we review in vivo mouse model systems commonly used for studying oral cancer and discuss the impact these models are having in advancing basic mechanisms, chemoprevention, and therapeutic intervention of oral cancer while highlighting recent discoveries concerning the role of immune cells in oral cancer. Improvements to in vivo model systems that highly recapitulate human oral cancer hold the key to identifying features of oral cancer initiation, progression, and invasion as well as molecular and cellular targets for prevention, therapeutic response, and immunotherapy development.

  16. Model Checking of a Diabetes-Cancer Model

    Gong, Haijun; Zuliani, Paolo; Clarke, Edmund M.

    2011-06-01

    Accumulating evidence suggests that cancer incidence might be associated with diabetes mellitus, especially Type II diabetes which is characterized by hyperinsulinaemia, hyperglycaemia, obesity, and overexpression of multiple WNT pathway components. These diabetes risk factors can activate a number of signaling pathways that are important in the development of different cancers. To systematically understand the signaling components that link diabetes and cancer risk, we have constructed a single-cell, Boolean network model by integrating the signaling pathways that are influenced by these risk factors to study insulin resistance, cancer cell proliferation and apoptosis. Then, we introduce and apply the Symbolic Model Verifier (SMV), a formal verification tool, to qualitatively study some temporal logic properties of our diabetes-cancer model. The verification results show that the diabetes risk factors might not increase cancer risk in normal cells, but they will promote cell proliferation if the cell is in a precancerous or cancerous stage characterized by losses of the tumor-suppressor proteins ARF and INK4a.

  17. A Behavioral Maturity Model to Establish Knowledge Management in an Organization

    C. S. Fashami

    2017-06-01

    Full Text Available Modern organizations need intangible assets such as organizational knowledge and human resources to gain competitive advantage in the market. Organizations can provide opportunities for behavioral maturity of managers to establish knowledge management. This study tries to develop a behavioral maturity model for managements to examine effectiveness of knowledge management. The study is conducted in Iran Insurance Company as an empirical case study. Twenty academic and organizational experts are selected for the study. Employees and managers of Iran Insurance Company are used to measure and test conceptual model (behavioral maturity of managers to establish knowledge management. Both interview and questionnaire tools are used to collect data. Fuzzy AHP and PLS methods are used to analyze the collected data. Fuzzy AHP results show that transformational leadership, human and social skills, knowledge orientation, emotional intelligence, trustful climate are identified as highly effective priorities.

  18. Establishment of an animal model of mice with radiation- injured soft tissue blood vessels

    Wang Daiyou; Yu Dahai; Wu Jiaxiao; Wei Shanliang; Wen Yuming

    2004-01-01

    Objective: The aim of this study was to establish an animal model of mice with radiation-injured soft tissue blood vessels. Methods: Forty male mice were irradiated with 30 Gy on the right leg. After the irradiation was finished each of the 40 male mice was tested with angiography, and its muscle tissues on the bilateral legs were examined with vessel staining assay and electron microscopy. Results: The results showed that the number of vessels on the right leg was less than that on the left leg, the microvessel density, average diameter and average sectional area of the right leg were all lower than those of the left, and the configuration and ultra-structure of vessels were also different between both sides of legs. Conclusion: In the study authors successfully established an animal model of mice with radiation-injured soft tissue blood vessels

  19. Establishment and Characterization of a Tumor Stem Cell-Based Glioblastoma Invasion Model

    Jensen, Stine Skov; Meyer, Morten; Petterson, Stine Asferg

    2016-01-01

    AIMS: Glioblastoma is the most frequent and malignant brain tumor. Recurrence is inevitable and most likely connected to tumor invasion and presence of therapy resistant stem-like tumor cells. The aim was therefore to establish and characterize a three-dimensional in vivo-like in vitro model taking...... invasion and tumor stemness into account. METHODS: Glioblastoma stem cell-like containing spheroid (GSS) cultures derived from three different patients were established and characterized. The spheroids were implanted in vitro into rat brain slice cultures grown in stem cell medium and in vivo into brains...... of immuno-compromised mice. Invasion was followed in the slice cultures by confocal time-lapse microscopy. Using immunohistochemistry, we compared tumor cell invasion as well as expression of proliferation and stem cell markers between the models. RESULTS: We observed a pronounced invasion into brain slice...

  20. Multiscale agent-based cancer modeling.

    Zhang, Le; Wang, Zhihui; Sagotsky, Jonathan A; Deisboeck, Thomas S

    2009-04-01

    Agent-based modeling (ABM) is an in silico technique that is being used in a variety of research areas such as in social sciences, economics and increasingly in biomedicine as an interdisciplinary tool to study the dynamics of complex systems. Here, we describe its applicability to integrative tumor biology research by introducing a multi-scale tumor modeling platform that understands brain cancer as a complex dynamic biosystem. We summarize significant findings of this work, and discuss both challenges and future directions for ABM in the field of cancer research.

  1. The Internet addiction components model and personality: establishing construct validity via a nomological network

    Kuss, DJ; Shorter, GW; Van Rooij, AJ; Van de Mheen, D; Griffiths, MD

    2014-01-01

    There is growing concern over excessive and sometimes problematic Internet use. Drawing upon the framework of the components model of addiction (Griffiths, 2005), Internet addiction appears as behavioural addiction characterised by the following symptoms: salience, withdrawal, tolerance, mood modification, relapse and conflict. A number of factors have been associated with an increased risk for Internet addiction, including personality traits. The overall aim of this study was to establish th...

  2. A Behavioral Maturity Model to Establish Knowledge Management in an Organization

    Fashami, C. S.; Babaei, M.

    2017-01-01

    Modern organizations need intangible assets such as organizational knowledge and human resources to gain competitive advantage in the market. Organizations can provide opportunities for behavioral maturity of managers to establish knowledge management. This study tries to develop a behavioral maturity model for managements to examine effectiveness of knowledge management. The study is conducted in Iran Insurance Company as an empirical case study. Twenty academic and organizational experts ar...

  3. 1993-1994 Final technical report for establishing the SECME Model in the District of Columbia

    Vickers, R.G.

    1995-12-31

    This is the final report for a program to establish the SECME Model in the District of Columbia. This program has seen the development of a partnership between the District of Columbia Public Schools, the University of the District of Columbia, the Department of Energy, and SECME. This partnership has demonstrated positive achievement in mathematics and science education and learning in students within the District of Columbia.

  4. 1993-1994 Final technical report for establishing the SECME Model in the District of Columbia

    Vickers, R.G.

    1995-01-01

    This is the final report for a program to establish the SECME Model in the District of Columbia. This program has seen the development of a partnership between the District of Columbia Public Schools, the University of the District of Columbia, the Department of Energy, and SECME. This partnership has demonstrated positive achievement in mathematics and science education and learning in students within the District of Columbia

  5. Establishment of Grain Farmers' Supply Response Model and Empirical Analysis under Minimum Grain Purchase Price Policy

    Zhang, Shuang

    2012-01-01

    Based on farmers' supply behavior theory and price expectations theory, this paper establishes grain farmers' supply response model of two major grain varieties (early indica rice and mixed wheat) in the major producing areas, to test whether the minimum grain purchase price policy can have price-oriented effect on grain production and supply in the major producing areas. Empirical analysis shows that the minimum purchase price published annually by the government has significant positive imp...

  6. Establishment of a large panel of patient-derived preclinical models of human renal cell carcinoma

    Lang, Herv?; B?raud, Claire; Bethry, Audrey; Danilin, Sabrina; Lindner, V?ronique; Coquard, Catherine; Rothhut, Sylvie; Massfelder, Thierry

    2016-01-01

    The objective of the present work was to establish a large panel of preclinical models of human renal cell carcinoma (RCC) directly from patients, faithfully reproducing the biological features of the original tumor. RCC tissues (all stages/subtypes) were collected for 8 years from 336 patients undergoing surgery, xenografted subcutaneously in nude mice, and serially passaged into new mice up to 13 passages. Tissue samples from the primary tumor and tumors grown in mice through passages were ...

  7. Establishing credibility in the environmental models used for safety and licensing calculations in the nuclear industry

    Davis, P.A.

    1997-01-01

    Models that simulate the transport and behaviour of radionuclides in the environment are used extensively in the nuclear industry for safety and licensing purposes. They are needed to calculate derived release limits for new and operating facilities, to estimate consequences following hypothetical accidents and to help manage a real emergency. But predictions generated for these purposes are essentially meaningless unless they are accompanied by a quantitative estimate of the confidence that can be placed in them. For example, in an emergency where there has been an accidental release of radioactivity to the atmosphere, decisions based on a validated model with small uncertainties would likely be very different from those based on an untested model, or on one with large uncertainties. This paper begins with a discussion of some general methods for establishing the credibility of model predictions. The focus will be on environmental transport models but the principles apply to models of all kinds. Establishing the credibility of a model is not a trivial task, It involves a number of tasks including face validation, verification, experimental validation and sensitivity and uncertainty analyses. The remainder of the paper will present quantitative results relating to the credibility of environmental transport models. Model formation, choice of parameter values and the influence of the user will all be discussed as sources of uncertainty in predictions. The magnitude of uncertainties that must be expected in various applications of the models will be presented. The examples used throughout the paper are drawn largely from recent work carried out in BIOMOVS and VAMP. (DM)

  8. Assessing the potential for establishment of western cherry fruit fly using ecological niche modeling.

    Kumar, Sunil; Neven, Lisa G; Yee, Wee L

    2014-06-01

    Sweet cherries, Prunus avium (L.) L., grown in the western United States are exported to many countries around the world. Some of these countries have enforced strict quarantine rules and trade restrictions owing to concerns about the potential establishment and subsequent spread of western cherry fruit fly, Rhagoletis indifferens Curran (Diptera: Tephritidae), a major quarantine pest of sweet cherry. We used 1) niche models (CLIMEX and MaxEnt) to map the climatic suitability, 2) North Carolina State University-Animal and Plant Health Inspection Service Plant Pest Forecasting System to examine chilling requirement, and 3) host distribution and availability to assess the potential for establishment of R. indifferens in areas of western North America where it currently does not exist and eight current or potential fresh sweet cherry markets: Colombia, India, Indonesia, Malaysia, Taiwan, Thailand, Venezuela, and Vietnam. Results from niche models conformed well to the current distribution of R. indifferens in western North America. MaxEnt and CLIMEX models had high performance and predicted climatic suitability in some of the countries (e.g., Andean range in Colombia and Venezuela, northern and northeastern India, central Taiwan, and parts of Vietnam). However, our results showed no potential for establishment of R. indifferens in Colombia, Indonesia, Malaysia, Taiwan, Thailand, Venezuela, and Vietnam when the optimal chilling requirement to break diapause (minimum temperature policy makers.

  9. A rabbit model of fatal hypothyroidism mimicking "myxedema coma" established by microscopic total thyroidectomy.

    Ono, Yosuke; Fujita, Masanori; Ono, Sachiko; Ogata, Sho; Tachibana, Shoichi; Tanaka, Yuji

    2016-06-30

    Myxedema coma (MC) is a life-threatening endocrine crisis caused by severe hypothyroidism. However, validated diagnostic criteria and treatment guidelines for MC have not been established owing to its rarity. Therefore, a valid animal model is required to investigate the pathologic and therapeutic aspects of MC. The aim of the present study was to establish an animal model of MC induced by total thyroidectomy. We utilized 14 male New Zealand White rabbits anesthetized via intramuscular ketamine and xylazine administration. A total of 7 rabbits were completely thyroidectomized under a surgical microscope (thyroidectomized group) and the remainder underwent sham operations (control group). The animals in both groups were monitored without thyroid hormone replacement for 15 weeks. Pulse rate, blood pressure, body temperature, and electrocardiograms (ECG) were recorded and blood samples were taken from the jugular vein immediately prior to the thyroidectomy and 2 and 4 weeks after surgery. The thyroidectomized rabbits showed a marked reduction of serum thyroxine levels at 4 weeks after the surgical procedure vs. controls (0.50±0.10 vs. 3.32±0.68 μg/dL, pmyxedema heart. In summary, we have established a rabbit model of fatal hypothyroidism mimicking MC, which may facilitate pathophysiological and molecular investigations of MC and evaluations of new therapeutic interventions.

  10. Establishment and Characterization of a Tumor Stem Cell-Based Glioblastoma Invasion Model.

    Stine Skov Jensen

    Full Text Available Glioblastoma is the most frequent and malignant brain tumor. Recurrence is inevitable and most likely connected to tumor invasion and presence of therapy resistant stem-like tumor cells. The aim was therefore to establish and characterize a three-dimensional in vivo-like in vitro model taking invasion and tumor stemness into account.Glioblastoma stem cell-like containing spheroid (GSS cultures derived from three different patients were established and characterized. The spheroids were implanted in vitro into rat brain slice cultures grown in stem cell medium and in vivo into brains of immuno-compromised mice. Invasion was followed in the slice cultures by confocal time-lapse microscopy. Using immunohistochemistry, we compared tumor cell invasion as well as expression of proliferation and stem cell markers between the models.We observed a pronounced invasion into brain slice cultures both by confocal time-lapse microscopy and immunohistochemistry. This invasion closely resembled the invasion in vivo. The Ki-67 proliferation indexes in spheroids implanted into brain slices were lower than in free-floating spheroids. The expression of stem cell markers varied between free-floating spheroids, spheroids implanted into brain slices and tumors in vivo.The established invasion model kept in stem cell medium closely mimics tumor cell invasion into the brain in vivo preserving also to some extent the expression of stem cell markers. The model is feasible and robust and we suggest the model as an in vivo-like model with a great potential in glioma studies and drug discovery.

  11. Establishment of a bioassay system for cancer risk assessment in energy technology

    Ts' o, P.O.P.; Bruce, S.A.; Brown, A. (eds.)

    1983-09-01

    Separate abstracts were prepared for 20 papers in this report. For several years the Department of Energy (DOE), Office of Health and Environmental Research (OHER), has supported a research program aimed at developing new experimental approaches for the improvement of cancer risk assessments. The central issue is to overcome the organizational, species and other barriers that make it difficult to extrapolate laboratory-based data to predict risk to man. Most of the participants at the meeting are involved in research aimed at understanding the mechanism(s) of chemical carcinogenesis. Complex mixtures of chemicals are associated with many energy technologies. DOE's initial program emphasis focused on semi-applied research aimed at quantitative evaluation of carcinogenic activity of complex materials. Since much progress has been made in DOE integrated technology-specific chemical-biological characterization studies, the number and kinds of chemicals of concern has been reduced to a relatively few well-defined classes. Although the classes of compounds seem to be unique to some of the synfuel technologies, they are quite similar to compounds of general interest, for example, poly-nuclear aromatic hydrocarbons. Special emphasis was placed on molecular and cellular dosimetry as one of the key requirements for quantitative comparison of effects at the cell level in vivo and in vitro. Although it is relatively easy to measure cell, tissue, organ and whole organism doses associated with radiation exposures, we are just learning how to do this for chemical agents. Several methods have been developed in the past several years which can be used.

  12. Human breast cancer histoid: an in vitro 3-dimensional co-culture model that mimics breast cancer tissue.

    Kaur, Pavinder; Ward, Brenda; Saha, Baisakhi; Young, Lillian; Groshen, Susan; Techy, Geza; Lu, Yani; Atkinson, Roscoe; Taylor, Clive R; Ingram, Marylou; Imam, S Ashraf

    2011-12-01

    Progress in our understanding of heterotypic cellular interaction in the tumor microenvironment, which is recognized to play major roles in cancer progression, has been hampered due to unavailability of an appropriate in vitro co-culture model. The aim of this study was to generate an in vitro 3-dimensional human breast cancer model, which consists of cancer cells and fibroblasts. Breast cancer cells (UACC-893) and fibroblasts at various densities were co-cultured in a rotating suspension culture system to establish co-culture parameters. Subsequently, UACC-893, BT.20, or MDA.MB.453 were co-cultured with fibroblasts for 9 days. Co-cultures resulted in the generation of breast cancer histoid (BCH) with cancer cells showing the invasion of fibroblast spheroids, which were visualized by immunohistochemical (IHC) staining of sections (4 µm thick) of BCH. A reproducible quantitative expression of C-erbB.2 was detected in UACC-893 cancer cells in BCH sections by IHC staining and the Automated Cellular Imaging System. BCH sections also consistently exhibited qualitative expression of pancytokeratins, p53, Ki-67, or E-cadherin in cancer cells and that of vimentin or GSTPi in fibroblasts, fibronectin in the basement membrane and collagen IV in the extracellular matrix. The expression of the protein analytes and cellular architecture of BCH were markedly similar to those of breast cancer tissue.

  13. Proteomics of a new esophageal cancer cell line established from Persian patient.

    Moghanibashi, Mehdi; Jazii, Ferdous Rastgar; Soheili, Zahra-Soheila; Zare, Maryam; Karkhane, Aliasghar; Parivar, Kazem; Mohamadynejad, Parisa

    2012-05-25

    Although the highest incidence of esophageal squamous cell carcinoma (ESCC) has repeatedly been reported from Persia (Iran), nevertheless the so far proteomic published reports were limited to one study on tissue specimens. Here we report the proteome of a newly established cell line from Persian ESCC patients and compare it with the normal primary cell proteome. Among polypeptides, whose expression was different in cell line sixteen polypeptides were identified by MALDI/TOF/TOF spectrometry. S100-A8 protein, annexin A1, annexin A2, regulatory subunit of calpain, subunit alpha type-3 of proteasome and glutamate dehydrogenase 1 were proteins down-regulated in cell line while peroxiredoxin-5, non-muscle myosin light polypeptide 6, keratin 1, annexin A4, keratin 8, tropomyosin 3, stress-induced-phosphoprotein 1 and albumin were found to be subject of up-regulation in cell line compared to the primary normal cells. The proteomic results were further verified by western blotting and RT-PCR on annexin A1 and keratin 8. In addition, among the aforementioned proteins, glutamate dehydrogenase 1, regulatory subunit of calpain, subunit alpha of type-3 proteasome and annexin A4 are proteins whose deregulation in ESCC is reported for the first time by this study. Copyright © 2012 Elsevier B.V. All rights reserved.

  14. Establishment of a Model of Microencapsulated SGC7901 Human Gastric Carcinoma Cells Cocultured with Tumor-Associated Macrophages

    Jin-Ming Zhu

    2018-01-01

    Full Text Available The important factors of poor survival of gastric cancer (GC are relapse and metastasis. For further elucidation of the mechanism, a culture system mimicking the microenvironment of the tumor in humans was needed. We established a model of microencapsulated SGC7901 human GC cells and evaluated the effects of coculturing spheres with tumor-associated macrophages (TAMs. SGC7901 cells were encapsulated in alginate-polylysine-sodium alginate (APA microcapsules using an electrostatic droplet generator. MTT assays showed that the numbers of microencapsulated cells were the highest after culturing for 14 days. Metabolic curves showed consumption of glucose and production of lactic acid by day 20. Immunocytochemistry confirmed that Proliferating Cell Nuclear Antigen (PCNA and Vascular Endothelial Growth Factor (VEGF were expressed in microencapsulated SGC7901 cells on days 7 and 14. The expression of PCNA was observed outside spheroids; however, VEGF was found in the entire spheroids. PCNA and VEGF were increased after being cocultured with TAMs. Matrix metalloproteinase-2 (MMP-2 and matrix metalloproteinase-9 (MMP-9 expressions were detected in the supernatant of microencapsulated cells cocultured with TAMs but not in microencapsulated cells. Our study confirms the successful establishment of the microencapsulated GC cells. TAMs can promote PCNA, VEGF, MMP-2, and MMP-9 expressions of the GC cells.

  15. Establishment and correction of an Echelle cross-prism spectrogram reduction model

    Zhang, Rui; Bayanheshig; Li, Xiaotian; Cui, Jicheng

    2017-11-01

    The accuracy of an echelle cross-prism spectrometer depends on the matching degree between the spectrum reduction model and the actual state of the spectrometer. However, the error of adjustment can change the actual state of the spectrometer and result in a reduction model that does not match. This produces an inaccurate wavelength calibration. Therefore, the calibration of a spectrogram reduction model is important for the analysis of any echelle cross-prism spectrometer. In this study, the spectrogram reduction model of an echelle cross-prism spectrometer was established. The image position laws of a spectrometer that varies with the system parameters were simulated to the influence of the changes in prism refractive index, focal length and so on, on the calculation results. The model was divided into different wavebands. The iterative method, least squares principle and element lamps with known characteristic wavelength were used to calibrate the spectral model in different wavebands to obtain the actual values of the system parameters. After correction, the deviation of actual x- and y-coordinates and the coordinates calculated by the model are less than one pixel. The model corrected by this method thus reflects the system parameters in the current spectrometer state and can assist in accurate wavelength extraction. The instrument installation and adjustment would be guided in model-repeated correction, reducing difficulty of equipment, respectively.

  16. A modeling approach to establish environmental flow threshold in ungauged semidiurnal tidal river

    Akter, A.; Tanim, A. H.

    2018-03-01

    Due to shortage of flow monitoring data in ungauged semidiurnal river, 'environmental flow' (EF) determination based on its key component 'minimum low flow' is always difficult. For EF assessment this study selected a reach immediately after the Halda-Karnafuli confluence, a unique breeding ground for Indian Carp fishes of Bangladesh. As part of an ungauged tidal river, EF threshold establishment faces challenges in changing ecological paradigms with periodic change of tides and hydrologic alterations. This study describes a novel approach through modeling framework comprising hydrological, hydrodynamic and habitat simulation model. The EF establishment was conceptualized according to the hydrologic process of an ungauged semi-diurnal tidal regime in four steps. Initially, a hydrologic model coupled with a hydrodynamic model to simulate flow considering land use changes effect on streamflow, seepage loss of channel, friction dominated tidal decay as well as lack of long term flow characteristics. Secondly, to define hydraulic habitat feature, a statistical analysis on derived flow data was performed to identify 'habitat suitability'. Thirdly, to observe the ecological habitat behavior based on the identified hydrologic alteration, hydraulic habitat features were investigated. Finally, based on the combined habitat suitability index flow alteration and ecological response relationship was established. Then, the obtained EF provides a set of low flow indices of desired regime and thus the obtained discharge against maximum Weighted Usable Area (WUA) was defined as EF threshold for the selected reach. A suitable EF regime condition was obtained within flow range 25-30.1 m3/s i.e., around 10-12% of the mean annual runoff of 245 m3/s and these findings are within researchers' recommendation of minimum flow requirement. Additionally it was observed that tidal characteristics are dominant process in semi-diurnal regime. However, during the study period (2010-2015) the

  17. Development and Symbiosis Establishment in the Cnidarian Endosymbiosis Model Aiptasia sp.

    Bucher, Madeline; Wolfowicz, Iliona; Voss, Philipp A; Hambleton, Elizabeth A; Guse, Annika

    2016-01-25

    Symbiosis between photosynthetic algae and heterotrophic organisms is widespread. One prominent example of high ecological relevance is the endosymbiosis between dinoflagellate algae of the genus Symbiodinium and reef-building corals, which typically acquire symbionts anew each generation during larval stages. The tropical sea anemone Aiptasia sp. is a laboratory model system for this endosymbiosis and, similar to corals, produces non-symbiotic larvae that establish symbiosis by phagocytosing Symbiodinium from the environment into the endoderm. Here we generate the first overview of Aiptasia embryogenesis and larval development and establish in situ hybridization to analyze expression patterns of key early developmental regulators. Next, we quantify morphological changes in developing larvae and find a substantial enlargement of the gastric cavity over time. Symbiont acquisition starts soon after mouth formation and symbionts occupy a major portion of the host cell in which they reside. During the first 14 days of development, infection efficiency remains constant while in contrast, localization of phagocytosed symbionts changes, indicating that the occurrence of functional phagocytosing cells may be developmentally regulated. Taken together, here we provide the essential framework to further develop Aiptasia as a model system for the analysis of symbiosis establishment in cnidarian larvae at the molecular level.

  18. Cancer immunotherapy : insights from transgenic animal models

    McLaughlin, PMJ; Kroesen, BJ; Harmsen, MC; de Leij, LFMH

    2001-01-01

    A wide range of strategies in cancer immunotherapy has been developed in the last decade, some of which are currently being used in clinical settings. The development of these immunotherapeutical strategies has been facilitated by the generation of relevant transgenic animal models. Since the

  19. Modeling bladder cancer in mice: opportunities and challenges

    Kobayashi, Takashi; Owczarek, Tomasz B.; McKiernan, James M.; Abate-Shen, Cory

    2015-01-01

    The prognosis and treatment of bladder cancer have hardly improved in the last 20 years. Bladder cancer remains a debilitating and often fatal disease, and among the most costly cancers to treat. The generation of informative mouse models has the potential to improve our understanding of bladder cancer progression, as well as impact its diagnosis and treatment. However, relatively few mouse models of bladder cancer have been described and particularly few that develop invasive cancer phenotypes. This review focuses on opportunities for improving the landscape of mouse models of bladder cancer. PMID:25533675

  20. A nutritional risk screening model for patients with liver cirrhosis established using discriminant analysis

    ZHU Binghua

    2017-06-01

    Full Text Available ObjectiveTo establish a nutritional risk screening model for patients with liver cirrhosis using discriminant analysis. MethodsThe clinical data of 273 patients with liver cirrhosis who were admitted to Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine from August 2015 to March 2016 were collected. Body height, body weight, upper arm circumference, triceps skinfold thickness, subscapular skinfold thickness, and hand grip strength were measured and recorded, and then body mass index (BMI and upper arm muscle circumference were calculated. Laboratory markers including liver function parameters, renal function parameters, and vitamins were measured. The patients were asked to complete Nutritional Risk Screening 2002 and Malnutrition Universal Screening Tool (MUST, and a self-developed nutritional risk screening pathway was used for nutritional risk classification. Observation scales of the four diagnostic methods in traditional Chinese medicine were used to collect patients′ symptoms and signs. Continuous data were expressed as mean±SD (x±s; an analysis of variance was used for comparison between multiple groups, and the least significant difference t-test was used for further comparison between two groups. Discriminant analysis was used for model establishment, and cross validation was used for model verification. ResultsThe nutritional risk screening pathway for patients with liver cirrhosis was used for the screening of respondents, and there were 49 patients (17.95% in non-risk group, 49 (17.95% in possible-risk group, and 175 (64.10% in risk group. The distance criterion function was used to establish the nutritional risk screening model for patients with liver cirrhosis: D1=-11.885+0.310×BMI+0150×MAC+0.005×P-Alb-0.001×Vit B12+0.103×Vit D-0.89×ascites-0.404×weakness-0.560×hypochondriac pain+0035×dysphoria with feverish sensation (note: if a patient has ascites, weakness, hypochondriac pain

  1. Establishment and validation of the model of molten pool in fast reactor

    Zhou Shufeng; Luo Rui; Wang Zhou; Shi Xiaobo; Yang Xianyong

    2007-01-01

    Running under the beyond design base accidental condition, sodium boiling and dry-out will soon be brought about in LMFBR. If not stopped timely, the fuel pins of the subassembly will be melt and broken to form a molten pool at the bottom of the subassembly. to present a reasonable analysis about the molten pool accident, a method of establishing model according to the mechanism is selected, by which an integral model of the molten pool is established. Validated on the three power groups of BF1 experiments which belong to the France SCARABEE series experimenters, the model shows good results. After compared with the models of GEYSER and BF2 experiments which had been validated before, some conclusions about mechanism of molten pool are derived. Moreover, through comparing the relative parameters such as the discharged heat and the increment of temperature etc., a reasonable analysis about the type of heat transfer is present, on the basis of which some conclusions are derived as well. (authors)

  2. [Establishment of A Clinical Prediction Model of Prolonged Air Leak 
after Anatomic Lung Resection].

    Wu, Xianning; Xu, Shibin; Ke, Li; Fan, Jun; Wang, Jun; Xie, Mingran; Jiang, Xianliang; Xu, Meiqing

    2017-12-20

    Prolonged air leak (PAL) after anatomic lung resection is a common and challenging complication in thoracic surgery. No available clinical prediction model of PAL has been established in China. The aim of this study was to construct a model to identify patients at increased risk of PAL by using preoperative factors exclusively. We retrospectively reviewed clinical data and PAL occurrence of patients after anatomic lung resection, in department of thoracic surgery, Anhui Provincial Hospital Affiliated to Anhui Medical University, from January 2016 to October 2016. 359 patients were in group A, clinical data including age, body mass index (BMI), gender, smoking history, surgical methods, pulmonary function index, pleural adhesion, pathologic diagnosis, side and site of resected lung were analyzed. By using univariate and multivariate analysis, we found the independent predictors of PAL after anatomic lung resection and subsequently established a clinical prediction model. Then, another 112 patients (group B), who underwent anatomic lung resection in different time by different team, were chosen to verify the accuracy of the prediction model. Receiver-operating characteristic (ROC) curve was constructed using the prediction model. Multivariate Logistic regression analysis was used to identify six clinical characteristics [BMI, gender, smoking history, forced expiratory volume in one second to forced vital capacity ratio (FEV1%), pleural adhesion, site of resection] as independent predictors of PAL after anatomic lung resection. The area under the ROC curve for our model was 0.886 (95%CI: 0.835-0.937). The best predictive P value was 0.299 with sensitivity of 78.5% and specificity of 93.2%. Our prediction model could accurately identify occurrence risk of PAL in patients after anatomic lung resection, which might allow for more effective use of intraoperative prophylactic strategies.
.

  3. Establishing gene models from the Pinus pinaster genome using gene capture and BAC sequencing.

    Seoane-Zonjic, Pedro; Cañas, Rafael A; Bautista, Rocío; Gómez-Maldonado, Josefa; Arrillaga, Isabel; Fernández-Pozo, Noé; Claros, M Gonzalo; Cánovas, Francisco M; Ávila, Concepción

    2016-02-27

    In the era of DNA throughput sequencing, assembling and understanding gymnosperm mega-genomes remains a challenge. Although drafts of three conifer genomes have recently been published, this number is too low to understand the full complexity of conifer genomes. Using techniques focused on specific genes, gene models can be established that can aid in the assembly of gene-rich regions, and this information can be used to compare genomes and understand functional evolution. In this study, gene capture technology combined with BAC isolation and sequencing was used as an experimental approach to establish de novo gene structures without a reference genome. Probes were designed for 866 maritime pine transcripts to sequence genes captured from genomic DNA. The gene models were constructed using GeneAssembler, a new bioinformatic pipeline, which reconstructed over 82% of the gene structures, and a high proportion (85%) of the captured gene models contained sequences from the promoter regulatory region. In a parallel experiment, the P. pinaster BAC library was screened to isolate clones containing genes whose cDNA sequence were already available. BAC clones containing the asparagine synthetase, sucrose synthase and xyloglucan endotransglycosylase gene sequences were isolated and used in this study. The gene models derived from the gene capture approach were compared with the genomic sequences derived from the BAC clones. This combined approach is a particularly efficient way to capture the genomic structures of gene families with a small number of members. The experimental approach used in this study is a valuable combined technique to study genomic gene structures in species for which a reference genome is unavailable. It can be used to establish exon/intron boundaries in unknown gene structures, to reconstruct incomplete genes and to obtain promoter sequences that can be used for transcriptional studies. A bioinformatics algorithm (GeneAssembler) is also provided as a

  4. [Experimental study on establishment of a simple model of rats crush injury-crush syndrome].

    Chen, Xi; Liu, Yuehong; Xu, Wei; Qin, Tingwu; Zhao, Luping; Liu, Shuping; Zhang, Yi; Tan, Hong; Zhou, Yu

    2013-01-01

    To establish a repeatable, simple, and effective model of rat crush injury and crush syndrome. A total of 42 female Sprague Dawley rats (2-month-old, (CS) so as to lay a foundation for further study on CS. weighing 160-180 g) were divided randomly into the control group (n=6) and experimental group (n=36). The rats of the experimental group were used to establish the crush injury and CS model in both lower limbs by self-made crush injury mould. The survival rate and hematuria rate were observed after decompression. The biochemical indexes of blood were measured at 2, 4, 8, 12, 24, and 48 hours after decompression. The samples of muscle, kidney, and heart were harvested for morphological observation. There was no treatment in the control group, and the same tests were performed. Seven rats died and 15 rats had hematuria during compression in the experimental group. Swelling of the lower limb and muscle tissue was observed in the survival rats after reperfusion. The liver function test results showed that the levels of alanine transaminase and aspartate aminotransferase in the experimental group were significantly higher than those in the control group (P congestion and swelling, renal tubular epithelial cell degeneration, edema, necrosis, and myoglobin tube type were found in the kidneys; and myocardial structure had no obvious changes. The method of the crush injury and CS model by self-made crush injury mould is a simple and effective procedure and the experimental result is stable. It is a simple method to establish an effective model of rats crush injury and CS.

  5. Establishment of an animal model of internal exposure to radioactive iodine

    Nitta, Y.; Hoshi, M. [Research Institute for Radiation Biology and Medicine, Hiroshima (Japan); Endo, S. [Hiroshima Univ., Hiroshima (Japan)

    2002-07-01

    Age is a potent modifier of the thyroid cancer risk at internal as well as external exposure. The short latency for the development of thyroid cancer in the post-Chernobyl cases proposes us to make sure the thyroid susceptibility to internal exposure at young ages. At the beginning of a large-scale carcinogenesis experiment for the induction of thyroid cancer by the internal exposure of 131 I into rats, we established the way to estimate absorbed doses in the thyroid and total body of rats at different ages: newborn, puberty and adult. Female rats of the Fischer 344 strain were exposed to {sub 131} I at the age of 1, 4 and 9 weeks, and have been kept for 16 days (twice of the {sub 131} I-half life) to draw kinetic curves of the isotope in the thyroid and total body. We drew the standard curve to estimate absorbed fraction of radioactivity from {beta} - and {gamma} -rays from the {sub 131} I in the thyroids of different sizes, because the thyroid size differs depending on age. Then we drew the standard curve to estimate absorbed doses in the thyroid and total body from the injected activities. Irradiation at 1 week of age caused heavier exposure than at 4 and 9 weeks of ages by 8 times in the thyroid. We tested the acute effects of radiation on the thyroid epithelium at the three ages. Radiation-induced apoptosis and post apoptotic cell proliferation of the thyroid epithelium were investigated. Apoptosis was not obvious in all the three age groups. Labeling index of the proliferating cell nuclear antigen (PCNA) increased in the 4 weeks old groups of both SD and IDD treatment. While in the 9 weeks old groups, it increased only by the treatment of IDD. One-week-old rats did not show any increase in the cell proliferation activity by{sub 60} Co {gamma} -irradiation, and did show small increase in the Sodium- {sub 131} I ( {sub 131} I)-injected IDD group.

  6. Comparison of various models on cancer rate and forecasting ...

    ADOWIE PERE

    model and the quadratic trend model and the results of the work compared. Data collected ... Keywords: Cancer, Tumor, Leukemia, Linear Regression, Mean Percentage Error. Cancer is a .... by a simple mathematical method. The quadratic ...

  7. Establishing a novel modeling tool: a python-based interface for a neuromorphic hardware system

    Daniel Brüderle

    2009-06-01

    Full Text Available Neuromorphic hardware systems provide new possibilities for the neuroscience modeling community. Due to the intrinsic parallelism of the micro-electronic emulation of neural computation, such models are highly scalable without a loss of speed. However, the communities of software simulator users and neuromorphic engineering in neuroscience are rather disjoint. We present a software concept that provides the possibility to establish such hardware devices as valuable modeling tools. It is based on the integration of the hardware interface into a simulator-independent language which allows for unified experiment descriptions that can be run on various simulation platforms without modification, implying experiment portability and a huge simplification of the quantitative comparison of hardware and simulator results. We introduce an accelerated neuromorphic hardware device and describe the implementation of the proposed concept for this system. An example setup and results acquired by utilizing both the hardware system and a software simulator are demonstrated.

  8. Establishing a novel modeling tool: a python-based interface for a neuromorphic hardware system.

    Brüderle, Daniel; Müller, Eric; Davison, Andrew; Muller, Eilif; Schemmel, Johannes; Meier, Karlheinz

    2009-01-01

    Neuromorphic hardware systems provide new possibilities for the neuroscience modeling community. Due to the intrinsic parallelism of the micro-electronic emulation of neural computation, such models are highly scalable without a loss of speed. However, the communities of software simulator users and neuromorphic engineering in neuroscience are rather disjoint. We present a software concept that provides the possibility to establish such hardware devices as valuable modeling tools. It is based on the integration of the hardware interface into a simulator-independent language which allows for unified experiment descriptions that can be run on various simulation platforms without modification, implying experiment portability and a huge simplification of the quantitative comparison of hardware and simulator results. We introduce an accelerated neuromorphic hardware device and describe the implementation of the proposed concept for this system. An example setup and results acquired by utilizing both the hardware system and a software simulator are demonstrated.

  9. Clinical Trial Design for Testing the Stem Cell Model for the Prevention and Treatment of Cancer

    Reddy, Rishindra M., E-mail: reddyrm@med.umich.edu [Medical Center, University of Michigan, 1500 E. Medical Center Drive, 2120 Taubman Center, Ann Arbor, MI 48109 (United States); Kakarala, Madhuri; Wicha, Max S. [Comprehensive Cancer Center, University of Michigan, 1500 E. Medical Center Drive, Ann Arbor, MI 48109 (United States)

    2011-06-20

    The cancer stem cell model introduces new strategies for the prevention and treatment of cancers. In cancers that appear to follow the stem cell model, pathways such as Wnt, Notch and Hedgehog may be targeted with natural compounds such as curcumin or drugs to reduce the risk of initiation of new tumors. Disease progression of established tumors could also potentially be inhibited by targeting the tumorigenic stem cells alone, rather than aiming to reduce overall tumor size. These new approaches mandate a change in the design of clinical trials and biomarkers chosen for efficacy assessment for preventative, neoadjuvant, adjuvant, and palliative treatments. Cancer treatments could be evaluated by assessing stem cell markers before and after treatment. Targeted stem cell specific treatment of cancers may not result in “complete” or “partial” responses radiologically, as stem cell targeting may not reduce the tumor bulk, but eliminate further tumorigenic potential. These changes are discussed using breast, pancreatic, and lung cancer as examples.

  10. Clinical Trial Design for Testing the Stem Cell Model for the Prevention and Treatment of Cancer

    Reddy, Rishindra M.; Kakarala, Madhuri; Wicha, Max S.

    2011-01-01

    The cancer stem cell model introduces new strategies for the prevention and treatment of cancers. In cancers that appear to follow the stem cell model, pathways such as Wnt, Notch and Hedgehog may be targeted with natural compounds such as curcumin or drugs to reduce the risk of initiation of new tumors. Disease progression of established tumors could also potentially be inhibited by targeting the tumorigenic stem cells alone, rather than aiming to reduce overall tumor size. These new approaches mandate a change in the design of clinical trials and biomarkers chosen for efficacy assessment for preventative, neoadjuvant, adjuvant, and palliative treatments. Cancer treatments could be evaluated by assessing stem cell markers before and after treatment. Targeted stem cell specific treatment of cancers may not result in “complete” or “partial” responses radiologically, as stem cell targeting may not reduce the tumor bulk, but eliminate further tumorigenic potential. These changes are discussed using breast, pancreatic, and lung cancer as examples

  11. Clozapine and GABA transmission in schizophrenia disease models: establishing principles to guide treatments.

    O'Connor, William T; O'Shea, Sean D

    2015-06-01

    Schizophrenia disease models are necessary to elucidate underlying changes and to establish new therapeutic strategies towards a stage where drug efficacy in schizophrenia (against all classes of symptoms) can be predicted. Here we summarise the evidence for a GABA dysfunction in schizophrenia and review the functional neuroanatomy of five pathways implicated in schizophrenia, namely the mesocortical, mesolimbic, ventral striopallidal, dorsal striopallidal and perforant pathways including the role of local GABA transmission and we describe the effect of clozapine on local neurotransmitter release. This review also evaluates psychotropic drug-induced, neurodevelopmental and environmental disease models including their compatibility with brain microdialysis. The validity of disease models including face, construct, etiological and predictive validity and how these models constitute theories about this illness is also addressed. A disease model based on the effect of the abrupt withdrawal of clozapine on GABA release is also described. The review concludes that while no single animal model is entirely successful in reproducing schizophreniform symptomatology, a disease model based on an ability to prevent and/or reverse the abrupt clozapine discontinuation-induced changes in GABA release in brain regions implicated in schizophrenia may be useful for hypothesis testing and for in vivo screening of novel ligands not limited to a single pharmacological class. Copyright © 2015 Elsevier Inc. All rights reserved.

  12. Models of crk adaptor proteins in cancer.

    Bell, Emily S; Park, Morag

    2012-05-01

    The Crk family of adaptor proteins (CrkI, CrkII, and CrkL), originally discovered as the oncogene fusion product, v-Crk, of the CT10 chicken retrovirus, lacks catalytic activity but engages with multiple signaling pathways through their SH2 and SH3 domains. Crk proteins link upstream tyrosine kinase and integrin-dependent signals to downstream effectors, acting as adaptors in diverse signaling pathways and cellular processes. Crk proteins are now recognized to play a role in the malignancy of many human cancers, stimulating renewed interest in their mechanism of action in cancer progression. The contribution of Crk signaling to malignancy has been predominantly studied in fibroblasts and in hematopoietic models and more recently in epithelial models. A mechanistic understanding of Crk proteins in cancer progression in vivo is still poorly understood in part due to the highly pleiotropic nature of Crk signaling. Recent advances in the structural organization of Crk domains, new roles in kinase regulation, and increased knowledge of the mechanisms and frequency of Crk overexpression in human cancers have provided an incentive for further study in in vivo models. An understanding of the mechanisms through which Crk proteins act as oncogenic drivers could have important implications in therapeutic targeting.

  13. Establishing an experimental model of photodynamic induced anterior ischemic optic neuropathy

    Runsheng Wang; Xiaodi Wang; Peilin Lü; Jianwei Bai; Jianzhou Wang; Xiaoqin Lei; Xiaoliang Zhou; Hongfen Sun; Aizhu Pan

    2006-01-01

    BACKGROUND: Scholars have supposed to establish animal models of optic neuropathy by pressing and partially amputating optic nerve, increasing intraocular pressure and injecting vasoconstrictor, etc., but the models are greatly different from anterior ischemia optic neuropathy. Therefore, a more ideal method is needed to establish animal model of anterior ischemic optic neuropathy (AION).OBJECTIVE: To establish AION models in rats, observe the functional changes of fundus, fundus fluorescein angiography (FFA), optical coherence tomography (OCT), flash visual evoked potential (F-VEP), and histopathologically confirm its reliability.DESIGN: A randomized control trial.SETTINGS: Department of Ophthalmology, Xi'an Fourth Hospital; Xi'an Institute of Ocular Fundus Diseases.MATERIALS: The experiments were carried out in the research room of Xi'an Institute of Ocular Fundus Diseases from February 2005 to May 2006. Thirty healthy male SD rats of 4-5 weeks old, weighing 140-160 g,were provided by the animal experimental center of the Fourth Military Medical University of Chinese PLA [SCXK (Military)2002-005], and those without eye disease examined by slit lamp and direct ophthalmoscope after mydriasis were enrolled. The conditions for feeding mice without special pathogen were strictly followed.The rats were randomly divided into blank control group (n =5), laser group (n =5), hematoporphyrin derivative (HPD) group and AION group (n =15), each group was numbered randomly. For each rat, the right eye was taken as the experimental eye, and the left one as the control one.METHODS: In the AION group, the rats were injected with HPD (10 mg/kg) via caudal vein, and then the optic discs were exposed to krypton red (647 nm, 80 mV) for 120 s, and the rats were in avoidance of light for 2 weeks postoperatively. Rats in the laser group were only exposed to krypton red (647 nm, 80 mV) for 120 s, and in avoidance of light for 2 weeks postoperatively; Those in the HPD group were only

  14. Personalized In Vitro and In Vivo Cancer Models to Guide Precision Medicine | Office of Cancer Genomics

    Precision medicine is an approach that takes into account the influence of individuals' genes, environment, and lifestyle exposures to tailor interventions. Here, we describe the development of a robust precision cancer care platform that integrates whole-exome sequencing with a living biobank that enables high-throughput drug screens on patient-derived tumor organoids. To date, 56 tumor-derived organoid cultures and 19 patient-derived xenograft (PDX) models have been established from the 769 patients enrolled in an Institutional Review Board-approved clinical trial.

  15. Establishment and characterization of Roberts syndrome and SC phocomelia model medaka (Oryzias latipes).

    Morita, Akihiro; Nakahira, Kumiko; Hasegawa, Taeko; Uchida, Kaoru; Taniguchi, Yoshihito; Takeda, Shunichi; Toyoda, Atsushi; Sakaki, Yoshiyuki; Shimada, Atsuko; Takeda, Hiroyuki; Yanagihara, Itaru

    2012-06-01

    Roberts syndrome and SC phocomelia (RBS/SC) are genetic autosomal recessive syndromes caused by establishment of cohesion 1 homolog 2 ( ESCO 2) mutation. RBS/SC appear to have a variety of clinical features, even with the same mutation of the ESCO2 gene. Here, we established and genetically characterized a medaka model of RBS/SC by reverse genetics. The RBS/SC model was screened from a mutant medaka library produced by the Targeting Induced Local Lesions in Genomes method. The medaka mutant carrying the homozygous mutation at R80S in the conserved region of ESCO2 exhibited clinical variety (i.e. developmental arrest with craniofacial and chromosomal abnormalities and embryonic lethality) as characterized in RBS/SC. Moreover, widespread apoptosis and downregulation of some gene expression, including notch1a, were detected in the R80S mutant. The R80S mutant is the animal model for RBS/SC and a valuable resource that provides the opportunity to extend knowledge of ESCO2. Downregulation of some gene expression in the R80S mutant is an important clue explaining non-correlation between genotype and phenotype in RBS/SC. © 2012 The Authors Development, Growth & Differentiation © 2012 Japanese Society of Developmental Biologists.

  16. Establishment and evaluation of a rat model of inhalation lung injury induced by ship smog

    Xin-xin DUAN

    2018-03-01

    Full Text Available Objective To establish and evaluate a rat model of inhalation lung injury induced by ship smog. Methods A rat model of inhalation lung injury was established by analyzing the composition of ship materials after combustion. Forty- two healthy male Wistar rats were randomly divided into normal control group and 2, 6, 12, 24, 48 and 72h groups (6 eachafter inhalation, these rats were killed at each time point, and the changes of arterial blood gas, coagulation function, the lung water content (% were detected. Macroscopic and microscopic changes in lung tissues were observed to judge the degree of lung injury. Results The main components after combustion of 7 kinds of nonmetal materials on ship included CO, CO2, H2S, NOx and other harmful gases in this study, AIKE in one gas detector was used to monitor O2, CO, CO2 and H2S, and their concentrations remained relatively stable within 15 minutes, and the injury time was 15 minutes. The rats presented with shortness of breath and mouth breathing. Smoke inhalation caused a significant hypoxemia, the concentration of blood COHb reached a peak value 2h and the lung water content (% did 6h after inhalation (P<0.05. It is metabolic acidosis in the early stage after inhalation, but metabolic acidosis combined with respiratory acidosis in the later period. Histopathological observation showed diffuse hemorrhage, edema and inflammatory cell infiltration in the lung tissue as manifestations of lung injury, and the injury did not recover at 72h after inhalation, the change of blood coagulation function was not statistically significant. Conclusion A rat model of inhalation lung injury induced by ship smog has been successfully established, and has the advantages of easy replication, stability and reliability, thus can be used to research and treat inhalation lung injury induced by ship smog in naval war environment and other cases. DOI: 10.11855/j.issn.0577-7402.2018.03.14

  17. Alpha particle emitters in cancer therapy: establishing the rationale and overcoming the difficulties

    Sgouros, G.

    1996-01-01

    Full text: Once a tumor has metastasized, the possibility of cure is significantly diminished, if not excluded. Since metastatic spread arises due to the release of single tumor cells or tumor cell clusters, treatment regimens following an overt metastasis must include agents that eradicate individual tumor cells and cell clusters or that prevent their dissemination. Alpha particles may be highly effective in eradicating rapidly accessible disease. The effectiveness of alpha particles arises because the amount of energy deposited per unit distance traveled (linear energy transfer or LET) is approximately 400 times greater than that of beta particles (80 keV/μm vs. 0.2 keV/μm). Each traversal of an alpha particle through a cell nucleus results in a very highly ionizing track. Cell survival studies have shown that alpha-particle killing is independent of oxygenation state or cell-cycle during irradiation and that as few as 1 to 6 tracks across the nucleus may result in cell death. Most studies with alpha-particle emitting radionuclides for therapy have examined either bismuth-212 or astatine-211. Both radionuclides are short-lived with 61 minute and 7.2 hour half-lives, respectively, yielding intermediates with 3-minute and 32 year half-lives, respectively. Both emit alpha particles whose range is 40 to 80 μm. Alpha-particle emitting radionuclides have been attached to antibodies against tumor cell associated antigen. Antibodies have been the most widely used vehicle for delivery of alpha particles due to their specificity. Bismuth-212 has demonstrated a significant curative potential with minimal toxicity. In an ascites tumor mouse model, specific targeting and 80% cure following injection of Bi-212-labeled antibody has been observed (Macklis RM et al, Science, 240:1024-1026, 1988). It is important to define the realm of applicability for alpha particle emitting radionuclides. The short half-life of most currently available radionuclides, limits their use to

  18. Case Studies of Community-Academic Partnerships Established Using the Give-Get Grid Model.

    Behringer, Bruce; Southerland, Jodi L; Plummer, Robert M

    2017-11-01

    While partnerships for health delivery and improvement are frequently described by their structure, goals, and plans, less attention is paid to the interactive relationships among partners or for larger stakeholder groups' coalition memberships. The Give-Get Grid group process tool can be used to assess each stakeholders' expected benefits ("gets") and contributions ("gives") needed to establish and maintain long-term, mutually advantageous community-academic partnerships. This article describes three case study experiences using the Give-Get Grid in real-world context to understand and generate ideas to address contemporary health promotion opportunities among a variety of stakeholders. The case studies address three distinct community health promotion opportunities: prevention of school-based adolescent obesity disparities, higher education health professions training programs in rural community-based settings, and methods for engaging community coalitions in state Comprehensive Cancer Control Programs. The case studies demonstrate the Give-Get Grid's utility in both planning and evaluating partnerships and documenting key elements for progress in health promotion initiatives built on long-term community-academic relationships. Steps are explained with practical lessons learned in using the Grid.

  19. Establishment of a blunt impact-induced brain injury model in rabbits

    LI Kui; CAO Yun-xing; YANG Yong-qiang; YIN Zhi-yong; ZHAO Hui; WANG Li-jun

    2012-01-01

    【Abstract】 Objective: To establish an animal model to replicate the blunt impact brain injury in forensic medicine. Methods: Twenty-four New Zealand white rabbits were randomly divided into control group (n=4), minor injury group (n=10) and severe injury group (n=10). Based on the BIM-Ⅱ Horizontal Bio-impact Machine, self-designed iron bar was used to produce blunt brain injury. Two rabbits from each injury group were randomly selected to monitor the change of in...

  20. [Etiological analysis and establishment of a discriminant model for lower respiratory tract infections in hospitalized patients].

    Chen, Y S; Lin, X H; Li, H R; Hua, Z D; Lin, M Q; Huang, W S; Yu, T; Lyu, H Y; Mao, W P; Liang, Y Q; Peng, X R; Chen, S J; Zheng, H; Lian, S Q; Hu, X L; Yao, X Q

    2017-12-12

    Objective: To analyze the pathogens of lower respiratory tract infection(LRTI) including bacterial, viral and mixed infection, and to establish a discriminant model based on clinical features in order to predict the pathogens. Methods: A total of 243 hospitalized patients with lower respiratory tract infections were enrolled in Fujian Provincial Hospital from April 2012 to September 2015. The clinical data and airway (sputum and/or bronchoalveolar lavage) samples were collected. Microbes were identified by traditional culture (for bacteria), loop-mediated isothermal amplification(LAMP) and gene sequencing (for bacteria and atypical pathogen), or Real-time quantitative polymerase chain reaction (Real-time PCR)for viruses. Finally, a discriminant model was established by using the discriminant analysis methods to help to predict bacterial, viral and mixed infections. Results: Pathogens were detected in 53.9% (131/243) of the 243 cases.Bacteria accounted for 23.5%(57/243, of which 17 cases with the virus, 1 case with Mycoplasma pneumoniae and virus), mainly Pseudomonas Aeruginosa and Klebsiella Pneumonia. Atypical pathogens for 4.9% (12/243, of which 3 cases with the virus, 1 case of bacteria and viruses), all were mycoplasma pneumonia. Viruses for 34.6% (84/243, of which 17 cases of bacteria, 3 cases with Mycoplasma pneumoniae, 1 case with Mycoplasma pneumoniae and bacteria) of the cases, mainly Influenza A virus and Human Cytomegalovirus, and other virus like adenovirus, human parainfluenza virus, respiratory syncytial virus, human metapneumovirus, human boca virus were also detected fewly. Seven parameters including mental status, using antibiotics prior to admission, complications, abnormal breath sounds, neutrophil alkaline phosphatase (NAP) score, pneumonia severity index (PSI) score and CRUB-65 score were enrolled after univariate analysis, and discriminant analysis was used to establish the discriminant model by applying the identified pathogens as the

  1. Models of breast cancer: quo vadis, animal modeling?

    Wagner, Kay-Uwe

    2004-01-01

    Rodent models for breast cancer have for many decades provided unparalleled insights into cellular and molecular aspects of neoplastic transformation and tumorigenesis. Despite recent improvements in the fidelity of genetically engineered mice, rodent models are still being criticized by many colleagues for not being 'authentic' enough to the human disease. Motives for this criticism are manifold and range from a very general antipathy against the rodent model system to well-founded arguments that highlight physiological variations between species. Newly proposed differences in genetic pathways that cause cancer in humans and mice invigorated the ongoing discussion about the legitimacy of the murine system to model the human disease. The present commentary intends to stimulate a debate on this subject by providing the background about new developments in animal modeling, by disputing suggested limitations of genetically engineered mice, and by discussing improvements but also ambiguous expectations on the authenticity of xenograft models to faithfully mimic the human disease

  2. Antipsychotic potential of quinazoline ErbB1 inhibitors in a schizophrenia model established with neonatal hippocampal lesioning.

    Mizuno, Makoto; Iwakura, Yuriko; Shibuya, Masako; Zheng, Yingjun; Eda, Takeyoshi; Kato, Taisuke; Takasu, Yohei; Nawa, Hiroyuki

    2010-01-01

    Hyper-signaling of the epidermal growth factor receptor family (ErbB) is implicated in the pathophysiology of schizophrenia. Various quinazoline inhibitors targeting ErbB1 or ErbB2 - 4 have been developed as anti-cancer agents and might be useful for antipsychotic treatment. In the present study, we used an animal model of schizophrenia established by neonatal hippocampal lesioning and evaluated the neurobehavioral consequences of ErbB1-inhibitor treatment. Subchronic administration of the ErbB1 inhibitor ZD1839 to the cerebroventricle of rats receiving neonatal hippocampal lesioning ameliorated deficits in prepulse inhibition as well as those in the latent inhibition of tone-dependent fear learning. There were no apparent adverse effects on basal learning scores or locomotor activity, however. The administration of other ErbB1 inhibitors, PD153035 and OSI-774, similarly attenuated the prepulse inhibition impairment of this animal model. In parallel, there were decreases in ErbB1 phosphorylation in animals treated with ErbB1 inhibitors. These results indicate an antipsychotic potential of quinazoline ErbB1 inhibitors. ErbB receptor tyrosine kinases may be novel therapeutic targets for schizophrenia or its related psychotic symptoms.

  3. Anxiety in the context of cancer: A systematic review and development of an integrated model.

    Curran, Leah; Sharpe, Louise; Butow, Phyllis

    2017-08-01

    Anxiety is common in the context of cancer, but there are few theoretical models that apply to people with cancer across the trajectory of their illness. The aims of this review are to identify existing theories and to propose an integrated model of cancer-related anxiety. Using a systematic literature search of Medline, Premedline and PsycINFO databases, we identified nine theoretical models of anxiety in the context of cancer. We reviewed these for psychological concepts that fell under five themes: pre-existing schema, the inherent nature of cancer, cognitive factors, coping responses and contextual factors. From these themes, we integrated concepts from different models to develop a theoretical framework to explain the development and maintenance of anxiety in the context of cancer. The resulting model suggests that pre-existing schema, past experiences of cancer, an intolerance of uncertainty and meta-cognitive beliefs about worry interact with the inherent nature of cancer to produce overwhelming distress. The distress activates cognitive processes characterized by vigilance, worry and rumination. Attempts to cope by re-establishing control, and a pattern of vigilance to cancer-related cues and/or avoidance reinforce anxiety, in the context of a range of systemic factors that can either buffer against or worsen the anxiety. Copyright © 2017. Published by Elsevier Ltd.

  4. New model for gastroenteropancreatic large-cell neuroendocrine carcinoma: establishment of two clinically relevant cell lines.

    Andreas Krieg

    Full Text Available Recently, a novel WHO-classification has been introduced that divided gastroenteropancreatic neuroendocrine neoplasms (GEP-NEN according to their proliferation index into G1- or G2-neuroendocrine tumors (NET and poorly differentiated small-cell or large-cell G3-neuroendocrine carcinomas (NEC. Our knowledge on primary NECs of the GEP-system is limited due to the rarity of these tumors and chemotherapeutic concepts of highly aggressive NEC do not provide convincing results. The aim of this study was to establish a reliable cell line model for NEC that could be helpful in identifying novel druggable molecular targets. Cell lines were established from liver (NEC-DUE1 or lymph node metastases (NEC-DUE2 from large cell NECs of the gastroesophageal junction and the large intestine, respectively. Morphological characteristics and expression of neuroendocrine markers were extensively analyzed. Chromosomal aberrations were mapped by array comparative genomic hybridization and DNA profiling was analyzed by DNA fingerprinting. In vitro and in vivo tumorigenicity was evaluated and the sensitivity against chemotherapeutic agents assessed. Both cell lines exhibited typical morphological and molecular features of large cell NEC. In vitro and in vivo experiments demonstrated that both cell lines retained their malignant properties. Whereas NEC-DUE1 and -DUE2 were resistant to chemotherapeutic drugs such as cisplatin, etoposide and oxaliplatin, a high sensitivity to 5-fluorouracil was observed for the NEC-DUE1 cell line. Taken together, we established and characterized the first GEP large-cell NEC cell lines that might serve as a helpful tool not only to understand the biology of these tumors, but also to establish novel targeted therapies in a preclinical setup.

  5. Matrix Methods and Models of Economic Analysis in the Marketing Activity of Higher Educational Establishments

    Natalia Stebliuk

    2018-05-01

    Full Text Available On the present stage of the development of educational environment, it is necessary to use the scientific tools for understanding the market patterns of the interaction of demand and supply of educational services, which will allow not only to navigate the consumer preferences but also to form them. It is in these circumstances that it is extremely important to study changes in the volume of demand for educational services in order to adapt them to the system of higher education. The aim of the article is to substantiate the theoretical positions and develop practical recommendations for the definition of the competitive marketing strategy of higher education organizations in the market of educational services with the help of modern approaches and methods of economic-mathematical modeling. The practical significance of the obtained results is the introduction of methodological provisions for forecasting the demand and supply of educational services for higher educational establishments. The complexity and interdependence of managerial problems in the system of higher education require new ideas and approaches, which necessitates the search for new definite solutions, namely: the research paper offers the method of optimal distribution of budgetary places of the university by means of practical application of the theory of system constraints and the theory of fuzzy sets. Along with that, the calculation of the optimal number of students of the corresponding specialty with the help of cluster analysis has been carried out. In addition, an important place for improvement and development is taken by the economics and mathematical methods and methods of linear programming, they are effective means of identifying the most influential factors in achieving the goals of a higher educational establishment and justifying the marketing strategy of its development in modern conditions. To predict the quantitative values of social and economic indicators

  6. Establishment of a rat model of portal vein ligation combined with in situ splitting.

    Yao, Libin; Li, Chonghui; Ge, Xinlan; Wang, Hongdong; Xu, Kesen; Zhang, Aiqun; Dong, Jiahong

    2014-01-01

    Portal vein ligation (PVL) combined with in situ splitting (ISS) has been shown to induce remarkable liver regeneration in patients. The purpose of this study was to establish a model of PVL+ISS in rats for exploring the possible mechanisms of liver regeneration using these techniques. Rats were randomly assigned to three experimental groups: selective PVL, selective PVL+ISS and sham operation. The hepatic regeneration rate (HRR), Ki-67, liver biochemical determinations and histopathology were assessed at 24, 48, and 72 h and 7 days after the operation. The microcirculation of the median lobes before and after ISS was examined by laser speckle contrast imaging. Meanwhile, cytokines such as TNF-α, IL-6, HGF and HSP70 in regenerating liver lobes at 24 h was investigated by RT-PCR and ELISA. The HRR of PVL+ISS was much higher than that of the PVL at 72 h and 7 days after surgery (pprotein levels of TNF-α, IL-6 and HGF in regenerating liver lobes were higher in the PVL+ISS than the PVL alone. The higher HRR in the PVL+ISS compared with the PVL confirmed that we had successfully established a PVL+ISS model in rats. The possible mechanisms included the reduced microcirculation blood perfusion of the left median lobe and up-regulation of cytokines in the regenerating lobes after ISS.

  7. Establishment and characterization of a differentiated epithelial cell culture model derived from the porcine cervix uteri

    Miessen Katrin

    2012-03-01

    Full Text Available Abstract Background Cervical uterine epithelial cells maintain a physiological and pathogen-free milieu in the female mammalian reproductive tract and are involved in sperm-epithelium interaction. Easily accessible, differentiated model systems of the cervical epithelium are not yet available to elucidate the underlying molecular mechanisms within these highly specialized cells. Therefore, the aim of the study was to establish a cell culture of the porcine cervical epithelium representing in vivo-like properties of the tissue. Results We tested different isolation methods and culture conditions and validated purity of the cultured cells by immunohistochemistry against keratins. We could reproducibly culture pure epithelial cells from cervical tissue explants. Based on a morphology score and the WST-1 Proliferation Assay, we optimized the growth medium composition. Primary porcine cervical cells performed best in conditioned Ham's F-12, containing 10% FCS, EGF and insulin. After cultivation in an air-liquid interface for three weeks, the cells showed a discontinuously multilayered phenotype. Finally, differentiation was validated via immunohistochemistry against beta catenin. Mucopolysaccharide production could be shown via alcian blue staining. Conclusions We provide the first suitable protocol to establish a differentiated porcine epithelial model of the cervix uteri, based on easily accessible cells using slaughterhouse material.

  8. Establishment and characterization of a differentiated epithelial cell culture model derived from the porcine cervix uteri.

    Miessen, Katrin; Einspanier, Ralf; Schoen, Jennifer

    2012-03-19

    Cervical uterine epithelial cells maintain a physiological and pathogen-free milieu in the female mammalian reproductive tract and are involved in sperm-epithelium interaction. Easily accessible, differentiated model systems of the cervical epithelium are not yet available to elucidate the underlying molecular mechanisms within these highly specialized cells. Therefore, the aim of the study was to establish a cell culture of the porcine cervical epithelium representing in vivo-like properties of the tissue. We tested different isolation methods and culture conditions and validated purity of the cultured cells by immunohistochemistry against keratins. We could reproducibly culture pure epithelial cells from cervical tissue explants. Based on a morphology score and the WST-1 Proliferation Assay, we optimized the growth medium composition. Primary porcine cervical cells performed best in conditioned Ham's F-12, containing 10% FCS, EGF and insulin. After cultivation in an air-liquid interface for three weeks, the cells showed a discontinuously multilayered phenotype. Finally, differentiation was validated via immunohistochemistry against beta catenin. Mucopolysaccharide production could be shown via alcian blue staining. We provide the first suitable protocol to establish a differentiated porcine epithelial model of the cervix uteri, based on easily accessible cells using slaughterhouse material.

  9. [Establishment of model of traditional Chinese medicine injections post-marketing safety monitoring].

    Guo, Xin-E; Zhao, Yu-Bin; Xie, Yan-Ming; Zhao, Li-Cai; Li, Yan-Feng; Hao, Zhe

    2013-09-01

    To establish a nurse based post-marketing safety surveillance model for traditional Chinese medicine injections (TCMIs). A TCMIs safety monitoring team and a research hospital team engaged in the research, monitoring processes, and quality control processes were established, in order to achieve comprehensive, timely, accurate and real-time access to research data, to eliminate errors in data collection. A triage system involving a study nurse, as the first point of contact, clinicians and clinical pharmacists was set up in a TCM hospital. Following the specified workflow involving labeling of TCM injections and using improved monitoring forms it was found that there were no missing reports at the ratio of error was zero. A research nurse as the first and main point of contact in post-marketing safety monitoring of TCM as part of a triage model, ensures that research data collected has the characteristics of authenticity, accuracy, timeliness, integrity, and eliminate errors during the process of data collection. Hospital based monitoring is a robust and operable process.

  10. Establishment and application of rat model of acute β-irradiated skin injury

    Shen Guoliang; Lu Xing'an; Tang Jun; Wang Xiuzhen; Wu Shiliang; Tian Ye

    2006-01-01

    Objective: To establish an experimental rat model of acute β-irradiated skin injury and to study the effects of superoxide dismutase (SOD) on wound healing. Methods: Areas of buttock skin (20 mm x 40 mm) of 40 male SD rats were irradiated with 45 Gy/β-rays generated by linear accelerator, and then the forty rats were divided into two groups randomly: treatment group administrated with SOD (n=20) and control group administrated with normal saline (NS) (n=20). The wound healing time and rate were observed. The pathological changes were observed by light microscopy. The expressions of VEGF (vascular endothelial growth factor) and bFGF (basic fibroblast growth factor) were determined by SP immunohistochemical method. Results: The deep second-degree burns was observed following 45 Gy irradiation. The wound healing time in treatment group was shorter than that of the control group (P<0.05). Strongly positive (+ + +) expression of VEGF, bFGF in treatment group and positive (+ +) expression of VEGF, bFGF in the control group were observed 6 weeks, 7 weeks and 8 weeks after the irradiation, while only weakly positive (+) expressions of VEGF and bFGF in both groups 4 weeks, 5 weeks and 9 weeks after the irradiation. Conclusions: The wound model of acute β-irradiated skin injury in rat was established and used in study of the effect of medicine on wound healing. SOD can promote the wound healing of acute β-irradiated skin injury. (authors)

  11. Establishment of tunnel-boring machine disk cutter rock-breaking model from energy perspective

    Liwei Song

    2015-12-01

    Full Text Available As the most important cutting tools during tunnel-boring machine tunneling construction process, V-type disk cutter’s rock-breaking mechanism has been researched by many scholars all over the world. Adopting finite element method, this article focused on the interaction between V-type disk cutters and the intact rock to carry out microscopic parameter analysis methods: first, the stress model of rock breaking was established through V-type disk cutter motion trajectory analysis; second, based on the incremental theorem of the elastic–plastic theory, the strain model of the relative changes of rock displacement during breaking process was created. According to the principle of admissible work by energy method of the elastic–plastic theory to analyze energy transfer rules in the process of breaking rock, rock-breaking force of the V-type disk cutter could be regarded as the external force in the rock system. Finally, by taking the rock system as the reference object, the total potential energy equivalent model of rock system was derived to obtain the forces of the three directions acting on V-type disk cutter during the rock-breaking process. This derived model, which has been proved to be effective and scientific through comparisons with some original force models and by comparative analysis with experimental data, also initiates a new research strategy taking the view of the micro elastic–plastic theory to study the rock-breaking mechanism.

  12. Establishment of atherosclerotic model and USPIO enhanced MRI techniques study in rabbits

    Li Yonggang; Zhu Mo; Dai Yinyu; Chen Jianhua; Guo Liang; Ni Jiankun

    2010-01-01

    Objective: To explore the methods of establishment of atherosclerotic model and USPIO enhanced MRI techniques in rabbits. Methods: Thirty New Zealand male rabbits were divided randomly into two groups: 20 animals in the experiment group, 10 animals in the control group. Animal model of atherosclerosis was induced with aortic balloon endothelial injury and high-fat diet feeding. There was no intervention with the rabbits in control group. MRI examination included plan scan, USPIO enhanced black-blood sequences and white-blood sequence. The features of the plaques was analyzed in the experimental group and the effection on the image quality of different coils, sequences and parameters and a statistical study was also analyzed. Results: Animal model of atherosclerosis was successfully made in 12 rabbits and most plaques located in the abdomen aorta. There were 86 plaques within the scanning scope among which 67 plaques were positive to the Prussian blue staining. The image quality of knee joint coil was better than that of other coils. Although there was no difference in the detection of numbers of AS plaques between USPIO enhanced black-blood sequences and white-blood sequence (P > 0.05), blackblood sequences was superior to white-blood sequence in the demonstration of the components of plaque. Conclusion: The method of aortic balloon endothelial injury and high-fat diet feeding can easily establish the AS model in rabbits with a shorter period and it may be used for controlling the location of the plaques. USPIO enhanced MRI sequences has high sensitivity in the detection of the AS plauqes and can reveal the component of AS plaques. The optimization of MRI techniques is very important in the improvement of the image quality and the detection of the plaques. (authors)

  13. [Establishment of Schatzker classification digital models of tibial plateau fractures and its application on virtual surgery].

    Liu, Yong-gang; Zuo, Li-xin; Pei, Guo-xian; Dai, Ke; Sang, Jing-wei

    2013-08-20

    To explore the establishment of Schatzker classification digital model of tibial plateau fractures and its application in virtual surgery. Proximal tibial of one healthy male volunteer was examined with 64-slice spiral computed tomography (CT). The data were processed by software Mimics 10.01 and a model of proximal tibia was reconstructed. According to the Schatzker classification criteria of tibial plateau fractures, each type of fracture model was simulated.Screen-captures of fracture model were saved from different directions.Each type of fracture model was exported as video mode.Fracture model was imported into FreeForm modeling system.With a force feedback device, a surgeon could conduct virtual fracture operation simulation.Utilizing the GHOST of FreeForm modeling system, the software of virtual cutting, fracture reduction and fixation was developed.With a force feedback device PHANTOM, a surgeon could manipulate virtual surgical instruments and fracture classification model and simulate surgical actions such as assembly of surgical instruments, drilling, implantation of screw, reduction of fracture, bone grafting and fracture fixation, etc. The digital fracture model was intuitive, three-dimensional and realistic and it had excellent visual effect.Fracture could be observed and charted from optional direction and angle.Fracture model could rotate 360 ° in the corresponding video mode. The virtual surgical environment had a strong sense of reality, immersion and telepresence as well as good interaction and force feedback function in the FreeForm modeling system. The user could make the corresponding decisions about surgical method and choice of internal fixation according to the specific type of tibial plateau fracture as well as repeated operational practice in virtual surgery system. The digital fracture model of Schatzker classification is intuitive, three-dimensional, realistic and dynamic. The virtual surgery systems of Schatzker classifications make

  14. Establishing national noncommunicable disease surveillance in a developing country: a model for small island nations

    Angela M. Rose

    Full Text Available ABSTRACT Objective To describe the surveillance model used to develop the first national, population-based, multiple noncommunicable disease (NCD registry in the Caribbean (one of the first of its kind worldwide; registry implementation; lessons learned; and incidence and mortality rates from the first years of operation. Methods Driven by limited national resources, this initiative of the Barbados Ministry of Health (MoH, in collaboration with The University of the West Indies, was designed to collect prospective data on incident stroke and acute myocardial infarction (MI (heart attack cases from all health care facilities in this small island developing state (SIDS in the Eastern Caribbean. Emphasis is on tertiary and emergency health care data sources. Incident cancer cases are obtained retrospectively, primarily from laboratories. Deaths are collected from the national death register. Results Phased introduction of the Barbados National Registry for Chronic NCDs (“the BNR” began with the stroke component (“BNR–Stroke,” 2008, followed by the acute MI component (“BNR–Heart,” 2009 and the cancer component (“BNR–Cancer,” 2010. Expected case numbers projected from prior studies estimated an average of 378 first-ever stroke, 900 stroke, and 372 acute MI patients annually, and registry data showed an annual average of about 238, 593, and 349 patients respectively. There were 1 204 tumors registered in 2008, versus the expected 1 395. Registry data were used to identify public health training themes. Success required building support from local health care professionals and creating island-wide registry awareness. With spending of approximately US$ 148 per event for 2 200 events per year, the program costs the MoH about US$ 1 per capita annually. Conclusions Given the limited absolute health resources available to SIDS, combined surveillance should be considered for building a national NCD evidence base. With prevalence

  15. Design and Establishment of Quality Model of Fundamental Geographic Information Database

    Ma, W.; Zhang, J.; Zhao, Y.; Zhang, P.; Dang, Y.; Zhao, T.

    2018-04-01

    In order to make the quality evaluation for the Fundamental Geographic Information Databases(FGIDB) more comprehensive, objective and accurate, this paper studies and establishes a quality model of FGIDB, which formed by the standardization of database construction and quality control, the conformity of data set quality and the functionality of database management system, and also designs the overall principles, contents and methods of the quality evaluation for FGIDB, providing the basis and reference for carry out quality control and quality evaluation for FGIDB. This paper designs the quality elements, evaluation items and properties of the Fundamental Geographic Information Database gradually based on the quality model framework. Connected organically, these quality elements and evaluation items constitute the quality model of the Fundamental Geographic Information Database. This model is the foundation for the quality demand stipulation and quality evaluation of the Fundamental Geographic Information Database, and is of great significance on the quality assurance in the design and development stage, the demand formulation in the testing evaluation stage, and the standard system construction for quality evaluation technology of the Fundamental Geographic Information Database.

  16. Establishing a coherent and replicable measurement model of the Edinburgh Postnatal Depression Scale.

    Martin, Colin R; Redshaw, Maggie

    2018-06-01

    The 10-item Edinburgh Postnatal Depression Scale (EPDS) is an established screening tool for postnatal depression. Inconsistent findings in factor structure and replication difficulties have limited the scope of development of the measure as a multi-dimensional tool. The current investigation sought to robustly determine the underlying factor structure of the EPDS and the replicability and stability of the most plausible model identified. A between-subjects design was used. EPDS data were collected postpartum from two independent cohorts using identical data capture methods. Datasets were examined with confirmatory factor analysis, model invariance testing and systematic evaluation of relational and internal aspects of the measure. Participants were two samples of postpartum women in England assessed at three months (n = 245) and six months (n = 217). The findings showed a three-factor seven-item model of the EPDS offered an excellent fit to the data, and was observed to be replicable in both datasets and invariant as a function of time point of assessment. Some EPDS sub-scale scores were significantly higher at six months. The EPDS is multi-dimensional and a robust measurement model comprises three factors that are replicable. The potential utility of the sub-scale components identified requires further research to identify a role in contemporary screening practice. Copyright © 2018 The Authors. Published by Elsevier B.V. All rights reserved.

  17. Sequence-structure relationships in RNA loops: establishing the basis for loop homology modeling.

    Schudoma, Christian; May, Patrick; Nikiforova, Viktoria; Walther, Dirk

    2010-01-01

    The specific function of RNA molecules frequently resides in their seemingly unstructured loop regions. We performed a systematic analysis of RNA loops extracted from experimentally determined three-dimensional structures of RNA molecules. A comprehensive loop-structure data set was created and organized into distinct clusters based on structural and sequence similarity. We detected clear evidence of the hallmark of homology present in the sequence-structure relationships in loops. Loops differing by structures. Thus, our results support the application of homology modeling for RNA loop model building. We established a threshold that may guide the sequence divergence-based selection of template structures for RNA loop homology modeling. Of all possible sequences that are, under the assumption of isosteric relationships, theoretically compatible with actual sequences observed in RNA structures, only a small fraction is contained in the Rfam database of RNA sequences and classes implying that the actual RNA loop space may consist of a limited number of unique loop structures and conserved sequences. The loop-structure data sets are made available via an online database, RLooM. RLooM also offers functionalities for the modeling of RNA loop structures in support of RNA engineering and design efforts.

  18. Establishment and Characterization of UTI and CAUTI in a Mouse Model.

    Conover, Matt S; Flores-Mireles, Ana L; Hibbing, Michael E; Dodson, Karen; Hultgren, Scott J

    2015-06-23

    Urinary tract infections (UTI) are highly prevalent, a significant cause of morbidity and are increasingly resistant to treatment with antibiotics. Females are disproportionately afflicted by UTI: 50% of all women will have a UTI in their lifetime. Additionally, 20-40% of these women who have an initial UTI will suffer a recurrence with some suffering frequent recurrences with serious deterioration in the quality of life, pain and discomfort, disruption of daily activities, increased healthcare costs, and few treatment options other than long-term antibiotic prophylaxis. Uropathogenic Escherichia coli (UPEC) is the primary causative agent of community acquired UTI. Catheter-associated UTI (CAUTI) is the most common hospital acquired infection accounting for a million occurrences in the US annually and dramatic healthcare costs. While UPEC is also the primary cause of CAUTI, other causative agents are of increased significance including Enterococcus faecalis. Here we utilize two well-established mouse models that recapitulate many of the clinical characteristics of these human diseases. For UTI, a C3H/HeN model recapitulates many of the features of UPEC virulence observed in humans including host responses, IBC formation and filamentation. For CAUTI, a model using C57BL/6 mice, which retain catheter bladder implants, has been shown to be susceptible to E. faecalis bladder infection. These representative models are being used to gain striking new insights into the pathogenesis of UTI disease, which is leading to the development of novel therapeutics and management or prevention strategies.

  19. Establishment of a hepatic cirrhosis and portal hypertension model by hepatic arterial perfusion with 80% alcohol.

    Wang, Lei; He, Fu-Liang; Liu, Fu-Quan; Yue, Zhen-Dong; Zhao, Hong-Wei

    2015-08-28

    To determine the feasibility and safety of establishing a porcine hepatic cirrhosis and portal hypertension model by hepatic arterial perfusion with 80% alcohol. Twenty-one healthy Guizhou miniature pigs were randomly divided into three experimental groups and three control groups. The pigs in the three experimental groups were subjected to hepatic arterial perfusion with 7, 12 and 17 mL of 80% alcohol, respectively, while those in the three control groups underwent hepatic arterial perfusion with 7, 12 and 17 mL of saline, respectively. Hepatic arteriography and direct portal phlebography were performed on all animals before and after perfusion, and the portal venous pressure and diameter were measured before perfusion, immediately after perfusion, and at 2, 4 and 6 wk after perfusion. The following procedures were performed at different time points: routine blood sampling, blood biochemistry, blood coagulation and blood ammonia tests before surgery, and at 2, 4 and 6 wk after surgery; hepatic biopsy before surgery, within 6 h after surgery, and at 1, 2, 3, 4 and 5 wk after surgery; abdominal enhanced computed tomography examination before surgery and at 6 wk after surgery; autopsy and multi-point sampling of various liver lobes for histological examination at 6 wk after surgery. In experimental group 1, different degrees of hepatic fibrosis were observed, and one pig developed hepatic cirrhosis. In experimental group 2, there were cases of hepatic cirrhosis, different degrees of increased portal venous pressure, and intrahepatic portal venous bypass, but neither extrahepatic portal-systemic bypass circulation nor death occurred. In experimental group 3, two animals died and three animals developed hepatic cirrhosis, and different degrees of increased portal venous pressure and intrahepatic portal venous bypass were also observed, but there was no extrahepatic portal-systemic bypass circulation. It is feasible to establish an animal model of hepatic cirrhosis and

  20. The development and refinement of models of less established and more established high school environmental service-learning programs in Florida

    Malikova, Yuliya

    2005-07-01

    Environmental Service-Learning (Env. S-L) appears to show great promise and practitioners tout its benefits, although there have been fewer than ten studies in this emerging area of environmental education. The overall study purpose was to describe the nature, status, and effects of Grade 9--16 Env. S-L programs in Florida, and develop descriptive models of those programs. The purpose of Phase I was to describe these programs and associated partnerships. Based on Phase I results, the purpose of Phase II was to develop, compare, and refine models for less and more established high school programs. This study involved: (1) defining the population of Florida 9--16 Env. S-L programs (Phase I); (2) developing and administering program surveys (Phase I, quantitative); (3) analyzing Phase I survey data and identifications of options for Phase II (Intermediate stage); (4) designing and implementing methodology for further data collection (Phase II, qualitative); (5) refining and finalizing program models (Phase II, descriptive); and (6) summarizing program data, changes, and comparisons. This study revealed that Env. S-L has been practiced in a variety of ways at the high school and college levels in Florida. There, the number of high school programs, and participating teachers and students has been growing. Among others, major program features include block scheduling, indirect S-L activities, external funding sources, and formal and ongoing community partnerships. Findings based on self-reported program assessment results indicate that S-L has had positive effects on students across Furco's S-L outcome domains (i.e., academic achievement/success, school participation/behavior, carrier development, personal development, interpersonal development, ethical/moral development, and development of civic responsibility). Differences existed between less established and more established Env. S-L programs. Less established programs had relatively few participating teachers

  1. [Establish Assessment Model of 18 Years of Age in Chinese Han Population by Mandibular Third Molar].

    Fan, Fei; Dai, Xin-hua; Wang, Liang; Li, Yuan; Zhang, Kui; Deng, Zhen-hua

    2016-02-01

    To explore the value of estimating chronologic age based on the grades of mandibular third molar development. To evaluate whether mandibular third molar could be used as an indicator for estimating the age under or over 18 years. The mineralization status of mandibular third molar of 1 845 individuals aged 10 - 30 was graded and marked based on Demirjian's classification of grades reformed by Orhan. Gender difference was examined by t-test. A cubic regression model was established to analyze the correlation between third molar and chronologic age. Each grade of age cumulative distribution diagram and ROC curve was respectively performed to evaluate the relationship between third molar and the age of 18. Using Bayes discriminant analysis, an equation was established for estimating the age of 18. The inner-rater reliability was 0.903. Statistical analysis showed a moderate correlation between age and grade. Significant differences of both genders were found only in grade D and H (P Third molar development shows a high correlation with age, and combined with other indicators, it can be used to estimate the age of 18.

  2. Establishment of primary cultures for mouse ameloblasts as a model of their lifetime

    Suzawa, Tetsuo; Itoh, Nao; Takahashi, Naoyuki; Katagiri, Takenobu; Morimura, Naoko; Kobayashi, Yasuna; Yamamoto, Toshinori; Kamijo, Ryutaro

    2006-01-01

    To understand how the properties of ameloblasts are spatiotemporally regulated during amelogenesis, two primary cultures of ameloblasts in different stages of differentiation were established from mouse enamel epithelium. Mouse primary ameloblasts (MPAs) prepared from immature enamel epithelium (MPA-I) could proliferate, whereas those from mature enamel epithelium (MPA-M) could not. MPA-M but not MPA-I caused apoptosis during culture. The mRNA expression of amelogenin, a marker of immature ameloblasts, was down-regulated, and that of enamel matrix serine proteiase-1, a marker of mature ameloblasts, was induced in MPA-I during culture. Using green fluorescence protein as a reporter, a visualized reporter system was established to analyze the promoter activity of the amelogenin gene. The region between -1102 bp and -261 bp was required for the reporter expression in MPA-I. These results suggest that MPAs are valuable in vitro models for investigation of ameloblast biology, and that the visualized system is useful for promoter analysis in MPAs

  3. Improvement of the projection models for radiogenic cancer risk

    Tong Jian

    2005-01-01

    Calculations of radiogenic cancer risk are based on the risk projection models for specific cancer sites. Improvement has been made for the parameters used in the previous models including introductions of mortality and morbidity risk coefficients, and age-/ gender-specific risk coefficients. These coefficients have been applied to calculate the radiogenic cancer risks for specific organs and radionuclides under different exposure scenarios. (authors)

  4. Radiation Response of Cancer Stem-Like Cells From Established Human Cell Lines After Sorting for Surface Markers

    Al-Assar, Osama; Muschel, Ruth J.; Mantoni, Tine S.; McKenna, W. Gillies; Brunner, Thomas B.

    2009-01-01

    Purpose: A subpopulation of cancer stem-like cells (CSLC) is hypothesized to exist in different cancer cell lines and to mediate radioresistance in solid tumors. Methods and Materials: Cells were stained for CSLC markers and sorted (fluorescence-activated cell sorter/magnetic beads) to compare foci and radiosensitivity of phosphorylated histone H2AX at Ser 139 (γ-H2AX) in sorted vs. unsorted populations in eight cell lines from different organs. CSLC properties were examined using anchorage-independent growth and levels of activated Notch1. Validation consisted of testing tumorigenicity and postirradiation enrichment of CSLC in xenograft tumors. Results: The quantity of CSLC was generally in good agreement with primary tumors. CSLC from MDA-MB-231 (breast) and Panc-1 and PSN-1 (both pancreatic) cells had fewer residual γ-H2AX foci than unsorted cells, pointing to radioresistance of CSLC. However, only MDA-MB-231 CSLC were more radioresistant than unsorted cells. Furthermore, MDA-MB-231 CSLC showed enhanced anchorage-independent growth and overexpression of activated Notch1 protein. The expression of cancer stem cell surface markers in the MDA-MB-231 xenograft model was increased after exposure to fractionated radiation. In contrast to PSN-1 cells, a growth advantage for MDA-MB-231 CSLC xenograft tumors was found compared to tumors arising from unsorted cells. Conclusions: CSLC subpopulations showed no general radioresistant phenotype, despite the quantities of CSLC subpopulations shown to correspond relatively well in other reports. Likewise, CSLC characteristics were found in some but not all of the tested cell lines. The reported problems in testing for CSLC in cell lines may be overcome by additional techniques, beyond sorting for markers.

  5. Establishment of a general NAFLD scoring system for rodent models and comparison to human liver pathology.

    Wen Liang

    Full Text Available The recently developed histological scoring system for non-alcoholic fatty liver disease (NAFLD by the NASH Clinical Research Network (NASH-CRN has been widely used in clinical settings, but is increasingly employed in preclinical research as well. However, it has not been systematically analyzed whether the human scoring system can directly be converted to preclinical rodent models. To analyze this, we systematically compared human NAFLD liver pathology, using human liver biopsies, with liver pathology of several NAFLD mouse models. Based upon the features pertaining to mouse NAFLD, we aimed at establishing a modified generic scoring system that is applicable to broad spectrum of rodent models.The histopathology of NAFLD was analyzed in several different mouse models of NAFLD to define generic criteria for histological assessment (preclinical scoring system. For validation of this scoring system, 36 slides of mouse livers, covering the whole spectrum of NAFLD, were blindly analyzed by ten observers. Additionally, the livers were blindly scored by one observer during two separate assessments longer than 3 months apart.The criteria macrovesicular steatosis, microvesicular steatosis, hepatocellular hypertrophy, inflammation and fibrosis were generally applicable to rodent NAFLD. The inter-observer reproducibility (evaluated using the Intraclass Correlation Coefficient between the ten observers was high for the analysis of macrovesicular steatosis and microvesicular steatosis (ICC = 0.784 and 0.776, all p<0.001, respectively and moderate for the analysis of hypertrophy and inflammation (ICC = 0.685 and 0.650, all p<0.001, respectively. The intra-observer reproducibility between the different observations of one observer was high for the analysis of macrovesicular steatosis, microvesicular steatosis and hypertrophy (ICC = 0.871, 0.871 and 0.896, all p<0.001, respectively and very high for the analysis of inflammation (ICC = 0.931, p

  6. Chemotherapy-Induced Depletion of OCT4-Positive Cancer Stem Cells in a Mouse Model of Malignant Testicular Cancer

    Timothy M. Pierpont

    2017-11-01

    Full Text Available Summary: Testicular germ cell tumors (TGCTs are among the most responsive solid cancers to conventional chemotherapy. To elucidate the underlying mechanisms, we developed a mouse TGCT model featuring germ cell-specific Kras activation and Pten inactivation. The resulting mice developed malignant, metastatic TGCTs composed of teratoma and embryonal carcinoma, the latter of which exhibited stem cell characteristics, including expression of the pluripotency factor OCT4. Consistent with epidemiological data linking human testicular cancer risk to in utero exposures, embryonic germ cells were susceptible to malignant transformation, whereas adult germ cells underwent apoptosis in response to the same oncogenic events. Treatment of tumor-bearing mice with genotoxic chemotherapy not only prolonged survival and reduced tumor size but also selectively eliminated the OCT4-positive cancer stem cells. We conclude that the chemosensitivity of TGCTs derives from the sensitivity of their cancer stem cells to DNA-damaging chemotherapy. : Using a mouse testicular germ cell tumor model, Pierpont et al. establish that male germ cells are susceptible to malignant transformation during a restricted window of embryonic development. The cancer stem cells of the resulting testicular cancers demonstrate genotoxin hypersensitivity, rendering these malignancies highly responsive to conventional chemotherapy. Keywords: testicular germ cell tumor, TGCT, cancer stem cells, CSCs, chemotherapy, embryonal carcinoma, EC, DNA damage response, DDR

  7. Developing a Screening Model to Establish Human Risk from Glacial Meltwater Release of Legacy Organochlorine Pollutants at the Silvretta Glacier in the Swiss Alps

    Miner, K. R.

    2017-12-01

    Organochlorine pollutants (OCPs) banned globally by the Stockholm Convention in 2004 are reemerging from melting glaciers in numerous alpine ecosystems. Despite the known OCP influx from glaciers, a study of human risk from uptake of pesticides in glacial meltwater has never been attempted. Our study qualifies human uptake routes and quantifies risk utilizing published meltwater data from the Silvretta Glacier in the Swiss Alps in combination with methodology established by the US Environmental Protection Agency (EPA). Relatively high concentrations of OCPs in Silvretta glacier meltwater reflect proximity to use near high density populations and provide the best estimate of a 95th percentile human risk scenario. This screening level model assesses direct PCB risk to humans through consumption of fish tissue and meltwater. Our model shows a risk for both cancer and non-cancer disease impacts to children with lifetime exposure to glacial meltwater and an average local fish consumption. For adults with an abbreviated 30 year exposure timeframe, the risk for non-cancer effects is negligible and cancer effects are only barely above screening level. Populations that consume higher quantities of local fish are at greater risk, with additional challenges borne by children. Further direct study into the individual level risk to Swiss residents from glacial meltwater pollution is deemed necessary by our screening study.

  8. Establishing the long-term fuel management scheme using point reactivity model

    Park, Yong-Soo; Kim, Jae-Hak; Lee, Young-Ouk; Song, Jae-Woong; Zee, Sung-Kyun

    1994-01-01

    A new approach to establish the long-term fuel management scheme is presented in this paper. The point reactivity model is used to predict the core average reactivity. An attempt to calculate batchwise power fraction is introduced through the two-dimensional nodal power algorithm based on the modified one-group diffusion equation and the number of fuel assemblies on the core periphery. Suggested is an empirical formula to estimate the radial leakage reactivity with ripe core design experience reflected. This approach predicts the cycle lengths and the discharge burnups of individual fuel batches up to an equilibrium core when the proper input data such as batch enrichment, batch size, type and content of burnable poison and reloading strategies are given. Eight benchmark calculations demonstrate that the new approach used in this study is reasonably accurate and highly efficient for the purpose of scoping calculation when compared with design code predictions. (author)

  9. Establishment of a rat model of portal vein ligation combined with in situ splitting.

    Libin Yao

    Full Text Available BACKGROUND: Portal vein ligation (PVL combined with in situ splitting (ISS has been shown to induce remarkable liver regeneration in patients. The purpose of this study was to establish a model of PVL+ISS in rats for exploring the possible mechanisms of liver regeneration using these techniques. MATERIALS AND METHODS: Rats were randomly assigned to three experimental groups: selective PVL, selective PVL+ISS and sham operation. The hepatic regeneration rate (HRR, Ki-67, liver biochemical determinations and histopathology were assessed at 24, 48, and 72 h and 7 days after the operation. The microcirculation of the median lobes before and after ISS was examined by laser speckle contrast imaging. Meanwhile, cytokines such as TNF-α, IL-6, HGF and HSP70 in regenerating liver lobes at 24 h was investigated by RT-PCR and ELISA. RESULTS: The HRR of PVL+ISS was much higher than that of the PVL at 72 h and 7 days after surgery (p<0.01. The expression of Ki-67 in hepatocytes in the regenerating liver lobe was stronger in the PVL+ISS group than in the PVL group at 48 and 72 h (p<0.01. There was a significant reduction in microcirculation blood perfusion of the left median lobe before and after ISS. Liver biochemical determinations and histopathology demonstrated more severe hepatocyte injury in the PVL+ISS group. Both the mRNA levels of TNF-α and IL-6 and the protein levels of TNF-α, IL-6 and HGF in regenerating liver lobes were higher in the PVL+ISS than the PVL alone. CONCLUSIONS: The higher HRR in the PVL+ISS compared with the PVL confirmed that we had successfully established a PVL+ISS model in rats. The possible mechanisms included the reduced microcirculation blood perfusion of the left median lobe and up-regulation of cytokines in the regenerating lobes after ISS.

  10. [Establishment of the Mathematical Model for PMI Estimation Using FTIR Spectroscopy and Data Mining Method].

    Wang, L; Qin, X C; Lin, H C; Deng, K F; Luo, Y W; Sun, Q R; Du, Q X; Wang, Z Y; Tuo, Y; Sun, J H

    2018-02-01

    To analyse the relationship between Fourier transform infrared (FTIR) spectrum of rat's spleen tissue and postmortem interval (PMI) for PMI estimation using FTIR spectroscopy combined with data mining method. Rats were sacrificed by cervical dislocation, and the cadavers were placed at 20 ℃. The FTIR spectrum data of rats' spleen tissues were taken and measured at different time points. After pretreatment, the data was analysed by data mining method. The absorption peak intensity of rat's spleen tissue spectrum changed with the PMI, while the absorption peak position was unchanged. The results of principal component analysis (PCA) showed that the cumulative contribution rate of the first three principal components was 96%. There was an obvious clustering tendency for the spectrum sample at each time point. The methods of partial least squares discriminant analysis (PLS-DA) and support vector machine classification (SVMC) effectively divided the spectrum samples with different PMI into four categories (0-24 h, 48-72 h, 96-120 h and 144-168 h). The determination coefficient ( R ²) of the PMI estimation model established by PLS regression analysis was 0.96, and the root mean square error of calibration (RMSEC) and root mean square error of cross validation (RMSECV) were 9.90 h and 11.39 h respectively. In prediction set, the R ² was 0.97, and the root mean square error of prediction (RMSEP) was 10.49 h. The FTIR spectrum of the rat's spleen tissue can be effectively analyzed qualitatively and quantitatively by the combination of FTIR spectroscopy and data mining method, and the classification and PLS regression models can be established for PMI estimation. Copyright© by the Editorial Department of Journal of Forensic Medicine.

  11. Establishment of a cervical cancer bio-bank for the Chinese population: from project-based sample collection to routine management.

    Yang, Ru; Li, Xiong; Zhou, Hang; Jia, Yao; Zhou, Jin; Huang, Kecheng; Tang, Fangxu; Hu, Ting; Shen, Jian; Chen, Zhilan; Wang, Shaoshuai; Sun, Haiying; Guo, Lili; Wang, Lin; Wang, Hui; Ma, Ding; Li, Shuang

    2015-08-01

    There is an increasing need for the establishment of a cervical cancer bio-bank that will facilitate both clinical and basic research. The cervical cancer bio-bank was first established in January 1999 and included two stages. First, a GWAS-based sample collection was conducted with special emphasis on the diagnosis and the retrieval of the corresponding bio-specimens, especially blood samples. Second, clinical data and their corresponding bio-specimens were routinely collected and handled. Notably, these bio-specimens also included samples from Wufeng Tujia Autonomous County, which has the highest incidence of cervical cancer in China. The specimens were collected from patients with cervical cancer and those with cervical intraepithelial neoplasia, while the control samples were collected from normal individuals. With special emphasis on clinical data and blood samples for the GWAS analysis, the collection of other bio-specimens was slow, and the pairing of specimens and clinical data was poor during the first stage. However, in the second stage, the pairing of the clinical data and its corresponding bio-specimens improved. At present, the samples procured and preserved in the bio-bank cover most regions of China and different ethnic groups for both the normal controls and cervical cancer patients of different pathological categories. This bio-bank of cervical cancer specimens from the Chinese population will greatly promote the studies of cervical cancer in China.

  12. Establishment and cell cycle distribution pattern of a radioresistant subline from human lung cancer D6 cell line

    Wei Qichun; Zheng Shu

    2003-01-01

    Objective: To establish a radioresistant cell subline from a human D6 lung cancer cell line and investigate the mechanism of radioresistance. Methods: D6 human NSCLC cells were exposed to X-rays generated by a linear accelerator(650 cGy per fraction). After a total exposure dose of 5200 cGy, a monoclone was obtained. The radiosensitivity and cell cycle distribution of this clone, together with its parent D6 cells, were measured by clonogenic assay and flow cytometry. Results: The new clone, namely D 6 -R subline, had a higher D 0 (D 0 =2.08 Gy) and a broader initial shoulder(Dq=1.64 Gy, N=2.20) than those of the parent D6 cell line (D 0 =1.84 Gy, Dq=0.34 Gy, N=1.20), being 1.65-fold increase in radioresistance as regards to the SF 2 . The D6-R subline also showed higher percentage of cells in S phase(53.4% vs 37.8%), but lower percentages in G 1 (44.1% vs 57.2%) and G 2 /M(2.5% vs 5%) phases. Conclusion: The new subline D6-R is more radioresistant as compare to its parent D6 cell line, and has a different cell cycle distribution

  13. Establishment, characterization, chemosensitivity, and radiosensitivity of two different cell lines derived from a human breast cancer biopsy

    Gioanni, J.; Courdi, A.; Lalanne, C.M.; Fischel, J.L.; Zanghellini, E.; Lambert, J.C.; Ettore, F.; Namer, M.

    1985-01-01

    In vitro culture of a human breast cancer biopsy fragment gave rise to two permanent cell lines, CAL 18 A and CAL 18 B, which were differentiated by both morphological and ultrastructural analysis. The karyotypic and growth properties of these two cell lines also differed, providing further evidence of cell heterogeneity within a given tumor. Both cell lines lost their hormone receptors in vitro. CAL 18 A cells grew in agar and were tumorigenic after inoculation into nude mice; neither of these properties was observed in CAL 18 B cells. The chemosensitivity of 12 antineoplastic drugs was assessed by a short-term assay, using inhibition of tritiated thymidine incorporation by the cells after contact with the drugs as the end point. Only a few drugs were active at moderate concentrations. The overall responses of both cell lines were similar. The cell survival curves, established by the colony method following a single dose of radiation, were also very similar, despite the greater heterogeneity of CAL 18 B cells. The two cell lines appear to be interrelated, since CAL 18 B cells were occasionally observed to emerge from CAL 18 A clones, suggesting that malignant cell redifferentiation may occur spontaneously in vitro

  14. The establishment of a multiple sclerosis model for clinical MRI study

    Zhang Haiqin; Li Kuncheng; Yu Chunshui; Ma Jia; Qin Wen; Ji Zhijuan; Piao Yueshan

    2009-01-01

    Objective: To establish a rat model of multiple sclerosis (MS) for clinical MRI study. Methods: The Lewis (LEW) rats were immunized by myelin oligodendrocyte glycoprotein peptide 35-55 (MOG 35-55 ) emulsified with complete Freunds adjuvant/incomplete Freunds adjuvant. Twenty LEW rats were selected. Group A rats were 5, group B rats were 10 and control group rats were 5. MRI and histopathology analysis were observed on group A and control group, and clinical course were observed on group B. The clinical course was observed and the brain and spinal cord of EAE rats were scanned on 3.0 T MR system with quadrature wrist joint coil on the third day of the acute stage of disease. The T 2 /T 1 weighted images and Gadolinium enhanced T 1 weighted images in 3D volume were obtained respectively. The magnetization transfer ratio (MTR) images were calculated with special software in workstation. Rats were sacrificed within 24 h after MRI, and the histopathological changes of central nervous system were observed. Results: Twice immunization of MOG 35-55 was used and a rat model of MS was successfully induced with all the rats. The model had varied clinical symptoms. The lesions of central nervous system at acute stage on group A (5 rats) were depicted on MRI. The lesions located in the brain and the spinal cord with main manifestation of hyperintensity on T 2 weighed images and hypointensity on T 1 weighted images. Some lesions had Gd-DTPA enhancement, and the value of MTR decreased. The infiltration of mononuclear cells around blood vessels and the extensive distribution of lesions of demyelination in brain and spinal cord were verified by histological examination. Conclusions: Twice immunization of MOG 35-55 could produce a rat model which mimics MS. The model is stable with higher incidence, and the antigen is cheap and obtained easily. The intravital monitoring of brain and spinal cord lesions in MOG 35-55 induced rat model is possible on 3.0 T clinical whole- body MR

  15. [The replacement therapy of rPTH(1-84) in established rat model of hypothyroidism].

    Ding, Zhiwei; Li, Tiancheng; Liu, Yuhe; Xiao, Shuifang

    2015-12-01

    To investigate the replacement therapy of rPTH(1-84) (recombinant human parathyroid hormone (1-84)) to hypothyroidism in established rat model. Rat model of hypothyroidism was established by resecting parathyroids. A total of 30 rats with removal of parathyroids were divided into 6 groups randomly, 5 in each group, and applied respectively with saline injection (negative control group), calcitriol treatment (positive control group) and quadripartite PTH administration with dose of 20, 40, 80 and 160 µg/kg (experimental groups). Saline and rPTH(1-84) were injected subcutaneously daily. Calcitriol was gavaged once a day. Sham-operation was conducted in 5 rats of negative control group. To verify the authenticity of the rat model with hypothyroidism, the serum was insolated centrifugally from rat blood that was obtained from angular vein at specific time to measure calcium and phosphorus concentration. Urine in 12 hours was collected by metabolic cages and the calcium concentration was measured. After 10-week drug treatment, the experiment was terminated and bilateral femoral bone and L2-5 lumbar vertebra were removed from rats. Bone mineral density (BMD)of bilateral femoral bone and lumbar vertebra was analyzed by dual X-ray absorptiometry (DXA). The concentration of bone alkaline phosphatase (BALP) in serum was determined by radioimmunoassay. The rat model with hypothyroidism was obtained by excising parathyroid gland and was verified by monitoring calcium and phosphorus concentration subsequently. Administration of rPTH(1-84) in the dose of 80 or 160 µg/kg made serum calcium and phosphorus back to normal levels, with no significant difference between the doses (P>0.05). The BMD in each group of rats with rPTH(1-84) administration was increased significantly (P0.05). Calcium and phosphorus return to normal level by administration of rPTH(1-84) in the dose of 80 µg/kg or 160 µg/kg, with increase in BMD. Calcitriol can return the level of calcium to normal and

  16. Mouse Models of Breast Cancer: Platforms for Discovering Precision Imaging Diagnostics and Future Cancer Medicine.

    Manning, H Charles; Buck, Jason R; Cook, Rebecca S

    2016-02-01

    Representing an enormous health care and socioeconomic challenge, breast cancer is the second most common cancer in the world and the second most common cause of cancer-related death. Although many of the challenges associated with preventing, treating, and ultimately curing breast cancer are addressable in the laboratory, successful translation of groundbreaking research to clinical populations remains an important barrier. Particularly when compared with research on other types of solid tumors, breast cancer research is hampered by a lack of tractable in vivo model systems that accurately recapitulate the relevant clinical features of the disease. A primary objective of this article was to provide a generalizable overview of the types of in vivo model systems, with an emphasis primarily on murine models, that are widely deployed in preclinical breast cancer research. Major opportunities to advance precision cancer medicine facilitated by molecular imaging of preclinical breast cancer models are discussed. © 2016 by the Society of Nuclear Medicine and Molecular Imaging, Inc.

  17. Establishment of a reversible model of prehepatic portal hypertension in rats.

    Zhao, Xin; Dou, Jian; Gao, Qing-Jun

    2016-08-01

    The aim of the present study was to improve upon the traditional model of pre-hepatic portal hypertension in rats, and simulate the anhepatic phase of orthotopic liver transplantation without veno-venous bypass. A reversible model of portal hypertension was induced by portal vein ligation, with a label ring ligated along the portal vein. A total of 135 male Wistar rats were divided into three groups: i) Normal control (NC) group; ii) portal hypertensive control (PHTC) group; and iii) reperfusion (R) group. In the R group, rats with portal hypertension underwent simultaneous clamping of the portal triad and retrohepatic vena cava for 1 h, followed by removal of the clamps to enable blood reperfusion. Portal venography and portal vein pressure were recorded during the surgery. Arterial oxygen pressure (PaO 2 ), and alanine aminotransferase (ALT), aspartate aminotransferase (AST) and total bilirubin (TBil) levels were determined, and pathological changes of the liver were investigated by immunohistochemical staining. The results demonstrated that, 3 weeks after portal vein ligation, the vein area and the free portal pressures in the PHTC group were significantly increased compared with those in the NC group. The serum ALT and AST levels in the R group at different time points were significantly elevated compared with those in the PHTC group, and reached their maximal levels at 24 h after reperfusion. Furthermore, the PaO 2 at 24 h after reperfusion was significantly decreased. In conclusion, the reversible model of pre-hepatic portal hypertension in rats was successfully established using the introduction of a label ring. This model may be useful for basic research focusing on the anhepatic phase of orthotopic liver transplantation without veno-venous bypass.

  18. Establishment of virtual three-dimensional model for intravascular interventional devices and its clinical value

    Wei Xin; Zhong Liming; Xie Xiaodong; Wang Chaohua; You Jian; Hu Hong; Hu Kongqiong; Zhao Xiaowei

    2012-01-01

    Objective: To explore virtual three-dimensional (3D) model for intravascular interventional devices,the method of preoperative simulation and its value in clinical work. Methods: The virtual models including catheter, guide wire, stent and coil were established by using the 3D moulding software of 3D Studio MAX R3. The interventional preoperative simulation was performed on personal computer including 21 patients of cerebral aneurysm embolization (anterior communicating artery 5, posterior communicating artery 10,middle cerebral artery 3, internal carotid artery 2, and vertebral artery 1), during interventional procedures, the surgeon relied on the simulation results for plastic micro-guide wire, catheter and the release of micro-coils and stents. Results: (1) All the virtual instruments and real instruments had similar shape,the overall tine for constructing virtual model was about 20 hours. The preoperative simulation took 50 to 80 minutes. (2) The simulation result of catheter insertion in the 18 cases had relevant value to guide micro-catheter, molding micro-guide wire tip, and shortened the operating time. For embolization, the simulation results of filling coil and releasing stent were similar to surgical results in 76% of the patients (16/21). (3)For teaching and training, 93% (38/41) of doctors in training believed that preoperative simulation facilitated the understanding of surgery. Conclusions: The method of virtual model of intravascular interventional devices was reliable. The preoperative simulation results could be used to guide practical clinical operation with relatively high degree of similarity, and could play a role in promoting researches on interventional virtual operations. (authors)

  19. Establishment of a mouse model with misregulated chromosome condensation due to defective Mcph1 function.

    Marc Trimborn

    Full Text Available Mutations in the human gene MCPH1 cause primary microcephaly associated with a unique cellular phenotype with premature chromosome condensation (PCC in early G2 phase and delayed decondensation post-mitosis (PCC syndrome. The gene encodes the BRCT-domain containing protein microcephalin/BRIT1. Apart from its role in the regulation of chromosome condensation, the protein is involved in the cellular response to DNA damage. We report here on the first mouse model of impaired Mcph1-function. The model was established based on an embryonic stem cell line from BayGenomics (RR0608 containing a gene trap in intron 12 of the Mcph1 gene deleting the C-terminal BRCT-domain of the protein. Although residual wild type allele can be detected by quantitative real-time PCR cell cultures generated from mouse tissues bearing the homozygous gene trap mutation display the cellular phenotype of misregulated chromosome condensation that is characteristic for the human disorder, confirming defective Mcph1 function due to the gene trap mutation. While surprisingly the DNA damage response (formation of repair foci, chromosomal breakage, and G2/M checkpoint function after irradiation appears to be largely normal in cell cultures derived from Mcph1(gt/gt mice, the overall survival rates of the Mcph1(gt/gt animals are significantly reduced compared to wild type and heterozygous mice. However, we could not detect clear signs of premature malignant disease development due to the perturbed Mcph1 function. Moreover, the animals show no obvious physical phenotype and no reduced fertility. Body and brain size are within the range of wild type controls. Gene expression on RNA and protein level did not reveal any specific pattern of differentially regulated genes. To the best of our knowledge this represents the first mammalian transgenic model displaying a defect in mitotic chromosome condensation and is also the first mouse model for impaired Mcph1-function.

  20. Laparoscopic training model using fresh human cadavers without the establishment of penumoperitoneum

    Ernesto Sasaki Imakuma

    2016-01-01

    Full Text Available Background: Laparoscopy is a well-established alternative to open surgery for treating many diseases. Although laparoscopy has many advantages, it is also associated with disadvantages, such as slow learning curves and prolonged operation time. Fresh frozen cadavers may be an interesting resource for laparoscopic training, and many institutions have access to cadavers. One of the main obstacles for the use of cadavers as a training model is the difficulty in introducing a sufficient pneumoperitoneum to distend the abdominal wall and provide a proper working space. The purpose of this study was to describe a fresh human cadaver model for laparoscopic training without requiring a pneumoperitoneum. Materials and Methods and Results: A fake abdominal wall device was developed to allow for laparoscopic training without requiring a pneumoperitoneum in cadavers. The device consists of a table-mounted retractor, two rail clamps, two independent frame arms, two adjustable handle and rotating features, and two frames of the abdominal wall. A handycam is fixed over a frame arm, positioned and connected through a USB connection to a television and dissector; scissors and other laparoscopic materials are positioned inside trocars. The laparoscopic procedure is thus simulated. Conclusion: Cadavers offer a very promising and useful model for laparoscopic training. We developed a fake abdominal wall device that solves the limitation of space when performing surgery on cadavers and removes the need to acquire more costly laparoscopic equipment. This model is easily accessible at institutions in developing countries, making it one of the most promising tools for teaching laparoscopy.

  1. Establishment of a mouse model with misregulated chromosome condensation due to defective Mcph1 function.

    Trimborn, Marc; Ghani, Mahdi; Walther, Diego J; Dopatka, Monika; Dutrannoy, Véronique; Busche, Andreas; Meyer, Franziska; Nowak, Stefanie; Nowak, Jean; Zabel, Claus; Klose, Joachim; Esquitino, Veronica; Garshasbi, Masoud; Kuss, Andreas W; Ropers, Hans-Hilger; Mueller, Susanne; Poehlmann, Charlotte; Gavvovidis, Ioannis; Schindler, Detlev; Sperling, Karl; Neitzel, Heidemarie

    2010-02-16

    Mutations in the human gene MCPH1 cause primary microcephaly associated with a unique cellular phenotype with premature chromosome condensation (PCC) in early G2 phase and delayed decondensation post-mitosis (PCC syndrome). The gene encodes the BRCT-domain containing protein microcephalin/BRIT1. Apart from its role in the regulation of chromosome condensation, the protein is involved in the cellular response to DNA damage. We report here on the first mouse model of impaired Mcph1-function. The model was established based on an embryonic stem cell line from BayGenomics (RR0608) containing a gene trap in intron 12 of the Mcph1 gene deleting the C-terminal BRCT-domain of the protein. Although residual wild type allele can be detected by quantitative real-time PCR cell cultures generated from mouse tissues bearing the homozygous gene trap mutation display the cellular phenotype of misregulated chromosome condensation that is characteristic for the human disorder, confirming defective Mcph1 function due to the gene trap mutation. While surprisingly the DNA damage response (formation of repair foci, chromosomal breakage, and G2/M checkpoint function after irradiation) appears to be largely normal in cell cultures derived from Mcph1(gt/gt) mice, the overall survival rates of the Mcph1(gt/gt) animals are significantly reduced compared to wild type and heterozygous mice. However, we could not detect clear signs of premature malignant disease development due to the perturbed Mcph1 function. Moreover, the animals show no obvious physical phenotype and no reduced fertility. Body and brain size are within the range of wild type controls. Gene expression on RNA and protein level did not reveal any specific pattern of differentially regulated genes. To the best of our knowledge this represents the first mammalian transgenic model displaying a defect in mitotic chromosome condensation and is also the first mouse model for impaired Mcph1-function.

  2. The establishment of MELCOR/SNAP model of Chinshan nuclear power plant for Ultimate Response Guideline

    Hsu, Wen-Sheng, E-mail: wshsu@ess.nthu.edu.tw [Nuclear Science and Technology Development Center, Institute of Nuclear Engineering and Science, National Tsing Hua University, Nuclear and New Energy Education and Research Foundation, No. 101, Section 2, Kuang Fu Rd., HsinChu 30013, Taiwan, ROC (China); Chiang, Yu, E-mail: s101013702@m101.nthu.edu.tw [Nuclear Science and Technology Development Center, Institute of Nuclear Engineering and Science, National Tsing Hua University, Nuclear and New Energy Education and Research Foundation, No. 101, Section 2, Kuang Fu Rd., HsinChu 30013, Taiwan, ROC (China); Wang, Jong-Rong, E-mail: jongrongwang@gmail.com [Nuclear Science and Technology Development Center, Institute of Nuclear Engineering and Science, National Tsing Hua University, Nuclear and New Energy Education and Research Foundation, No. 101, Section 2, Kuang Fu Rd., HsinChu 30013, Taiwan, ROC (China); Wang, Ting-Yi, E-mail: minired1119@gmail.com [Nuclear Science and Technology Development Center, Institute of Nuclear Engineering and Science, National Tsing Hua University, Nuclear and New Energy Education and Research Foundation, No. 101, Section 2, Kuang Fu Rd., HsinChu 30013, Taiwan, ROC (China); Wang, Te-Chuan, E-mail: tcwang@iner.gov.tw [Institute of Nuclear Energy Research Atomic Energy Council, R.O.C., 1000, Wenhua Road Jiaan Village, Longtan Township, Taoyuan County 32546, Taiwan (China); Teng, Jyh-Tong, E-mail: jyhtong@cycu.edu.tw [Department of Mechanical Engineering, Chung Yuan Christian University, 200, Chung Pei Rd, Chung Li 32023, Taiwan, ROC (China); Chen, Shao-Wen, E-mail: chensw@mx.nthu.edu.tw [Nuclear Science and Technology Development Center, Institute of Nuclear Engineering and Science, National Tsing Hua University, Nuclear and New Energy Education and Research Foundation, No. 101, Section 2, Kuang Fu Rd., HsinChu 30013, Taiwan, ROC (China); and others

    2017-01-15

    Highlights: • The establishment of a MELCOR/SNAP model of Chinshan (BWR/4). • MELCOR/SNAP model was used to estimate the effectiveness of URG for Chinshan. • The MELCOR results were compared to MAAP, TRACE and PCTRAN. • URG is a new method to prevent a Fukushima-like accident. • The low raw water (150 GPM) can make the cladding temperature below 1088.7 K. - Abstract: After Fukushima Daiichi disaster, the safety analysis of severe accidents became one of the safety concerns in Taiwan. The Emergency Operating Procedure (EOP) cannot cope with a multiple system failure situation under a severe accident since it is a “Symptom-basis” procedure. To deal with that, Taiwan Power Company built up a new strategy for Fukushima-like accident called Ultimate Response Guideline (URG). It is a simple strategy with three main conditions: loss of regular motor driven injection system, loss of all AC power and tsunami/earthquake warning. If two of three happen, the operating procedure will change from EOP to URG and start the main works by following the strategy. There are three main works in URG: controlled-depressurization, line up low pressure injection water and prepare containment venting. In this study, MELCOR2.1 was used to calculate the cases of URG and checked the goal of the strategy that prevents the accident or not. There were three steps in this research. First, a model of Chinshan nuclear power plant (NPP) was built. Second, one was the case with URG and the other was not by using the above MELCOR model. The results were compared to MAAP5.0, TRACE and PCTRAN. Finally, some sensitivity studies of depressurization and water injection rate were done.

  3. Establishment of a rat and guinea pig aortic interposition graft model reveals model-specific patterns of intimal hyperplasia.

    Gregory, Elaine K; Vercammen, Janet M; Flynn, Megan E; Kibbe, Melina R

    2016-12-01

    Although the aortic interposition bypass model has been widely used to evaluate biomaterials for bypass grafting, there is no comprehensive description of the procedure or of the distribution of intimal hyperplasia that results. The objectives of this study were to (1) review and summarize approaches of aortic interposition grafting in animal models, (2) determine the pertinent anatomy for this procedure, (3) validate this model in the rat and guinea pig, and (4) compare the distribution of intimal hyperplasia that develops in each species. A literature search was performed in PubMed from 1980 to the present to analyze the use of anesthesia, anticoagulation, antiplatelet agents, graft material, suture, and anastomotic techniques. Using 10-week-old male Sprague-Dawley rats and Hartley guinea pigs, we established pertinent aortic anatomy, developed comparable models, and assessed complications for each model. At 30 days, the graft and associated aorta were explanted, intimal formation was assessed morphometrically, and cellularity was assessed via nuclear counting. We reviewed 30 articles and summarized the pertinent procedural findings. Upon establishing both animal models, key anatomic differences between the species that affect this model were noted. Guinea pigs have a much larger cecum, increased retroperitoneal fat, and lack the iliolumbar vessels compared with the rat. Surgical outcomes for the rat model included a 53% technical success rate and a 32% technical error rate. Surgical outcomes for the guinea pig model included a 69% technical success rate and a 31% technical error rate. These two species demonstrated unique distribution of intimal hyperplasia at 30 days. Intimal hyperplasia in the rat model was greatest at two areas, the proximal graft (5400 μm 2 ; P guinea pig model developed similar intimal hyperplasia throughout the graft (4500-5100 μm 2 ; P guinea pig, and describe a unique distribution of intimal formation that results in both species

  4. Establishment of 9L/F344 rat intracerebral glioma model of brain tumor stem cells

    Zong-yu XIAO

    2015-04-01

    Full Text Available Objective To establish the 9L/F344 rat intracerebral glioma model of brain tumor stem cells.  Methods Rat 9L gliosarcoma stem-like cells were cultured in serum-free suspension. The expression of CD133 and nestin were tested by immunohistochemistry. A total of 48 inbredline male F344 rats were randomly divided into 2 groups, and 9L tumor sphere cells and 9L monolayer cells were respectively implanted into the right caudate nucleus of F344 rats in 2 groups. Survival time was observed and determined using the method of Kaplan-Meier survival analysis. Fourteen days after implantation or when the rats were dying, their brains were perfused and sectioned for HE staining, and CD133 and nestin were detected by immunohistochemistry.  Results Rat 9L tumor spheres were formed with suspension culture in serum-free medium. The gliomas formed in both groups were invasive without obvious capsule. More new vessels, bleeding and necrosis could be detected in 9L tumor spheres group. The tumor cells in both groups were positive for CD133 and nestin. There was no significant difference in the expression of CD133 and nestin between 2 groups (P > 0.05, for all. According to the expression of nestin, the tumors formed by 9L tumor sphere cells were more invasive. The median survival time of the rats bearing 9L tumor sphere cells was 15 d (95%CI: 15.219-15.781, and the median survival time of the rats bearing 9L monolayer cells was 21 d (95%CI: 20.395-21.605. There was significant difference between 2 groups (χ2 = 12.800, P = 0.000.  Conclusions 9L/F344 rat intracerebral glioma model of brain tumor stem cells is successfully established, which provides a glioma model for the future research. DOI: 10.3969/j.issn.1672-6731.2015.04.012

  5. Establish susceptibility and risk assessment models for rainfall-induced landslide: A case in Central Taiwan

    Wu, Chunhung; Huang, Jyuntai

    2017-04-01

    Most of the landslide cases in Taiwan were triggered by rainfall or earthquake events. The heavy rainfall in the typhoon seasons, from June to October, causes the landslide hazard more serious. Renai Towhship is of the most large landslide cases after 2009 Typhoon Morakot (from Aug. 5 to Aug. 10, 2009) in Taiwan. Around 2,744 landslides cases with the total landslide area of 21.5 km2 (landslide ratio =1.8%), including 26 large landslide cases, induced after 2009 Typhoon Morakot in Renai Towhship. The area of each large landslides case is more than 0.1 km2, and the area of the largest case is around 0.96 km2. 58% of large landslide cases locate in the area with metamorphosed sandstone. The mean slope of 26 large landslide cases ranges from 15 degree to 56 degree, and the accumulated rainfall during 2009 Typhoon Morakot ranges from 530 mm to 937 mm. Three methods, including frequency ratio method (abbreviated as FR), weights of evidence method (abbreviated as WOE), and logistic regression method (abbreviated as LR), are used in this study to establish the landslides susceptibility in the Renai Township, Nantou County, Taiwan. Eight landslide related-factors, including elevation, slope, aspect, geology, land use, distance to drainage, distance to fault, accumulation rainfall during 2009 Typhoon Morakot, are used to establish the landslide susceptibility models in this study. The landslide inventory after 2009 Typhoon Morakot is also used to test the model performance in this study. The mean accumulated rainfall in Renai Township during 2009 typhoon Morakot was around 735 mm with the maximum 1-hr, 3-hrs, and 6-hrs rainfall intensity of 44 mm/1-hr, 106 mm/3-hrs and 204 mm/6-hrs, respectively. The range of original susceptibility values established by three methods are 4.0 to 20.9 for FR, -33.8 to -16.1 for WOE, and -41.7 to 5.7 for LR, and the mean landslide susceptibility value are 8.0, -24.6 and 0.38, respectively. The AUC values are 0.815 for FR, 0.816 for WOE, and 0

  6. The Establishment of Metabolic Syndrome Model by Induction of Fructose Drinking Water in Male Wistar Rats

    Norshalizah Mamikutty

    2014-01-01

    Full Text Available Background. Metabolic syndrome can be caused by modification of diet by means of consumption of high carbohydrate and high fat diet such as fructose. Aims. To develop a metabolic syndrome rat model by induction of fructose drinking water (FDW in male Wistar rats. Methods. Eighteen male Wistar rats were fed with FDW 20% and FDW 25% for a duration of eight weeks. The physiological changes with regard to food and fluid intake, as well as calorie intake, were measured. The metabolic changes such as obesity, dyslipidaemia, hypertension, and hyperglycaemia were determined. Data was presented in mean ± SEM subjected to one-way ANOVA. Results. Male Wistar rats fed with FDW 20% for eight weeks developed significant higher obesity parameters compared to those fed with FDW 25%. There was hypertrophy of adipocytes in F20 and F25. There were also systolic hypertension, hypertriglyceridemia, and hyperglycemia in both groups. Conclusion. We conclude that the metabolic syndrome rat model is best established with the induction of FDW 20% for eight weeks. This was evident in the form of higher obesity parameter which caused the development of the metabolic syndrome.

  7. Establishment of quantitative severity evaluation model for spinal cord injury by metabolomic fingerprinting.

    Jin Peng

    Full Text Available Spinal cord injury (SCI is a devastating event with a limited hope for recovery and represents an enormous public health issue. It is crucial to understand the disturbances in the metabolic network after SCI to identify injury mechanisms and opportunities for treatment intervention. Through plasma 1H-nuclear magnetic resonance (NMR screening, we identified 15 metabolites that made up an "Eigen-metabolome" capable of distinguishing rats with severe SCI from healthy control rats. Forty enzymes regulated these 15 metabolites in the metabolic network. We also found that 16 metabolites regulated by 130 enzymes in the metabolic network impacted neurobehavioral recovery. Using the Eigen-metabolome, we established a linear discrimination model to cluster rats with severe and mild SCI and control rats into separate groups and identify the interactive relationships between metabolic biomarkers in the global metabolic network. We identified 10 clusters in the global metabolic network and defined them as distinct metabolic disturbance domains of SCI. Metabolic paths such as retinal, glycerophospholipid, arachidonic acid metabolism; NAD-NADPH conversion process, tyrosine metabolism, and cadaverine and putrescine metabolism were included. In summary, we presented a novel interdisciplinary method that integrates metabolomics and global metabolic network analysis to visualize metabolic network disturbances after SCI. Our study demonstrated the systems biological study paradigm that integration of 1H-NMR, metabolomics, and global metabolic network analysis is useful to visualize complex metabolic disturbances after severe SCI. Furthermore, our findings may provide a new quantitative injury severity evaluation model for clinical use.

  8. Establishment of a head injury by club model in rabbits and experimental conditions

    Cao Yunxing; Xi Huanjiu; Zhang Jing; Li Hongwei; Yin Zhiyong; Zhao Hui

    2013-01-01

    Objective: To establish an animal model to replicate the injury by club in forensic medicine. Methods: Twenty-four New Zealand white rabbits were divided into control group (n=4), minor injury group (n=10), and severe injury group (n=10). Based on the BIM-Ⅱ Horizontal Bio-impact Machine, a self-designed iron bar was used to produce head injury by club. Six hours after injury, all the rabbits were subjected to a CT examination and dissected to observe the injury morphology and undergo routine pathological examination. Four control, six minor and severe rabbits were given moisture content examination. Results: Varying degrees of positive signs of the nervous system were observed in all the injured rabbits within 6 hours. The mortality rate was 1/10 in the minor injury group and 6/10 in the severe injury group. The morphological changes consisted of different levels of scalp hematoma, skull fracture, epidural hematoma, subdural hematoma, subarachnoid hemorrhage and brain injury. The difference in moisture content between the three groups was of statistical significance. Conclusion: Under the rigidly-controlled experimental condition, this animal model produces good reproducibility and stable results. Meanwhile, it can simulate the morphology of injury by club and be used to study the mechanism of injury by club in forensic medicine. (authors)

  9. Establishment of a Radiation-Induced Fibrosis Model in BALB/c Mice

    Ryu, Seung Hee; Lee, Sang Wook; Moon, Soo Young; Oh, Jeong Yoon; Yang, Youn Joo; Park, Jin Hong [Dept. of Radiation Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul (Korea, Republic of)

    2010-11-15

    Although radiation-induced fibrosis is one of the common sequelae occurring after irradiation of skin and soft tissues, the treatment methods are not well standardized. This study aimed to establish the skin fibrosis mouse model by fractionated radiation for the further mechanism studies or testing the efficacy of therapeutic candidates. The right hind limbs of BALB/c mice received two fractions of 20 Gy using a therapeutic linear accelerator. Early skin damages were scored and tissue fibrosis was assessed by the measurement of a leg extension. Morphological changes were assessed by H and E staining and by Masson's Trichrome staining. TGF-{beta}1 expression from soft tissues was also detected by immunohistochemistry and PCR. Two fractions of 20 Gy irradiation were demonstrated as being enough to induce early skin damage effects such as erythema, mild skin dryness, dry and wet desquamation within several weeks of radiation. After 13 weeks of irradiation, the average radiation-induced leg contraction was 11.1 {+-} 6.2 mm. Morphologic changes in irradiated skin biopsies exhibited disorganized collagen and extracellular matrix fibers, as well as the accumulation of myofibroblasts compared to the non-irradiated skin. Moreover, TGF-{beta}1 expression in tissue was increased by radiation. These results show that two fractions of 20 Gy irradiation can induce skin fibrosis in BALB/c mice accompanied by other common characteristics of skin damages. This animal model can be a useful tool for studying skin fibrosis induced by radiation.

  10. The Establishment and Characteristics of Rat Model of Atherosclerosis Induced by Hyperuricemia

    Zhen Liu

    2016-01-01

    Full Text Available Epidemiological studies have identified hyperuricemia as an independent risk factor for cardiovascular disease. However, the mechanism whereby hyperuricemia causes atherosclerosis remains unclear. The objective of the study was to establish a new rat model of hyperuricemia-induced atherosclerosis. Wistar-Kyoto rats were randomly allocated to either a normal diet (ND, high-fat diet (HFD, or high-adenine diet (HAD, followed by sacrifice 4, 8, or 12 weeks later. Serum uric acid and lipid levels were analyzed, pathologic changes in the aorta were observed by hematoxylin and eosin staining, and mRNA expression was evaluated by quantitative real-time polymerase chain reaction. Serum uric acid and TC were significantly increased in the HAD group at 4 weeks compared with the ND group, but there was no significant difference in serum uric acid between the ND and HFD groups. Aorta calcification occurred earlier and was more severe in the HAD group, compared with the HFD group. Proliferating cell nuclear antigen, monocyte chemotactic factor-1, intercellular adhesion molecule-1, and vascular cell adhesion molecule-1 mRNA levels were increased in the HFD and HAD groups compared with the ND group. This new animal model will be a useful tool for investigating the mechanisms responsible for hyperuricemia-induced atherosclerosis.

  11. Organoid Models of Human and Mouse Ductal Pancreatic Cancer

    Boj, Sylvia F.; Hwang, Chang-Il; Baker, Lindsey A.; Chio, Iok In Christine; Engle, Dannielle D.; Corbo, Vincenzo; Jager, Myrthe; Ponz-Sarvise, Mariano; Tiriac, Hervé; Spector, Mona S.; Gracanin, Ana; Oni, Tobiloba; Yu, Kenneth H.; van Boxtel, Ruben; Huch, Meritxell; Rivera, Keith D.; Wilson, John P.; Feigin, Michael E.; Öhlund, Daniel; Handly-Santana, Abram; Ardito-Abraham, Christine M.; Ludwig, Michael; Elyada, Ela; Alagesan, Brinda; Biffi, Giulia; Yordanov, Georgi N.; Delcuze, Bethany; Creighton, Brianna; Wright, Kevin; Park, Youngkyu; Morsink, Folkert H.M.; Molenaar, I. Quintus; Borel Rinkes, Inne H.; Cuppen, Edwin; Hao, Yuan; Jin, Ying; Nijman, Isaac J.; Iacobuzio-Donahue, Christine; Leach, Steven D.; Pappin, Darryl J.; Hammell, Molly; Klimstra, David S.; Basturk, Olca; Hruban, Ralph H.; Offerhaus, George Johan; Vries, Robert G.J.; Clevers, Hans; Tuveson, David A.

    2015-01-01

    SUMMARY Pancreatic cancer is one of the most lethal malignancies due to its late diagnosis and limited response to treatment. Tractable methods to identify and interrogate pathways involved in pancreatic tumorigenesis are urgently needed. We established organoid models from normal and neoplastic murine and human pancreas tissues. Pancreatic organoids can be rapidly generated from resected tumors and biopsies, survive cryopreservation and exhibit ductal- and disease stage-specific characteristics. Orthotopically transplanted neoplastic organoids recapitulate the full spectrum of tumor development by forming early-grade neoplasms that progress to locally invasive and metastatic carcinomas. Due to their ability to be genetically manipulated, organoids are a platform to probe genetic cooperation. Comprehensive transcriptional and proteomic analyses of murine pancreatic organoids revealed genes and pathways altered during disease progression. The confirmation of many of these protein changes in human tissues demonstrates that organoids are a facile model system to discover characteristics of this deadly malignancy. PMID:25557080

  12. Risk prediction models for selection of lung cancer screening candidates: A retrospective validation study

    K. ten Haaf (Kevin); J. Jeon (Jihyoun); M.C. Tammemagi (Martin); S.S. Han (Summer); C.Y. Kong (Chung Yin); S.K. Plevritis (Sylvia); E. Feuer (Eric); H.J. de Koning (Harry); E.W. Steyerberg (Ewout W.); R. Meza (Rafael)

    2017-01-01

    textabstractBackground: Selection of candidates for lung cancer screening based on individual risk has been proposed as an alternative to criteria based on age and cumulative smoking exposure (pack-years). Nine previously established risk models were assessed for their ability to identify those most

  13. Modeling of skin cancer dermatoscopy images

    Iralieva, Malica B.; Myakinin, Oleg O.; Bratchenko, Ivan A.; Zakharov, Valery P.

    2018-04-01

    An early identified cancer is more likely to effective respond to treatment and has a less expensive treatment as well. Dermatoscopy is one of general diagnostic techniques for skin cancer early detection that allows us in vivo evaluation of colors and microstructures on skin lesions. Digital phantoms with known properties are required during new instrument developing to compare sample's features with data from the instrument. An algorithm for image modeling of skin cancer is proposed in the paper. Steps of the algorithm include setting shape, texture generation, adding texture and normal skin background setting. The Gaussian represents the shape, and then the texture generation based on a fractal noise algorithm is responsible for spatial chromophores distributions, while the colormap applied to the values corresponds to spectral properties. Finally, a normal skin image simulated by mixed Monte Carlo method using a special online tool is added as a background. Varying of Asymmetry, Borders, Colors and Diameter settings is shown to be fully matched to the ABCD clinical recognition algorithm. The asymmetry is specified by setting different standard deviation values of Gaussian in different parts of image. The noise amplitude is increased to set the irregular borders score. Standard deviation is changed to determine size of the lesion. Colors are set by colormap changing. The algorithm for simulating different structural elements is required to match with others recognition algorithms.

  14. Establishment of a murine graft-versus-myeloma model using allogeneic stem cell transplantation.

    Marilène Binsfeld

    Full Text Available Multiple myeloma (MM is a malignant plasma cell disorder with poor long-term survival and high recurrence rates. Despite evidence of graft-versus-myeloma (GvM effects, the use of allogeneic hematopoietic stem cell transplantation (allo-SCT remains controversial in MM. In the current study, we investigated the anti-myeloma effects of allo-SCT from B10.D2 mice into MHC-matched myeloma-bearing Balb/cJ mice, with concomitant development of chronic graft-versus-host disease (GvHD.Balb/cJ mice were injected intravenously with luciferase-transfected MOPC315.BM cells, and received an allogeneic (B10.D2 donor or autologous (Balb/cJ donor transplant 30 days later. We observed a GvM effect in 94% of the allogeneic transplanted mice, as the luciferase signal completely disappeared after transplantation, whereas all the autologous transplanted mice showed myeloma progression. Lower serum paraprotein levels and lower myeloma infiltration in bone marrow and spleen in the allogeneic setting confirmed the observed GvM effect. In addition, the treated mice also displayed chronic GvHD symptoms. In vivo and in vitro data suggested the involvement of effector memory CD4 and CD8 T cells associated with the GvM response. The essential role of CD8 T cells was demonstrated in vivo where CD8 T-cell depletion of the graft resulted in reduced GvM effects. Finally, TCR Vβ spectratyping analysis identified Vβ families within CD4 and CD8 T cells, which were associated with both GvM effects and GvHD, whereas other Vβ families within CD4 T cells were associated exclusively with either GvM or GvHD responses.We successfully established an immunocompetent murine model of graft-versus-myeloma. This is the first murine GvM model using immunocompetent mice that develop MM which closely resembles human MM disease and that are treated after disease establishment with an allo-SCT. Importantly, using TCR Vβ spectratyping, we also demonstrated the presence of GvM unique responses

  15. Study on establishment and mechanics application of finite element model of bovine eye.

    Cui, Yan-Hui; Huang, Ju-Fang; Cheng, Si-Ying; Wei, Wei; Shang, Lei; Li, Na; Xiong, Kun

    2015-08-13

    Glaucoma mainly induced by increased intraocular pressure (IOP), it was believed that the pressure that wall of eyeball withstands were determined by material properties of the tissue and stereoscopic geometry of the eyeball. In order to study the pressure changes in different parts of interior eyeball wall, it is necessary to develop a novel eye ball FEM with more accurate geometry and material properties. Use this model to study the stress changes in different parts of eyeball, especially the lamina cribrosa (LC) under normal physiological and pathological IOP, and provide a mathematical model for biomechanical studies of selected retinal ganglion cells (RGCs) death. (1) Sclera was cut into 3.8-mm wide, 14.5-mm long strips, and cornea was cut into 9.5-mm-wide and 10-mm-long strips; (2) 858 Mini BionixII biomechanical loading instrument was used to stretch sclera and cornea. The stretching rate for sclera was 0.3 mm/s, 3 mm/s, 30 mm/s, 300 mm/s; and for cornea were 0.3 mm/s and 30 mm/s. The deformation-stress curve was recorded; (3) Naso-temporal and longitudinal distance of LC were measured; (4) Micro-CT was used to accurately scan fresh bovine eyes and obtain the geometrical image and data to establish bovine eye model. 3-D reconstruction was performed using these images and data to work out the geometric shape of bovine eye; (5) IOP levels for eyeball FEM was set and the inner wall of eyeball was used taken as load-bearing part. Simulated eyeball FE modeling was run under the IOP level of 10 mmHg, 30 mmHg, 60 mmHg and 100 mmHg, and the force condition of different parts of eyeball was recorded under different IOP levels. (1) We obtained the material parameters more in line with physiological conditions and established a more realistic eyeball model using reversed engineering of parameters optimization method to calculate the complex nonlinear super-elastic and viscoelastic parameters more accurately; (2) We observed the following phenomenon by

  16. Modeling Cervical Cancer Prevention in Developed Countries

    Kim, Jane J.; Brisson, Marc; Edmunds, W. John; Goldie, Sue J.

    2009-01-01

    Cytology-based screening has reduced cervical cancer mortality in countries able to implement, sustain and financially support organized programs that achieve broad coverage. These ongoing secondary prevention efforts considerably complicate the question of whether vaccination against Human Papillomavirus (HPV) types -16 and 18 should be introduced. Policy questions focus primarily on the target ages of vaccination, appropriate ages for a temporary “catch-up” program, possible revisions in screening policies to optimize synergies with vaccination, including the increased used of HPV DNA testing, and the inclusion of boys in the vaccination program. Decision-analytic models are increasingly being developed to simulate disease burden and interventions in different settings in order to evaluate the benefits and cost-effectiveness of primary and secondary interventions for informed decision-making. This article is a focused review on existing mathematical models that have been used to evaluate HPV vaccination in the context of developed countries with existing screening programs. Despite variations in model assumptions and uncertainty in existing data, pre-adolescent vaccination of girls is consistently found to be attractive in the context of current screening practices, provided there is complete and lifelong vaccine protection and widespread vaccination coverage. Questions related to catch-up vaccination programs, potential benefits of other non-cervical cancer outcomes and inclusion of boys are subject to far more uncertainty, and results from these analyses have reached conflicting conclusions. Most analyses find that some catch-up vaccination is warranted but becomes increasingly unattractive as the catch-up age is extended, and vaccination of boys is unlikely to be cost-effective if reasonable levels of coverage are achieved in girls or coverage among girls can be improved. The objective of the review is to highlight points of consensus and qualitative

  17. The thyroid cancer policy model: A mathematical simulation model of papillary thyroid carcinoma in The U.S. population.

    Carrie Lubitz

    Full Text Available Thyroid cancer affects over ½ million people in the U.S. and the incidence of thyroid cancer has increased worldwide at a rate higher than any other cancer, while survival has remained largely unchanged. The aim of this research was to develop, calibrate and verify a mathematical disease model to simulate the natural history of papillary thyroid cancer, which will serve as a platform to assess the effectiveness of clinical and cancer control interventions.Herein, we modeled the natural pre-clinical course of both benign and malignant thyroid nodules with biologically relevant health states from normal to detected nodule. Using established calibration techniques, optimal parameter sets for tumor growth characteristics, development rate, and detection rate were used to fit Surveillance Epidemiology and End Results (SEER incidence data and other calibration targets.Model outputs compared to calibration targets demonstrating sufficient calibration fit and model validation are presented including primary targets of SEER incidence data and size distribution at detection of malignancy. Additionally, we show the predicted underlying benign and malignant prevalence of nodules in the population, the probability of detection based on size of nodule, and estimates of growth over time in both benign and malignant nodules.This comprehensive model provides a dynamic platform employable for future comparative effectiveness research. Future model analyses will test and assess various clinical management strategies to improve patient outcomes related to thyroid cancer and optimize resource utilization for patients with thyroid nodules.

  18. Database supported electronic retrospective analyses in radiation oncology. Establishing a workflow using the example of pancreatic cancer

    Kessel, K.A.; Habermehl, D.; Bougatf, N.; Debus, J.; Combs, S.E.; Jaeger, A.; Floca, R.O.; Zhang, L.; Bendl, R.

    2012-01-01

    Purpose: Especially in the field of radiation oncology, handling a large variety of voluminous datasets from various information systems in different documentation styles efficiently is crucial for patient care and research. To date, conducting retrospective clinical analyses is rather difficult and time consuming. With the example of patients with pancreatic cancer treated with radio-chemotherapy, we performed a therapy evaluation by using an analysis system connected with a documentation system. Materials and methods: A total number of 783 patients have been documented into a professional, database-based documentation system. Information about radiation therapy, diagnostic images and dose distributions have been imported into the web-based system. Results: For 36 patients with disease progression after neoadjuvant chemoradiation, we designed and established an analysis workflow. After an automatic registration of the radiation plans with the follow-up images, the recurrence volumes are segmented manually. Based on these volumes the DVH (dose volume histogram) statistic is calculated, followed by the determination of the dose applied to the region of recurrence. All results are saved in the database and included in statistical calculations. Conclusion: The main goal of using an automatic analysis tool is to reduce time and effort conducting clinical analyses, especially with large patient groups. We showed a first approach and use of some existing tools, however manual interaction is still necessary. Further steps need to be taken to enhance automation. Already, it has become apparent that the benefits of digital data management and analysis lie in the central storage of data and reusability of the results. Therefore, we intend to adapt the analysis system to other types of tumors in radiation oncology. (orig.)

  19. Serum and urine metabolomics study reveals a distinct diagnostic model for cancer cachexia

    Yang, Quan‐Jun; Zhao, Jiang‐Rong; Hao, Juan; Li, Bin; Huo, Yan; Han, Yong‐Long; Wan, Li‐Li; Li, Jie; Huang, Jinlu; Lu, Jin

    2017-01-01

    Abstract Background Cachexia is a multifactorial metabolic syndrome with high morbidity and mortality in patients with advanced cancer. The diagnosis of cancer cachexia depends on objective measures of clinical symptoms and a history of weight loss, which lag behind disease progression and have limited utility for the early diagnosis of cancer cachexia. In this study, we performed a nuclear magnetic resonance‐based metabolomics analysis to reveal the metabolic profile of cancer cachexia and establish a diagnostic model. Methods Eighty‐four cancer cachexia patients, 33 pre‐cachectic patients, 105 weight‐stable cancer patients, and 74 healthy controls were included in the training and validation sets. Comparative analysis was used to elucidate the distinct metabolites of cancer cachexia, while metabolic pathway analysis was employed to elucidate reprogramming pathways. Random forest, logistic regression, and receiver operating characteristic analyses were used to select and validate the biomarker metabolites and establish a diagnostic model. Results Forty‐six cancer cachexia patients, 22 pre‐cachectic patients, 68 weight‐stable cancer patients, and 48 healthy controls were included in the training set, and 38 cancer cachexia patients, 11 pre‐cachectic patients, 37 weight‐stable cancer patients, and 26 healthy controls were included in the validation set. All four groups were age‐matched and sex‐matched in the training set. Metabolomics analysis showed a clear separation of the four groups. Overall, 45 metabolites and 18 metabolic pathways were associated with cancer cachexia. Using random forest analysis, 15 of these metabolites were identified as highly discriminating between disease states. Logistic regression and receiver operating characteristic analyses were used to create a distinct diagnostic model with an area under the curve of 0.991 based on three metabolites. The diagnostic equation was Logit(P) = −400.53 – 481.88

  20. [ESTABLISHMENT OF A NEW RADIUS DEFECT MODEL BASED ON ULNA ANATOMICAL MEASUREMENT IN RABBITS].

    Liu, Hanjiang; Guo, Ying; Mei, Wei

    2016-02-01

    To introduce a new bone defect model based on the anatomical measurement of radius and ulna in rabbits for offering a standard model for further tissue engineering research. Fifteen healthy 4-month-old New Zealand rabbits were selected for anatomic measurement and radiological measurement of the radius and ulna. Another 30 healthy 4-month-old New Zealand rabbits were randomly divided into groups A, B, and C (n=10). The radius bone defect was created bilaterally in 3 groups. In group A, the periosteum and interosseous membranes were fully removed with jig-saw by approach between extensor carpi radialis muscle and musculus extensor digitorum. The periosteum and interosseous membranes were fully removed in group B, and only periosteum was removed in group C with electric-saw by approach between extensor carpi radialis muscle and flexor digitorum profundus based on anatomical analysis results of ulnar and radial measurement. The gross observation, X-ray, micro-CT three-dimensional reconstruction, bone mineral density (BMD), and bone mineral content (BMC) were observed and recorded at immediate and 15 weeks after operation. HE staining and Masson staining were performed to observe bone formation in the defect areas. Blood vessel injury (1 rabbit), tendon injury (2 rabbits), postoperative hematoma (1 rabbit), and infection (1 rabbit) occurred in group A, postoperative infection (1 rabbit) in group C, and no postoperative complications in group B; the complication rate of group A (50%) was significantly higher than that of groups B (0%) and C (10%) (P0.05). HE staining and Masson staining results showed bone formation in group A, with structure disturbance and sclerosis. New bone formed in groups B and C, cartilage cells were observed in the center of bone cells. The radius bone defect model established by approach between extensor carpi radialis muscle and flexor digitorum profundus is an ideal model because of better exposures, less intra-operative blood loss, less

  1. A model to establish the monetary value of the man-sievert for public exposure

    Schneider, T.; Schieber, C.; Eeckhoudt, L.; Godfroid, P.

    2000-01-01

    The implementation of cost-benefit analysis for the optimisation of radiation protection relies on the adoption of a monetary value of the man-sievert. From the economic point of view, the monetary value of the man-sievert can be seen as a function reflecting the individual and collective preferences associated with the level of exposures and the specificity of the exposure situations. It must thus integrate several dimensions: one dimension, which is independent of the exposure situation, is related to the potential health effects associated with the level of exposure; other dimensions are related to social and equity consideration, reflecting the characteristics of exposure situation: distribution of individual exposures, individual and social risk perception,... In the case of occupational exposure, CEPN has developed a model to define the monetary values of the man-sievert according to the level of individual exposure. This model has been used by some European nuclear utilities for setting their own values to be used in the process of radiological protection optimisation for workers. The question arising now concerns the establishment of this value for public exposure. For this purpose, we have considered one of the main differences between public and worker exposures: i.e. the existence of compensation systems for the radiation induced health effects if they occur for the workers. In the case of public exposure, such systems do not exist, mainly due to the absence of a permanent individual monitoring of exposures and to the low level of individual exposure. A theoretical model was developed to evaluate the willingness to pay to reduce the probability of occurrence of a radiation induced health effects (i.e. to reduce the level of exposure). It shows that, because of the absence of a compensation system for the public, this willingness to pay should be higher when the probability is reduced for the public than for the workers. The result of the numerical

  2. [Establishment and validation of a neonatal pig model of hemolytic jaundice].

    Li, Yong-Fu; Ma, Yue-Lan; Nie, Ling; Chen, Shuan; Jin, Mei-Fang; Wang, San-Lan

    2016-05-01

    To establish a neonatal pig model of hemolytic jaundice. Twelve seven-day-old purebred Yorkshire pigs were randomly divided into an experimental group and a control group (n=6 each). Immunization of New Zealand white rabbits was used to prepare rabbit anti-porcine red blood cell antibodies, and rabbit anti-porcine red blood cell serum was separated. The neonatal pigs in the experimental group were given an intravenous injection of rabbit anti-porcine red blood cell serum (5 mL), and those in the control group were given an intravenous injection of normal saline (5 mL). Venous blood samples were collected every 6 hours for routine blood test and liver function evaluation. The experimental group had a significantly higher serum bilirubin level than the control group at 18 hours after the injection of rabbit anti-porcine red blood cell serum (64±30 μmol/L vs 20±4 μmol/L; Pjaundice simulates the pathological process of human hemolytic jaundice well and provides good biological and material bases for further investigation of neonatal hemolysis.

  3. Iron Biochemistry is Correlated with Amyloid Plaque Morphology in an Established Mouse Model of Alzheimer's Disease.

    Telling, Neil D; Everett, James; Collingwood, Joanna F; Dobson, Jon; van der Laan, Gerrit; Gallagher, Joseph J; Wang, Jian; Hitchcock, Adam P

    2017-10-19

    A signature characteristic of Alzheimer's disease (AD) is aggregation of amyloid-beta (Aβ) fibrils in the brain. Nevertheless, the links between Aβ and AD pathology remain incompletely understood. It has been proposed that neurotoxicity arising from aggregation of the Aβ 1-42 peptide can in part be explained by metal ion binding interactions. Using advanced X-ray microscopy techniques at sub-micron resolution, we investigated relationships between iron biochemistry and AD pathology in intact cortex from an established mouse model over-producing Aβ. We found a direct correlation of amyloid plaque morphology with iron, and evidence for the formation of an iron-amyloid complex. We also show that iron biomineral deposits in the cortical tissue contain the mineral magnetite, and provide evidence that Aβ-induced chemical reduction of iron could occur in vivo. Our observations point to the specific role of iron in amyloid deposition and AD pathology, and may impact development of iron-modifying therapeutics for AD. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

  4. Barriers and facilitators for establishing eating habits, "Póngale Vida®" model

    Ana Raquel Gómez-Alpízar

    2015-12-01

    Full Text Available Introduction: The Preschool Cycle is a period of changes in nutritional status and eating behavior, constituting a fundamental stage for the development of healthy eating habits, where the family plays a major role. Objective: Identify the main barriers and facilitators for healthy eating in preschool age, with the purpose of designing strategies to prevent childhood overweight and obesity. Materials and Methods: The research was conducted under a mixed approach, with a descriptive and transversal type. Sixty parents or caregivers of preschool children who were part of the model during 2014 at the Mariano Cortés School (urban and Canada School (rural, completed the questionnaire and twenty-five participated in the focus groups (one focus group in each school. Results: The barriers that the parents and caregivers faced daily included: food rejection by the child, the influence of peers and even the attitudes of adults who share with the child while eating. The facilitators that encourage healthy eating in this stage of life were: establish clear rules when eating, offer a variety of foods and explain to the child the importance of eating fruits and vegetables in a simple way. Conclusion: The barriers and facilitators to promote healthy eating in this stage of the lifetime, must be include as part of future strategies for the prevention of childhood obesity.

  5. Fishing for Nature's Hits: Establishment of the Zebrafish as a Model for Screening Antidiabetic Natural Products.

    Tabassum, Nadia; Tai, Hongmei; Jung, Da-Woon; Williams, Darren R

    2015-01-01

    Diabetes mellitus affects millions of people worldwide and significantly impacts their quality of life. Moreover, life threatening diseases, such as myocardial infarction, blindness, and renal disorders, increase the morbidity rate associated with diabetes. Various natural products from medicinal plants have shown potential as antidiabetes agents in cell-based screening systems. However, many of these potential "hits" fail in mammalian tests, due to issues such as poor pharmacokinetics and/or toxic side effects. To address this problem, the zebrafish (Danio rerio) model has been developed as a "bridge" to provide an experimentally convenient animal-based screening system to identify drug candidates that are active in vivo. In this review, we discuss the application of zebrafish to drug screening technologies for diabetes research. Specifically, the discovery of natural product-based antidiabetes compounds using zebrafish will be described. For example, it has recently been demonstrated that antidiabetic natural compounds can be identified in zebrafish using activity guided fractionation of crude plant extracts. Moreover, the development of fluorescent-tagged glucose bioprobes has allowed the screening of natural product-based modulators of glucose homeostasis in zebrafish. We hope that the discussion of these advances will illustrate the value and simplicity of establishing zebrafish-based assays for antidiabetic compounds in natural products-based laboratories.

  6. Toward establishing model organisms for marine protists: Successful transfection protocols for Parabodo caudatus (Kinetoplastida: Excavata).

    Gomaa, Fatma; Garcia, Paulo A; Delaney, Jennifer; Girguis, Peter R; Buie, Cullen R; Edgcomb, Virginia P

    2017-09-01

    We developed protocols for, and demonstrated successful transfection of, the free-living kinetoplastid flagellate Parabodo caudatus with three plasmids carrying a fluorescence reporter gene (pEF-GFP with the EF1 alpha promoter, pUB-GFP with Ubiquitin C promoter, and pEYFP-Mitotrap with CMV promoter). We evaluated three electroporation approaches: (1) a square-wave electroporator designed for eukaryotes, (2) a novel microfluidic transfection system employing hydrodynamically-controlled electric field waveforms, and (3) a traditional exponential decay electroporator. We found the microfluidic device provides a simple and efficient platform to quickly test a wide range of electric field parameters to find the optimal set of conditions for electroporation of target species. It also allows for processing large sample volumes (>10 ml) within minutes, increasing throughput 100 times over cuvettes. Fluorescence signal from the reporter gene was detected a few hours after transfection and persisted for 3 days in cells transfected by pEF-GFP and pUB-GFP plasmids and for at least 5 days post-transfection for cells transfected with pEYFP-Mitotrap. Expression of the reporter genes (GFP and YFP) was also confirmed using reverse transcription-PCR (RT-PCR). This work opens the door for further efforts with this taxon and close relatives toward establishing model systems for genome editing. © 2017 Society for Applied Microbiology and John Wiley & Sons Ltd.

  7. [Establishment of sprouting embryoid body model mimicking early embryonic vasculogenesis in human embryo].

    Jiang, Hua; Feng, You-Ji; Xie, Yi; Han, Jin-Lan; Wang, Zack; Chen, Tong

    2008-10-14

    To establish a sprouting embryoid body model mimicking early embryonic vasculogenesis in human embryo. Human embryonic stem were (hESCs) were cultured on the mouse embryo fibroblasts and then were induced to differentiate to form three-dimensional EB. The hEBs were cultured in media containing various angiogenesis-related factors: vascular endothelial growth factor (VEGF), fibroblast growth factor (FGF), endostatin, angiostatin, and platelet factor (PF)-4 of different concentrations for 3 days to observe the sprouting of the hEBs. 3, 3, 3', 3'-tetramethylindo-carbocyanine perchlorate labeled acetylated low density lipoprotein (Dil-AcLDL) was added onto the hEBs foe 4 h Immunofluorescence assay was used to observe if Dil-AcLDL was absorbed and if CD31 was expressed so as to determine the existence of embryonic endothelial cells in the sprouting structures. The ideal culturing condition was analyzed. The differentiated EBs formed sprouting structures in the collagen I matrix containing VEGF and FGF. The sprouts among individual EBs were able to link to each other and form vascular network-like structures. In the presence of VEGF and FGF, the sprouts branching from the EBs assimilated Dil-AcLDL, expressed CD31 and formed a 3-dimensional cylindrical organization. The concentrations of growth factors ideally stimulating sprouting growth were 100 ng/ml of VEGF and 50 ng/ml of FGF. The networks among the EBs were abolished by the angiostatin, endostatin, and PF4. The sprouting from hEBs accumulates embryonic endothelial cells and the sprouting network-like structures are indeed endothelial in nature. Inducing of sprouting EBs is an ideal model that mimics early embryonic vasculogenesis in humans.

  8. Modeling familial clustered breast cancer using published data

    Jonker, MA; Jacobi, CE; Hoogendoorn, WE; Nagelkerke, NJD; de Bock, GH; van Houwelingen, JC

    2003-01-01

    The purpose of this research was to model the familial clustering of breast cancer and to provide an accurate risk estimate for individuals from the general population, based on their family history of breast and ovarian cancer. We constructed a genetic model as an extension of a model by Claus et

  9. Evaluation criterions and establishment of dry eye model of rats induced by BTX-B

    Hai-Feng Zhu

    2015-09-01

    Full Text Available AIM: To establish dry eye model of rats induced by botulinum toxin B(BTX-Band provide the basis for the pathogenesis and experimental treatment of dry eye caused by inflammation. METHODS: Thirty-six healthy female SD rats were selected and divided into four groups randomly, and the experimental group included three groups, which were individually injected 0.1mL 1.25, 5, and 10mU BTX-B solution on the right lacrimal gland; the control group was injected 0.1mL normal saline on the right lacrimal gland, then received Schirmer Ⅰ test(SⅠtand examination of corneal fluorescein(FLstaining respectively at the 3, 7, 14 and 28d. The other 32 rats were selected and divided into two groups randomly, the rats in the experimental group were injected 0.1mL 1.25mU BTX-B solution on the right lacrimal gland and then five rats were randomly chosen to be removed lacrimal gland tissue respectively at the 3, 7, 14, 21, 42d. The Lacritin protein was detected in the qualitative and quantitative way by immunofluorescence and Western-blot, and the histopathological test was received by routine HE staining. RESULTS: The three groups in the experimental group during the preparation of the model appeared that tear secretions decreased and corneal epithelium got damaged at 3d, but there was no significant difference for each other of two changes(P>0.05. The change was reached the peak at 7d and improved at 14d. The tear secretions returned to normal level at 28d, but the damage of corneal epithelium was still existed. The expression of Lacritin protein was only observed in acinar cells of both experimental group and control group, and the content of Lacritin protein in the experimental group decreased significantly. The decreasing situation appeared at 3d, reached the peak at 7d, improved at 14d, began to recover at 28d, and returned to the normal level at 42d. CONCLUSION: Dry eye model of SD rats can be successfully established by lacrimal gland injection of 1.25mU BTX

  10. Modeling timelines for translational science in cancer; the impact of technological maturation.

    Laura M McNamee

    Full Text Available This work examines translational science in cancer based on theories of innovation that posit a relationship between the maturation of technologies and their capacity to generate successful products. We examined the growth of technologies associated with 138 anticancer drugs using an analytical model that identifies the point of initiation of exponential growth and the point at which growth slows as the technology becomes established. Approval of targeted and biological products corresponded with technological maturation, with first approval averaging 14 years after the established point and 44 years after initiation of associated technologies. The lag in cancer drug approvals after the increases in cancer funding and dramatic scientific advances of the 1970s thus reflects predictable timelines of technology maturation. Analytical models of technological maturation may be used for technological forecasting to guide more efficient translation of scientific discoveries into cures.

  11. Entropy, complexity, and Markov diagrams for random walk cancer models.

    Newton, Paul K; Mason, Jeremy; Hurt, Brian; Bethel, Kelly; Bazhenova, Lyudmila; Nieva, Jorge; Kuhn, Peter

    2014-12-19

    The notion of entropy is used to compare the complexity associated with 12 common cancers based on metastatic tumor distribution autopsy data. We characterize power-law distributions, entropy, and Kullback-Liebler divergence associated with each primary cancer as compared with data for all cancer types aggregated. We then correlate entropy values with other measures of complexity associated with Markov chain dynamical systems models of progression. The Markov transition matrix associated with each cancer is associated with a directed graph model where nodes are anatomical locations where a metastatic tumor could develop, and edge weightings are transition probabilities of progression from site to site. The steady-state distribution corresponds to the autopsy data distribution. Entropy correlates well with the overall complexity of the reduced directed graph structure for each cancer and with a measure of systemic interconnectedness of the graph, called graph conductance. The models suggest that grouping cancers according to their entropy values, with skin, breast, kidney, and lung cancers being prototypical high entropy cancers, stomach, uterine, pancreatic and ovarian being mid-level entropy cancers, and colorectal, cervical, bladder, and prostate cancers being prototypical low entropy cancers, provides a potentially useful framework for viewing metastatic cancer in terms of predictability, complexity, and metastatic potential.

  12. Evidence of gene-environment interactions between common breast cancer susceptibility loci and established environmental risk factors

    Nickels, S.; Truong, T.; Hein, R.; Stevens, K.; Buck, K.; Behrens, S.; Eilber, U.; Schmidt, M.; Haberle, L.; Vrieling, A.; Gaudet, M.; Figueroa, J.; Schoof, N.; Spurdle, A.B.; Rudolph, A.; Fasching, P.A.; Hopper, J.L.; Makalic, E.; Schmidt, D.F.; Southey, M.C.; Beckmann, M.W.; Ekici, A.B.; Fletcher, O.; Gibson, L.; Idos, S. Silva; Peto, J.; Humphreys, M.K.; Wang, J; Cordina-Duverger, E.; Menegaux, F.; Nordestgaard, B.G.; Bojesen, S.E.; Lanng, C.; Anton-Culver, H.; Ziogas, A.; Bernstein, L.; Clarke, C.A.; Brenner, H.; Muller, H.; Arndt, V.; Stegmaier, C.; Brauch, H.; Bruning, T.; Harth, V.; Genica, N.; Mannermaa, A.; Kataja, V.; Kosma, V.M.; Hartikainen, J.M.; Lambrechts, D.; Smeets, D.; Neven, P.; Paridaens, R.; Flesch-Janys, D.; Obi, N.; Wang-Gohrke, S.; Couch, F.J.; Olson, J.E.; Vachon, C.M.; Giles, G.G.; Severi, G.; Baglietto, L.; Offit, K.; John, E.M.; Miron, A.; Andrulis, I.L.; Knight, J.A.; Glendon, G.; Mulligan, A.M.; Chanock, S.J.; Lissowska, J.; Liu, J.; Cox, A; Cramp, H.; Connley, D.; Balasubramanian, S.; Dunning, A.M.; Shah, M.; Trentham-Dietz, A.; Newcomb, P.; Titus, L.; Egan, K.; Cahoon, E.K.; Rajaraman, P.; Sigurdson, A.J.; Doody, M.M.; Guenel, P.; Pharoah, P.D.; Schmidt, M.K.; Hall, P.; Easton, D.F.; Garcia-Closas, M.; Milne, R.L.; Chang-Claude, J.; et al.,

    2013-01-01

    Various common genetic susceptibility loci have been identified for breast cancer; however, it is unclear how they combine with lifestyle/environmental risk factors to influence risk. We undertook an international collaborative study to assess gene-environment interaction for risk of breast cancer.

  13. [Establishment of comprehensive prediction model of acute gastrointestinal injury classification of critically ill patients].

    Wang, Yan; Wang, Jianrong; Liu, Weiwei; Zhang, Guangliang

    2018-03-25

    To develop the comprehensive prediction model of acute gastrointestinal injury (AGI) grades of critically ill patients. From April 2015 to November 2015, the binary channel gastrointestinal sounds (GIS) monitor system which has been developed and verified by the research group was used to gather and analyze the GIS of 60 consecutive critically ill patients who were admitted in Critical Care Medicine of Chinese PLA General Hospital. Also, the AGI grades (Grande I(-IIII(, the higher the level, the heavier the gastrointestinal dysfunction) were evaluated. Meanwhile, the clinical data and physiological and biochemical indexes of included patients were collected and recorded daily, including illness severity score (APACHE II( score, consisting of the acute physiology score, age grade and chronic health evaluation), sequential organ failure assessment (SOFA score, including respiration, coagulation, liver, cardioascular, central nervous system and kidney) and Glasgow coma scale (GCS); body mass index, blood lactate and glucose, and treatment details (including mechanical ventilation, sedatives, vasoactive drugs, enteral nutrition, etc.) Then principal component analysis was performed on the significantly correlated GIS (five indexes of gastrointestinal sounds were found to be negatively correlated with AGI grades, which included the number, percentage of time, mean power, maximum power and maximum time of GIS wave from the channel located at the stomach) and clinical factors after standardization. The top 5 post-normalized main components were selected for back-propagation (BP) neural network training, to establish comprehensive AGI grades models of critically ill patients based on the neural network model. The 60 patients aged 19 to 98 (mean 54.6) years and included 42 males (70.0%). There were 22 cases of multiple fractures, 15 cases of severe infection, 7 cases of cervical vertebral fracture, 7 cases of aortic repair, 5 cases of post-toxicosis and 4 cases of cerebral

  14. Establishment of artery smooth muscle cell proliferation model after subarachnoid hemorrhage in rats

    Yu-jie CHEN

    2011-12-01

    Full Text Available Objective The current paper aims to simulate the effects of hemolytic products on intracranial vascular smooth muscle cell after subarachnoid hemorrhage(SAH,and probe into the molecular mechanism and strategy for the prevention and cure of vascular proliferation after SAH.Methods Thirty Sprague-Dawley rats were randomly divided into three groups,including sham-operated,24 h after SAH,and 72 h after SAH groups.The artificial hemorrhage model around the common carotid artery was established for the latter two groups.The animals were put to death after 24 h and 72 h to take the common carotid artery,and to measure the expression level of PCNA,SM-α-actin protein,and mRNA in the smooth muscle cell.Results The PCNA mRNA expression was significantly up-regulated in the 24-h group(P < 0.01.The expression in the 72-h group was lower than that of the 24-h group(P < 0.01,whereas it was still remarkably higher than that of the sham group(P < 0.01.The SM-α-actin mRNA expression in the smooth muscle cell in the 24-h and 72-h groups decreased compared with that of the Sham group(P < 0.05,whereas the 72-h group was significantly lower than that of the 24-h group(P < 0.05.The protein expression of PCNA and SM-α-actin showed a similar trend.Conclusion The current experiment simulates better effects of the hemolytic products on vascular smooth muscle cell after SAH.It also shows that artificial hemorrhage around the common carotid artery could stimulate vascular smooth muscle cell to change from contractile phenotype into synthetic phenotype,and improve it to proliferate.

  15. Embryonic Zebrafish Model - A Well-Established Method for Rapidly Assessing the Toxicity of Homeopathic Drugs

    Gupta, Himanshu R; Patil, Yogesh; Singh, Dipty

    2016-01-01

    in this study. The embryonic zebrafish model is recommended as a well-established method for rapidly assessing the toxicity of homeopathic drugs. PMID:28127503

  16. Computational Modeling of Micrometastatic Breast Cancer Radiation Dose Response

    Smith, Daniel L.; Debeb, Bisrat G. [Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Morgan Welch Inflammatory Breast Cancer Research Program and Clinic, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Thames, Howard D. [Department of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Woodward, Wendy A., E-mail: wwoodward@mdanderson.org [Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Morgan Welch Inflammatory Breast Cancer Research Program and Clinic, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States)

    2016-09-01

    Purpose: Prophylactic cranial irradiation (PCI) involves giving radiation to the entire brain with the goals of reducing the incidence of brain metastasis and improving overall survival. Experimentally, we have demonstrated that PCI prevents brain metastases in a breast cancer mouse model. We developed a computational model to expand on and aid in the interpretation of our experimental results. Methods and Materials: MATLAB was used to develop a computational model of brain metastasis and PCI in mice. Model input parameters were optimized such that the model output would match the experimental number of metastases per mouse from the unirradiated group. An independent in vivo–limiting dilution experiment was performed to validate the model. The effect of whole brain irradiation at different measurement points after tumor cells were injected was evaluated in terms of the incidence, number of metastases, and tumor burden and was then compared with the corresponding experimental data. Results: In the optimized model, the correlation between the number of metastases per mouse and the experimental fits was >95. Our attempt to validate the model with a limiting dilution assay produced 99.9% correlation with respect to the incidence of metastases. The model accurately predicted the effect of whole-brain irradiation given 3 weeks after cell injection but substantially underestimated its effect when delivered 5 days after cell injection. The model further demonstrated that delaying whole-brain irradiation until the development of gross disease introduces a dose threshold that must be reached before a reduction in incidence can be realized. Conclusions: Our computational model of mouse brain metastasis and PCI correlated strongly with our experiments with unirradiated mice. The results further suggest that early treatment of subclinical disease is more effective than irradiating established disease.

  17. [Establishment of oxygen and glucose deprive model of in vitro cultured hippocampal neuron and effect of ligustrazine on intracellular Ca+ level in model neurons].

    Wan, Hai-tong; Wang, Yu; Yang, Jie-hong

    2007-03-01

    To establish the oxygen and glucose deprive (OGD) model in cultured hippocampal neuron and study the effect of ligustrazine on intracellular Ca2+ level in the model neurons. The OGD model was established in cultured hippocampal neuron, and the intracellular Ca2+ level in it was detected by laser scanning confocal microscope (LSCM). The OGD model was successfully established in cultured hippocampal neurons; the intracellular Ca2+ level in the OGD model group was significantly higher than that in the blank control group (P neuron, which could be antagonized by ligustrazine, indicating that ligustrazine has a protective effect on hippocampal neuron from hypoxic-ischemic injury.

  18. A comparative review of radiation-induced cancer risk models

    Lee, Seung Hee; Kim, Ju Youl [FNC Technology Co., Ltd., Yongin (Korea, Republic of); Han, Seok Jung [Risk and Environmental Safety Research Division, Korea Atomic Energy Research Institute, Daejeon (Korea, Republic of)

    2017-06-15

    With the need for a domestic level 3 probabilistic safety assessment (PSA), it is essential to develop a Korea-specific code. Health effect assessments study radiation-induced impacts; in particular, long-term health effects are evaluated in terms of cancer risk. The objective of this study was to analyze the latest cancer risk models developed by foreign organizations and to compare the methodology of how they were developed. This paper also provides suggestions regarding the development of Korean cancer risk models. A review of cancer risk models was carried out targeting the latest models: the NUREG model (1993), the BEIR VII model (2006), the UNSCEAR model (2006), the ICRP 103 model (2007), and the U.S. EPA model (2011). The methodology of how each model was developed is explained, and the cancer sites, dose and dose rate effectiveness factor (DDREF) and mathematical models are also described in the sections presenting differences among the models. The NUREG model was developed by assuming that the risk was proportional to the risk coefficient and dose, while the BEIR VII, UNSCEAR, ICRP, and U.S. EPA models were derived from epidemiological data, principally from Japanese atomic bomb survivors. The risk coefficient does not consider individual characteristics, as the values were calculated in terms of population-averaged cancer risk per unit dose. However, the models derived by epidemiological data are a function of sex, exposure age, and attained age of the exposed individual. Moreover, the methodologies can be used to apply the latest epidemiological data. Therefore, methodologies using epidemiological data should be considered first for developing a Korean cancer risk model, and the cancer sites and DDREF should also be determined based on Korea-specific studies. This review can be used as a basis for developing a Korean cancer risk model in the future.

  19. Phenotypic heterogeneity in modeling cancer evolution.

    Ali Mahdipour-Shirayeh

    Full Text Available The unwelcome evolution of malignancy during cancer progression emerges through a selection process in a complex heterogeneous population structure. In the present work, we investigate evolutionary dynamics in a phenotypically heterogeneous population of stem cells (SCs and their associated progenitors. The fate of a malignant mutation is determined not only by overall stem cell and non-stem cell growth rates but also differentiation and dedifferentiation rates. We investigate the effect of such a complex population structure on the evolution of malignant mutations. We derive exactly calculated results for the fixation probability of a mutant arising in each of the subpopulations. The exactly calculated results are in almost perfect agreement with the numerical simulations. Moreover, a condition for evolutionary advantage of a mutant cell versus the wild type population is given in the present study. We also show that microenvironment-induced plasticity in invading mutants leads to more aggressive mutants with higher fixation probability. Our model predicts that decreasing polarity between stem and non-stem cells' turnover would raise the survivability of non-plastic mutants; while it would suppress the development of malignancy for plastic mutants. The derived results are novel and general with potential applications in nature; we discuss our model in the context of colorectal/intestinal cancer (at the epithelium. However, the model clearly needs to be validated through appropriate experimental data. This novel mathematical framework can be applied more generally to a variety of problems concerning selection in heterogeneous populations, in other contexts such as population genetics, and ecology.

  20. Inference of Low and High-Grade Glioma Gene Regulatory Networks Delineates the Role of Rnd3 in Establishing Multiple Hallmarks of Cancer.

    Kim Clarke

    2015-07-01

    Full Text Available Gliomas are a highly heterogeneous group of brain tumours that are refractory to treatment, highly invasive and pro-angiogenic. Glioblastoma patients have an average survival time of less than 15 months. Understanding the molecular basis of different grades of glioma, from well differentiated, low-grade tumours to high-grade tumours, is a key step in defining new therapeutic targets. Here we use a data-driven approach to learn the structure of gene regulatory networks from observational data and use the resulting models to formulate hypothesis on the molecular determinants of glioma stage. Remarkably, integration of available knowledge with functional genomics datasets representing clinical and pre-clinical studies reveals important properties within the regulatory circuits controlling low and high-grade glioma. Our analyses first show that low and high-grade gliomas are characterised by a switch in activity of two subsets of Rho GTPases. The first one is involved in maintaining normal glial cell function, while the second is linked to the establishment of multiple hallmarks of cancer. Next, the development and application of a novel data integration methodology reveals novel functions of RND3 in controlling glioma cell migration, invasion, proliferation, angiogenesis and clinical outcome.

  1. Modelling Nanoparticle Diffusion into Cancer Tumors

    Podduturi, Vishwa Priya; Derosa, Pedro

    2011-03-01

    Cancer is one of the major, potentially deadly diseases and has been for years. Non-specific delivery of the drug can damage healthy tissue seriously affecting in many cases the patient's living condition. Nanoparticles are being used for a targeted drug delivery thereby reducing the dose. In addition, metallic nanoparticles are being used in thermal treatment of cancer cells where nanoparticles help concentrate heat in the tumor and away from living tissue. We proposed a model that combines random walk with diffusion principles. The particle drift velocity is taken from the Hagen-Poiseuille equation and the velocity profile of the particle at the pores in the capillary wall is obtained using the Coventorware software. Pressure gradient and concentration gradient through the capillary wall are considered. Simulations are performed in Matlab using the Monte Carlo technique. Number of particles leaving the blood vessel through a pore is obtained as a function of blood pressure, the osmotic pressure, temperature, particle concentration, blood vessel radius, and pore size, and the relative effect of each of the parameters is discussed.

  2. Comparative molecular analysis of early and late cancer cachexia-induced muscle wasting in mouse models.

    Sun, Rulin; Zhang, Santao; Lu, Xing; Hu, Wenjun; Lou, Ning; Zhao, Yan; Zhou, Jia; Zhang, Xiaoping; Yang, Hongmei

    2016-12-01

    Cancer-induced muscle wasting, which commonly occurs in cancer cachexia, is characterized by impaired quality of life and poor patient survival. To identify an appropriate treatment, research on the mechanism underlying muscle wasting is essential. Thus far, studies on muscle wasting using cancer cachectic models have generally focused on early cancer cachexia (ECC), before severe body weight loss occurs. In the present study, we established models of ECC and late cancer cachexia (LCC) and compared different stages of cancer cachexia using two cancer cachectic mouse models induced by colon-26 (C26) adenocarcinoma or Lewis lung carcinoma (LLC). In each model, tumor-bearing (TB) and control (CN) mice were injected with cancer cells and PBS, respectively. The TB and CN mice, which were euthanized on the 24th day or the 36th day after injection, were defined as the ECC and ECC-CN mice or the LCC and LCC-CN mice. In addition, the tissues were harvested and analyzed. We found that both the ECC and LCC mice developed cancer cachexia. The amounts of muscle loss differed between the ECC and LCC mice. Moreover, the expression of some molecules was altered in the muscles from the LCC mice but not in those from the ECC mice compared with their CN mice. In conclusion, the molecules with altered expression in the muscles from the ECC and LCC mice were not exactly the same. These findings may provide some clues for therapy which could prevent the muscle wasting in cancer cachexia from progression to the late stage.

  3. Three-dimensional in vitro cancer models: a short review

    Wang, Chengyang; Sun, Wei; Tang, Zhenyu; Li, Lingsong; Zhao, Yu; Yao, Rui

    2014-01-01

    The re-creation of the tumor microenvironment including tumor–stromal interactions, cell–cell adhesion and cellular signaling is essential in cancer-related studies. Traditional two-dimensional (2D) cell culture and animal models have been proven to be valid in some areas of explaining cancerous cell behavior and interpreting hypotheses of possible mechanisms. However, a well-defined three-dimensional (3D) in vitro cancer model, which mimics tumor structures found in vivo and allows cell–cell and cell–matrix interactions, has gained strong interest for a wide variety of diagnostic and therapeutic applications. This communication attempts to provide a representative overview of applying 3D in vitro biological model systems for cancer related studies. The review compares and comments on the differences in using 2D models, animal models and 3D in vitro models for cancer research. Recent technologies to construct and develop 3D in vitro cancer models are summarized in aspects of modeling design, fabrication technique and potential application to biology, pathogenesis study and drug testing. With the help of advanced engineering techniques, the development of a novel complex 3D in vitro cancer model system will provide a better opportunity to understand crucial cancer mechanisms and to develop new clinical therapies. (topical review)

  4. [Identification of Circulating Tumor Cell(CTC)in Breast Cancer Patients Using a Newly Established CTC Detecting System].

    Nagata, Takuya; Ohnaga, Takashi; Lu, Xiao Long; Watanabe, Toru; Hirano, Katsuhisa; Okumura, Tomoyuki; Tsukada, Kazuhiro

    2015-10-01

    We developed a new circulating tumor cell (CTC) chip in order to identify CTCs in the peripheral blood of cancer patients. In this study, we aimed to identify CTCs in the blood of breast cancer patients by using this CTC detecting system. In addition, we used this system to evaluate the response to anticancer agents. We were able to identify CTCs in 5 of 6 patients. In addition, the system showed that the number of CTCs had decreased after chemotherapy. Thus, the CTC detecting system was useful in the identification of CTCs in the breast cancer patients and in the early prediction of response to anticancer agents.

  5. Dialogues on cancer survivorship: a new model of international cooperation.

    Stein, Kevin; Mattioli, Vittorio

    2013-06-01

    The authors describe the rationale and background of the present supplement to Cancer intended to stimulate a dialogue among researchers from Europe and North America regarding important issues faced by cancer survivors. Through jointly written articles addressing various aspects of cancer survivorship, each manuscript reports on the similarities, disparities, and problems viewed from the point of view of each author's respective continent. The supplement is meant to create a springboard for increased collaboration and aid in the development of a shared care model to improve the quality of cancer care, both during and after the completion of primary treatment. We hope that this effort may represent a new model of international cooperation, which is fruitful not only for the field of scientific research but also for identifying and sharing new approaches to the care and management of cancer survivorship issues, ultimately bringing improvements to quality of life of the growing population of cancer survivors. Copyright © 2013 American Cancer Society.

  6. [Establishment and comparison of stoma and stoma-free heterotopic small intestine transplantation models in mice].

    Meng, Ning; Pan, Zhijian; Liu, Yadong; Xu, Xin; Shen, Jiliang; Shen, Bo

    2016-03-01

    To establish stoma and stoma-free murine models of heterotopic small intestine transplantation in order to choose a more effective and reliable model. A total of 140 male 8-10 weeks age C57BL/6(B6) mice weighted 25-30 g were enrolled in the experiment. Syngeneic heterotopic small intestine transplantation was performed between C57BL/6 mice, and recipient mice were divided into either stoma or stoma-free group. Heterotopic small intestine transplantation was performed in 70 mice, with 35 mice in each group. After closing the proximal end of the graft by ligation, the distal end of graft was exteriorized as a stoma then secured to the skin of the abdominal wall in stoma group. In stoma-free group, the distal end of graft was anastomosed end-to-side to the recipient ileum. Successful rate of operation, two-week survival rate, operation time, associated complications, postoperative care time and body weight change were recorded and compared between two groups. The successful rate of stoma group was 65.7%, while it was 80.0% of stoma-free group (χ(2)=1.806, P=0.179). The operation time of donor in stoma group was (48.1±6.6) minutes, while it was (47.2±5.9) minutes in stoma-free group (t=0.598, P=0.552). The operation time of recipient in stoma group was (77.9±9.1) minutes, while it was (76.4±8.3) minutes in stoma-free group (t=0.683, P=0.497). The cold ischemic time of graft in stoma group was (34.7±4.0) minutes, while it was (33.9±4.6) minutes in stoma-free group(t=0.667, P=0.507). The two-week survival rate of stoma group was 45.7%, and it was 77.1% of stoma-free group(χ(2)=7.295, P=0.007). The stoma group had more complications[54.3%(19/35) vs. 22.9%(8/35), χ(2)=7.295, P=0.007], which needed more postoperative care time(191 min vs. 35 min). The weight loss in stoma group in the third day after operation was more significant [(81.52±5.20)% vs. (85.46±4.65)%, t=2.856, P=0.006]. By 2 weeks after operation, the weight of mice in both groups retruned to 95% of

  7. [Establishment of β-aminopropionitrile-induced aortic dissection model in C57Bl/6J mice].

    Gao, Y X; Liu, Y T; Zhang, Y Y; Qiu, J J; Zhao, T T; Yu, C A; Zheng, J G

    2018-02-24

    Objective: To establish the mouse aorta dissection (AD) model through drinking water containing β-aminopropionitrile (BAPN). Methods: Forty 3-week-old C57B1/6J male mice were divided into four groups according to randomized block design: control, 0.2, 0.4 and 0.8 g·kg(-1)·d(-1) BAPN groups (dissolving respective dose of BAPN in the drinking water, n= 10 each group). Arterial systolic blood pressure and heart rate were measured weekly in conscious, restrained mice using a noninvasive computerized tail-cuff system. Mice those died of rupture of aortic dissecting aneurysm during the study were autopsied and the aorta was examined. After 4 weeks, survived mice were sacrificed by an overdose of sodium pentobarbital and the whole aorta was harvested and analyzed. Results: The incidence of AD and the mortality of ruptured AD was 0 and 0 in control group, 30% (3/10) and 20% (2/10) in 0.2 g·kg(-1)·d(-1) BAPN group, 50% (5/10) and 40% (4/10) in 0.4 g·kg(-1)·d(-1) BAPN group, 90% (9/10) and 70% (7/10) in 0.8 g·kg(-1)·d(-1) BAPN group (both Pmice died of dissecting aneurysm rupture during the experiment, among which 5 dissecting aneurysms were mainly located in the thoracic aorta and 2 dissecting aneurysms in abdominal aorta. The diameters of thoracic aorta and abdominal aorta were (1.38±0.19) and (1.23±0.13) mm in control group, (2.43±1.56) and (1.30±0.26) mm in 0.2 g·kg(-1)·d(-1) BAPN group, (2.45±1.28) and (1.30±0.31) mm in 0.4 g·kg(-1)·d(-1) BAPN group, (2.87±0.57) and (1.95±0.81) mm in 0.8 g·kg(-1)·d(-1) BAPN group (both Pmice also increased in proportion with BAPN concentration increase. Furthermore, blood-filled false lumen formation and elastic fibers fragmentation were evidenced in hematoxylin-eosin stained and Vitoria blue-Sirius red stained aortic cross-sections of mice in the 0.8 g·kg(-1)·d(-1) BAPN group. Conclusion: BAPN treatment induced aortic dissection model in C57Bl/6J mice can serve as a useful wild-type mouse model for the

  8. Short-term spheroid culture of primary colorectal cancer cells as an in vitro model for personalizing cancer medicine

    Jeppesen, Maria; Hagel, Grith; Glenthoj, Anders

    2017-01-01

    Chemotherapy treatment of cancer remains a challenge due to the molecular and functional heterogeneity displayed by tumours originating from the same cell type. The pronounced heterogeneity makes it difficult for oncologists to devise an effective therapeutic strategy for the patient. One approac...... and combinations most commonly used for treatment of colorectal cancer. In summary, short-term spheroid culture of primary colorectal adenocarcinoma cells represents a promising in vitro model for use in personalized medicine....... for increasing treatment efficacy is to test the chemosensitivity of cancer cells obtained from the patient's tumour. 3D culture represents a promising method for modelling patient tumours in vitro. The aim of this study was therefore to evaluate how closely short-term spheroid cultures of primary colorectal...... cancer cells resemble the original tumour. Colorectal cancer cells were isolated from human tumour tissue and cultured as spheroids. Spheroid cultures were established with a high success rate and remained viable for at least 10 days. The spheroids exhibited significant growth over a period of 7 days...

  9. Fenretinide-induced caspase-8 activation and apoptosis in an established model of metastatic neuroblastoma

    Raguénez, Gilda; Mühlethaler-Mottet, Annick; Meier, Roland; Duros, Caroline; Bénard, Jean; Gross, Nicole

    2009-01-01

    Resistance of high-risk metastatic neuroblastoma (HR-NB) to high dose chemotherapy (HD-CT) raises a major therapeutic challenge in pediatric oncology. Patients are treated by maintenance CT. For some patients, an adjuvant retinoid therapy is proposed, such as the synthetic retinoid fenretinide (4-HPR), an apoptotic inducer. Recent studies demonstrated that NB metastasis process is enhanced by the loss of caspase-8 involved in the Integrin-Mediated Death (IMD) process. As the role of caspase-8 appears to be critical in preventing metastasis, we aimed at studying the effect of 4-HPR on caspase-8 expression in metastatic neuroblasts. We used the human IGR-N-91 MYCN-amplified NB experimental model, able to disseminate in vivo from the primary nude mouse tumor xenograft (PTX) into myocardium (Myoc) and bone marrow (BM) of the animal. NB cell lines, i.e., IGR-N-91 and SH-EP, were treated with various doses of Fenretinide (4-HPR), then cytotoxicity was analyzed by MTS proliferation assay, apoptosis by the propidium staining method, gene or protein expressions by RT-PCR and immunoblotting and caspases activity by colorimetric protease assays. The IGR-N-91 parental cells do not express detectable caspase-8. However the PTX cells established from the primary tumor in the mouse, are caspase-8 positive. In contrast, metastatic BM and Myoc cells show a clear down-regulation of the caspase-8 expression. In parallel, the caspases -3, -9, -10, Bcl-2, or Bax expressions were unchanged. Our data show that in BM, compared to PTX cells, 4-HPR up-regulates caspase-8 expression that parallels a higher sensitivity to apoptotic cell death. Stable caspase-8-silenced SH-EP cells appear more resistant to 4-HPR-induced cell death compared to control SH-EP cells. Moreover, 4-HPR synergizes with drugs since apoptosis is restored in VP16- or TRAIL-resistant-BM cells. These results demonstrate that 4-HPR in up-regulating caspase-8 expression, restores and induces apoptotic cell death in

  10. Mouse models of estrogen receptor-positive breast cancer

    Shakur Mohibi

    2011-01-01

    Full Text Available Breast cancer is the most frequent malignancy and second leading cause of cancer-related deaths among women. Despite advances in genetic and biochemical analyses, the incidence of breast cancer and its associated mortality remain very high. About 60 - 70% of breast cancers are Estrogen Receptor alpha (ER-α positive and are dependent on estrogen for growth. Selective estrogen receptor modulators (SERMs have therefore provided an effective targeted therapy to treat ER-α positive breast cancer patients. Unfortunately, development of resistance to endocrine therapy is frequent and leads to cancer recurrence. Our understanding of molecular mechanisms involved in the development of ER-α positive tumors and their resistance to ER antagonists is currently limited due to lack of experimental models of ER-α positive breast cancer. In most mouse models of breast cancer, the tumors that form are typically ER-negative and independent of estrogen for their growth. However, in recent years more attention has been given to develop mouse models that develop different subtypes of breast cancers, including ER-positive tumors. In this review, we discuss the currently available mouse models that develop ER-α positive mammary tumors and their potential use to elucidate the molecular mechanisms of ER-α positive breast cancer development and endocrine resistance.

  11. Modelling in 3D the olive trees cultures in order to establish the forces (interval) needed for automatic harvesting

    Babanatsas, T.; Glăvan, D. O.; Babanatis Merce, R. M.; Maris, S. A.

    2018-01-01

    The purpose of this study is to bring as much as possible, close to real situation the 3D modelling for the olive trees in order to establish the necessary forces for automatic harvesting (harvesting robots). To fulfil our goal we have at our disposal different ways to do modelling very close to the real situation. One way is to use reality capture software (its results being photos) that are converted into a real 3D model, the disadvantage of the method being a mesh model that is not accurate enough. The reasonable alternative is to develop an experiment by measuring a sample orchard of olive trees (experiment who took place in Halkidiki, Greece, measuring over 120 trees). After establishing the real dimensions, we adopted as model the media that we have measured (the height of the tree, the thickness of branches, number of branches, etc.), model which we consider closer to the reality and therefor more suitable for our simulation.

  12. Computer modeling of lung cancer diagnosis-to-treatment process.

    Ju, Feng; Lee, Hyo Kyung; Osarogiagbon, Raymond U; Yu, Xinhua; Faris, Nick; Li, Jingshan

    2015-08-01

    We introduce an example of a rigorous, quantitative method for quality improvement in lung cancer care-delivery. Computer process modeling methods are introduced for lung cancer diagnosis, staging and treatment selection process. Two types of process modeling techniques, discrete event simulation (DES) and analytical models, are briefly reviewed. Recent developments in DES are outlined and the necessary data and procedures to develop a DES model for lung cancer diagnosis, leading up to surgical treatment process are summarized. The analytical models include both Markov chain model and closed formulas. The Markov chain models with its application in healthcare are introduced and the approach to derive a lung cancer diagnosis process model is presented. Similarly, the procedure to derive closed formulas evaluating the diagnosis process performance is outlined. Finally, the pros and cons of these methods are discussed.

  13. [Risk factor analysis of the patients with solitary pulmonary nodules and establishment of a prediction model for the probability of malignancy].

    Wang, X; Xu, Y H; Du, Z Y; Qian, Y J; Xu, Z H; Chen, R; Shi, M H

    2018-02-23

    Objective: This study aims to analyze the relationship among the clinical features, radiologic characteristics and pathological diagnosis in patients with solitary pulmonary nodules, and establish a prediction model for the probability of malignancy. Methods: Clinical data of 372 patients with solitary pulmonary nodules who underwent surgical resection with definite postoperative pathological diagnosis were retrospectively analyzed. In these cases, we collected clinical and radiologic features including gender, age, smoking history, history of tumor, family history of cancer, the location of lesion, ground-glass opacity, maximum diameter, calcification, vessel convergence sign, vacuole sign, pleural indentation, speculation and lobulation. The cases were divided to modeling group (268 cases) and validation group (104 cases). A new prediction model was established by logistic regression analying the data from modeling group. Then the data of validation group was planned to validate the efficiency of the new model, and was compared with three classical models(Mayo model, VA model and LiYun model). With the calculated probability values for each model from validation group, SPSS 22.0 was used to draw the receiver operating characteristic curve, to assess the predictive value of this new model. Results: 112 benign SPNs and 156 malignant SPNs were included in modeling group. Multivariable logistic regression analysis showed that gender, age, history of tumor, ground -glass opacity, maximum diameter, and speculation were independent predictors of malignancy in patients with SPN( P prediction model for the probability of malignancy as follow: p =e(x)/(1+ e(x)), x=-4.8029-0.743×gender+ 0.057×age+ 1.306×history of tumor+ 1.305×ground-glass opacity+ 0.051×maximum diameter+ 1.043×speculation. When the data of validation group was added to the four-mathematical prediction model, The area under the curve of our mathematical prediction model was 0.742, which is greater

  14. [Establishment of rat model with diabetes mellitus and concomitant periodontitis and the carotid artery lesions in the model rats].

    Ren, X Y; Wang, C; Liu, X; Li, H; Gao, J H; Ge, X J

    2017-12-09

    Objectives: To establish SD rat model with type 2 diabetes mellitus (DM) and concomitant chronic periodontitis (CP) and to evaluate the influence of periodontitis on the vascular lesions of type 2 diabetes rats. Methods: Totally 241 clean level SD rats were randomly divided into four groups, group A (normal control, NC, n= 27), group B (DM, n= 34), group C (CP, n= 90) and group D (DM+CP, n= 90). The rats of DM group were fed with high-fat and high-sugar diet for 8 to 10 weeks, and then were multiply injected with small dose streptozotocin under the condition of ice bath. Blood sugar levels after the injection were dynamically monitored at 72 h, 1 week, 2 weeks and 4 weeks, respectively. The CP model was established by means of ligation. Bilateral maxillary first and second molars were selected and ligated using 0.2 mm orthodontic wires binding with 4-0 surgical suture soaked with Porphyromonas gingivalis (Pg) suspension. After a period of 14 weeks, all the rats were put to death. Maxillary samples were subjected to methylene blue staining to observe alveolar bone loss. Bilateral carotid artery specimens were collected. The left carotid artery specimens were used to detect the prevalence of Pg using quantitative real-time PCR. The right carotid artery specimens were used to observe pathological changes. Results: Blood sugar levels of rats in group B and D increased and changed sharply after Streptozotocin injection with in 1 week. Symptoms of 'more drink, more food and body weight loss' appeared. The fasting blood glucose (FBG) was more than 7.8 mmol/L and (or) the random blood glucose (RBG) was more than 17.8 mmol/L. Both FBG and RBG became stable after 2 to 3 weeks. Levels of HbA1C in group B and D ([7.32±0.45]%, [9.41±0.45]%) were significantly higher than that of group A ([4.02±0.45]%) ( Pdiabetes vascular lesions.

  15. Creating a Sustainable Model for Establishing Youth Gardens in Schools and Childcare Centers

    Wright, William; Friese, Bettina; Carrel, Aaron; Meinen, Amy

    2013-01-01

    Purpose/Objectives: The goal of the program was to establish youth gardens across Wisconsin by conducting workshops for school staff and childcare providers on how to start and sustain a youth garden with limited resources. Methods: Evaluation utilized an end-of-workshop questionnaire and follow-up survey. The end-of-workshop questionnaire focused…

  16. Ultrasonographic screening for breast cancer using the recall criteria established by the Japan Association of Breast and Thyroid Sonology (JABTS)

    Tsukamoto, Noriko; Tsunoda-Shimizu, Hiroko; Kikuchi, Mari

    2007-01-01

    As is the case in many other countries, mammography is currently used in Japan for breast cancer screening. However, as it cannot detect lesions in dense breasts such as those of young women, ultrasound (US) imaging is used for this purpose. Although there have been numerous reports of US screening, the results obtained using the recall criteria stipulated by the Japan Association of Breast and Thyroid Sonology (JABTS) has not yet been reported. We have performed US screening based on the JABTS guidelines for three years. Technologists perform the examinations, and physicians select recall cases on the basis of these criteria. So far there have been 17,089 attendees, of whom 90% were less than 50 years old. The recall rate was 3.6% (616/17,089). The results of further examinations were confirmed in 452 of these 616 recalled women, and breast cancer was detected in 48 (0.28%) of them. Cancer was detected early in 37 (80.5%) of these 48 cases. Mammography was unable to detect cancer in 16 (43%) of the cases. Although the high recall rate of US screening has been mentioned previously, we wish to emphasize that US breast cancer screening is effective, particularly in younger women. Furthermore, the reasonable recall rate ensures that a high quality of detection is maintained. (author)

  17. How to establish knowledge sharing from the very first moment in critical and risky Business Model Innovation project

    Lindgren, Peter; Aagaard, Annabeth; Ulldall, Lene

    Joint action and knowledge sharing are fundamental aspects of business model innovation for businesses to meet the complex Business Model Innovation challenges; for example, think about 12 business jointly innovating on the establishment of a new concept of a balanced energy plant project where...... practice tools have had little to say on this topic because for many years perception, action, and cognition have been studied without taking their role in social interaction related to BMI seriously (Sebanz 2006). However the establishment of a “room” for social BMI interaction is essential at the very...

  18. Queensland Youth Cancer Service: A Partnership Model to Facilitate Access to Quality Care for Young People Diagnosed with Cancer.

    Bradford, Natalie K; Henney, Roslyn; Walker, Rick; Walpole, Euan; Kennedy, Glen; Nicholls, Wayne; Pinkerton, Ross

    2018-06-01

    Global recognition of the need to improve outcomes for adolescents and young adults (AYA) with cancer has led to the development of specific oncology programs and services. In Australia, Youth Cancer Services (YCS) are now established across the country. While each service has been shaped by nationally agreed principles, program development has been influenced by local policy and geographic differences. Queensland is a vast state with a widely dispersed population; coordination of cancer services for young people across this landscape presents unique challenges. The Queensland YCS (QYCS) work in a consultative partnership model with primary treating teams, across both pediatric and adult tertiary cancer services. Understanding how cancer services approach challenges and service development can provide guidance for other developing services. In this article, we describe the goals and development of QYCS and review the outcomes achieved in the service to date. We reviewed referral data and retrieved statewide clinical activity from the web-based data system. We compared these data with cancer registry data to identify disparities and areas for service development. While the service has achieved notable outcomes, challenges remain. These include recruitment of appropriately skilled and trained health professionals for this newly developing area of oncology. In addition, there is an ongoing need to advocate for this relatively small patient group, and to promote awareness and understanding of the need for AYA-specific services. With the dispersed population and concentration of services in metropolitan Brisbane, identifying and testing new innovative models, including telehealth, to reach all AYA diagnosed with cancer regardless of location of care are priorities.

  19. Therapeutic effect of angiogenesis inhibitor combined with radiotherapy on liver metastasis model of colon cancer

    Jin Liugen; Zhou Shifu

    2005-01-01

    Objective: To observe the therapeutic effect of angiogenesis inhibitor combined with radiotherapy on liver metastasis model of colon cancer. Methods: Nude mice liver metastasis model of colon cancer was established with human colon cancer cells line (LS174T) inoculated into mice' spleen and followed by splenectomy. Angiogenesis inhibitor 2-ME and radiotherapy were administered after-wads. The growth inhibition effect on metastases and neovessel was examined. Results: The incidences of liver metastasis were 100% in this intrasplenic injection model. The mean weight and microvessel density 4 weeks after inoculation were 53.6 ± 4.7 mg, 8.4 ± 1.7 in treatment group as compared to 173.9 ± 11.6 mg, 41.2 ± 6.3 in control group respectively. Conclusion: 2-ME combined with radiotherapy has significant inhibition on the growth of liver metastases. Angiogenesis inhibition is one of the mechanisms of its efficiency. (authors)

  20. Neuromuscular Alterations After Ankle Sprains: An Animal Model to Establish Causal Links After Injury.

    Lepley, Lindsey K; McKeon, Patrick O; Fitzpatrick, Shane G; Beckemeyer, Catherine L; Uhl, Timothy L; Butterfield, Timothy A

    2016-10-01

    The mechanisms that contribute to the development of chronic ankle instability are not understood. Investigators have developed a hypothetical model in which neuromuscular alterations that stem from damaged ankle ligaments are thought to affect periarticular and proximal muscle activity. However, the retrospective nature of these studies does not allow a causal link to be established. To assess temporal alterations in the activity of 2 periarticular muscles of the rat ankle and 2 proximal muscles of the rat hind limb after an ankle sprain. Controlled laboratory study. Laboratory. Five healthy adult male Long Evans rats (age = 16 weeks, mass = 400.0 ± 13.5 g). Indwelling fine-wire electromyography (EMG) electrodes were implanted surgically into the biceps femoris, medial gastrocnemius, vastus lateralis, and tibialis anterior muscles of the rats. We recorded baseline EMG measurements while the rats walked on a motor-driven treadmill and then induced a closed lateral ankle sprain by overextending the lateral ankle ligaments. After ankle sprain, the rats were placed on the treadmill every 24 hours for 7 days, and we recorded postsprain EMG data. Onset time of muscle activity, phase duration, sample entropy, and minimal detectable change (MDC) were assessed and compared with baseline using 2-tailed dependent t tests. Compared with baseline, delayed onset time of muscle activity was exhibited in the biceps femoris (baseline = -16.7 ± 54.0 milliseconds [ms]) on day 0 (5.2 ± 64.1 ms; t 4 = -4.655, P = .043) and tibialis anterior (baseline = 307.0 ± 64.2 ms) muscles on day 3 (362.5 ± 55.9 ms; t 4 = -5.427, P = .03) and day 6 (357.3 ± 39.6 ms; t 4 = -3.802, P = .02). Longer phase durations were observed for the vastus lateralis (baseline = 321.9 ± 92.6 ms) on day 3 (401.3 ± 101.2 ms; t 3 = -4.001, P = .03), day 4 (404.1 ± 93.0 ms; t 3 = -3.320, P = .048), and day 5 (364.6 ± 105.2 ms; t 3 = -3.963, P = .03) and for the tibialis anterior (baseline = 103.9 ± 16.4 ms

  1. Multistep Model of Cervical Cancer: Participation of miRNAs and Coding Genes

    Angelica Judith Granados López

    2014-09-01

    Full Text Available Aberrant miRNA expression is well recognized as an important step in the development of cancer. Close to 70 microRNAs (miRNAs have been implicated in cervical cancer up to now, nevertheless it is unknown if aberrant miRNA expression causes the onset of cervical cancer. One of the best ways to address this issue is through a multistep model of carcinogenesis. In the progression of cervical cancer there are three well-established steps to reach cancer that we used in the model proposed here. The first step of the model comprises the gene changes that occur in normal cells to be transformed into immortal cells (CIN 1, the second comprises immortal cell changes to tumorigenic cells (CIN 2, the third step includes cell changes to increase tumorigenic capacity (CIN 3, and the final step covers tumorigenic changes to carcinogenic cells. Altered miRNAs and their target genes are located in each one of the four steps of the multistep model of carcinogenesis. miRNA expression has shown discrepancies in different works; therefore, in this model we include miRNAs recording similar results in at least two studies. The present model is a useful insight into studying potential prognostic, diagnostic, and therapeutic miRNAs.

  2. Diagnostic accuracy of non-contrast abdominal CT scans performed as follow-up for patients with an established cancer diagnosis: a retrospective study.

    Semaan, Hassan; Bazerbashi, Mohamad F; Siesel, Geoffrey; Aldinger, Paul; Obri, Tawfik

    2018-03-01

    To determine the accuracy and non-detection rate of cancer related findings (CRFs) on follow-up non-contrast-enhanced CT (NECT) versus contrast-enhanced CT (CECT) images of the abdomen in patients with a known cancer diagnosis. A retrospective review of 352 consecutive CTs of the abdomen performed with and without IV contrast between March 2010 and October 2014 for follow-up of cancer was included. Two radiologists independently assessed the NECT portions of the studies. The reader was provided the primary cancer diagnosis and access to the most recent prior NECT study. The accuracy and non-detection rates were determined by comparing our results to the archived reports as a gold standard. A total of 383 CRFs were found in the archived reports of the 352 abdominal CTs. The average non-detection rate for the NECTs compared to the CECTs was 3.0% (11.5/383) with an accuracy of 97.0% (371.5/383) in identifying CRFs. The most common findings missed were vascular thrombosis with a non-detection rate of 100%. The accuracy for non-vascular CRFs was 99.1%. Follow-up NECT abdomen studies are highly accurate in the detection of CRFs in patients with an established cancer diagnosis, except in cases where vascular involvement is suspected.

  3. Establishment of land model at the Shika Nuclear Power Plant. Mainly, on rock board classification

    Katagawa, Hideki; Hashimoto, Toru; Hirano, Shuji

    1999-01-01

    In order to grasp engineering properties of basic land of constructions, there is rock board classification as a method to classify whole of rock board to some groups considerable to be nearly equal on its properties. Among the method, various methods in response to its aim and characteristics are devised, and for a classification to hard rock board, the Denken type rock board classification considering degree of weathering to its main element and so forth are well known. The basic rock board of the Shika Nuclear Power Plant is composed of middle and hard types of rock, and its weathering is limited to its shallow portion, most of which are held at fresh condition. For such land, a new classification standard in response to characteristics of land was established. Here were introduced on a progress to establish a new classification standard, its application results and rock board properties. (G.K.)

  4. Multidrug Resistance in Breast Cancer: From In Vitro Models to Clinical Studies

    Wind, N.S.; Holen, I.

    2011-01-01

    The development of multidrug resistance (MDR) and subsequent relapse on therapy is a widespread problem in breast cancer, but our understanding of the underlying molecular mechanisms is incomplete. Numerous studies have aimed to establish the role of drug transporter pumps in MDR and to link their expression to response to chemotherapy. The ATP-binding cassette (ABC) transporters are central to breast cancer MDR, and increases in ABC expression levels have been shown to correlate with decreases in response to various chemotherapy drugs and a reduction in overall survival. But as there is a large degree of redundancy between different ABC transporters, this correlation has not been seen in all studies. This paper provides an introduction to the key molecules associated with breast cancer MDR and summarises evidence of their potential roles reported from model systems and clinical studies. We provide possible explanations for why despite several decades of research, the precise role of ABC transporters in breast cancer MDR remains elusive

  5. Holistic models for end of life care: establishing the place of culture

    Selman, L.; Speck, P.; Barfield, R.C.; Gysels, M.; Higginson, I.J.; Harding, R.

    2014-01-01

    Introduction This article presents a holistic model for clinical palliative care and research which expands and improves previous models by fully recognizing the place of culture in illness. Methods Literature review and philosophical enquiry. Results Holistic models of patient care are essential to

  6. Water use in four model tropical plant associations established in the lowlands of Costa Rica

    Marco V Gutiérrez-Soto

    2008-12-01

    Full Text Available We examined soil water use patterns of four model plant associations established in the North Caribbean lowlands of Costa Rica by comparing the stable hydrogen isotope composition, δD, in xylem sap and in soil water at different depths, under rainy and dry conditions. Four 5-year-old model plant associations composed of 2 tree species (Hyeronima alchorneoides and Cedrela odorata having different architecture and phenology were studied. Average tree height was 8.9 and 7.6 m, respectively. Each tree species was grown in monoculture and in polyculture with 2 perennial monocotyledons (Euterpe oleracea and Heliconia imbricata. Maximum rooting depth at the time of δD determination was ~ 2 m for almost all species. Most roots of all species were concentrated in the upper soil layers. Stomatal conductance to water vapor (gS was higher in the deciduous C. odorata than in the evergreen H. alchorneoides; within each species, gS did not differ when the trees were grown in mono or in polyculture. During the rainy season, gradients in soil water δD were not observed. Average rainy season xylem sap δD did not differ among members of the plant combinations tested (-30 ‰, and was more similar to δD values of shallow soil water. Under dry conditions, volumetric soil water content declined from 50 to ~ 35%, and modest gradients in soil water δD were observed. xylem sap δD obtained during dry conditions was significantly lower than rainy season values. xylem sap δD of plants growing in the four associations varied between -9 and -22‰, indicating that shallow water was predominantly absorbed during the dry period too. Differences in xylem sap δD of trees and monocots were also detected, but no significant patterns emerged. The results suggest that: a the plant associations examined extracted water predominantly from shallow soil layers (Examinamos los patrones de uso de agua del suelo de cuatro asociaciones vegetales establecidas en el Caribe norte de

  7. Using the Logistic Regression model in supporting decisions of establishing marketing strategies

    Cristinel CONSTANTIN

    2015-12-01

    Full Text Available This paper is about an instrumental research regarding the using of Logistic Regression model for data analysis in marketing research. The decision makers inside different organisation need relevant information to support their decisions regarding the marketing strategies. The data provided by marketing research could be computed in various ways but the multivariate data analysis models can enhance the utility of the information. Among these models we can find the Logistic Regression model, which is used for dichotomous variables. Our research is based on explanation the utility of this model and interpretation of the resulted information in order to help practitioners and researchers to use it in their future investigations

  8. Synthetic matrix metalloproteinase inhibitors inhibit growth of established breast cancer osteolytic lesions and prolong survival in mice

    Winding, Bent; NicAmhlaoibh, Róisín; Misander, Henriette

    2002-01-01

    Breast cancer frequently leads to incurable bone metastasis. Essential requirements for the development of bone metastasis are cell-cell and cell-matrix interactions, release of bioactive growth factors and cytokines, and removal of large amounts of bone matrix. Matrix metalloproteinases (MMPs...

  9. Essential role of radiation therapy for the treatment of pancreatic cancer. Novel study concepts and established treatment recommendations

    Dobiasch, Sophie; Goerig, Nicole L.; Fietkau, Rainer; Combs, Stephanie E.

    2018-01-01

    Pancreatic cancer is one of the most aggressive human tumors and the incidence has increased over the last 6 years. In the majority of cases the disease is already in an advanced stage at the time of diagnosis where surgery, the only curative treatment, is no longer an option and explains the still abysmal overall survival. The role of radiation therapy as treatment option for patients with pancreatic cancer is controversially discussed although radiation oncology has emerged as a central pillar in the combined oncological treatment. The present manuscript gives an overview of advanced radiotherapeutic strategies in the context of chemotherapy and surgery according to the current American Society of Clinical Oncology (ASCO) guidelines in comparison with the German guidelines and to elucidate the role of radiation therapy for the treatment of pancreatic cancer. Advanced modern radiotherapeutic techniques in combination with individualized high-precision radiation concepts are new therapeutic approaches for pancreatic cancer in a multimodal setting with tolerable side effects. Several clinical studies together with experimental approaches are in process, to deliver further evidence and ultimately allow true personalized medicine. (orig.) [de

  10. Evidence of gene-environment interactions between common breast cancer susceptibility loci and established environmental risk factors

    Nickels, Stefan; Truong, Thérèse; Hein, Rebecca

    2013-01-01

    Various common genetic susceptibility loci have been identified for breast cancer; however, it is unclear how they combine with lifestyle/environmental risk factors to influence risk. We undertook an international collaborative study to assess gene-environment interaction for risk of breast cance...

  11. Mathematical modeling for novel cancer drug discovery and development.

    Zhang, Ping; Brusic, Vladimir

    2014-10-01

    Mathematical modeling enables: the in silico classification of cancers, the prediction of disease outcomes, optimization of therapy, identification of promising drug targets and prediction of resistance to anticancer drugs. In silico pre-screened drug targets can be validated by a small number of carefully selected experiments. This review discusses the basics of mathematical modeling in cancer drug discovery and development. The topics include in silico discovery of novel molecular drug targets, optimization of immunotherapies, personalized medicine and guiding preclinical and clinical trials. Breast cancer has been used to demonstrate the applications of mathematical modeling in cancer diagnostics, the identification of high-risk population, cancer screening strategies, prediction of tumor growth and guiding cancer treatment. Mathematical models are the key components of the toolkit used in the fight against cancer. The combinatorial complexity of new drugs discovery is enormous, making systematic drug discovery, by experimentation, alone difficult if not impossible. The biggest challenges include seamless integration of growing data, information and knowledge, and making them available for a multiplicity of analyses. Mathematical models are essential for bringing cancer drug discovery into the era of Omics, Big Data and personalized medicine.

  12. Prediction Model for Gastric Cancer Incidence in Korean Population.

    Bang Wool Eom

    Full Text Available Predicting high risk groups for gastric cancer and motivating these groups to receive regular checkups is required for the early detection of gastric cancer. The aim of this study is was to develop a prediction model for gastric cancer incidence based on a large population-based cohort in Korea.Based on the National Health Insurance Corporation data, we analyzed 10 major risk factors for gastric cancer. The Cox proportional hazards model was used to develop gender specific prediction models for gastric cancer development, and the performance of the developed model in terms of discrimination and calibration was also validated using an independent cohort. Discrimination ability was evaluated using Harrell's C-statistics, and the calibration was evaluated using a calibration plot and slope.During a median of 11.4 years of follow-up, 19,465 (1.4% and 5,579 (0.7% newly developed gastric cancer cases were observed among 1,372,424 men and 804,077 women, respectively. The prediction models included age, BMI, family history, meal regularity, salt preference, alcohol consumption, smoking and physical activity for men, and age, BMI, family history, salt preference, alcohol consumption, and smoking for women. This prediction model showed good accuracy and predictability in both the developing and validation cohorts (C-statistics: 0.764 for men, 0.706 for women.In this study, a prediction model for gastric cancer incidence was developed that displayed a good performance.

  13. Mathematical pointing model establishment of the visual tracking theodolite for satellites in two kinds of observation methods.

    Zhang, Yuncheng

    The mathematical pointing model is establishment of the visual tracking theodolite for satellites in two kinds of observation methods at Yunnan Observatory, which is related to the digitalisation reform and the optical-electronic technique reform, is introduced respectively in this paper.

  14. Obesity-Linked Mouse Models of Liver Cancer | Center for Cancer Research

    Jimmy Stauffer, Ph.D., and colleagues working with Robert  Wiltrout, Ph.D., in CCR’s Cancer and Inflammation Program, along with collaborators in the Laboratory of Human Carcinogenesis, have developed a novel mouse model that demonstrates how fat-producing phenotypes can influence the development of hepatic cancer.   The team recently reported their findings in Cancer Research.

  15. Organoids as Models for Neoplastic Transformation | Office of Cancer Genomics

    Cancer models strive to recapitulate the incredible diversity inherent in human tumors. A key challenge in accurate tumor modeling lies in capturing the panoply of homo- and heterotypic cellular interactions within the context of a three-dimensional tissue microenvironment. To address this challenge, researchers have developed organotypic cancer models (organoids) that combine the 3D architecture of in vivo tissues with the experimental facility of 2D cell lines.

  16. POLARIZATION IMAGING AND SCATTERING MODEL OF CANCEROUS LIVER TISSUES

    DONGZHI LI

    2013-07-01

    Full Text Available We apply different polarization imaging techniques for cancerous liver tissues, and compare the relative contrasts for difference polarization imaging (DPI, degree of polarization imaging (DOPI and rotating linear polarization imaging (RLPI. Experimental results show that a number of polarization imaging parameters are capable of differentiating cancerous cells in isotropic liver tissues. To analyze the contrast mechanism of the cancer-sensitive polarization imaging parameters, we propose a scattering model containing two types of spherical scatterers and carry on Monte Carlo simulations based on this bi-component model. Both the experimental and Monte Carlo simulated results show that the RLPI technique can provide a good imaging contrast of cancerous tissues. The bi-component scattering model provides a useful tool to analyze the contrast mechanism of polarization imaging of cancerous tissues.

  17. Establishment of A Malignant Pleural Effusion Mouse Model with Lewis Lung 
Carcinoma Cell Lines Expressing Enhanced Green Fluorescent Protein

    Xingqun MA

    2012-06-01

    Full Text Available Background and objective Malignant pleural effusion (MPE is a poor prognosis factor in patients with advanced lung cancer. The aim of this study is to establish a mouse model of MPE using Lewis lung carcinoma (LLC cell lines expressing enhanced green fluorescent protein (EGFP. Methods The mouse model was created by injecting LLC-EGFP cells directly into the pleural cavity of mice that were sacrificed periodically. The dynamic growth and metastasis of tumor cells were screened using in vivo fluorescence imaging. The remaining mice were subjected to transverse computed tomography (CT imaging periodically to analyze the formation rate of pleural effusion. The survival rate and tumor metastasis were also observed. Pleural fluid was gently aspirated using a 1 mL syringe and its volume was measured. When two or more mice bore pleural effusion at the same time, we calculated the average volume. The correlation of pleural effusion with the integrated optical density (IOD were analyzed. Results Four days after the inoculation of LLC-EGFP cells, green fluorescence was observed by opening the chest wall. The tumor formation rate was 100%, and the IOD gradually increased after inoculation. The metastasis sites were mediastinal, and the hilar lymph nodes were contralateral pleural as well as pericardial. The metastasis rates were 87%, 73% and 20%, respectively. The CT scan revealed that the formation rates of pleural effusion on days 7, 14 and 21 were 13%, 46% and 53%, respectively. The average volume of pleural effusion increased obviously on day 10 and peaked on day 16 with a value of 0.5 mL. The mean survival time of nude mice was 28.8 days. The volume of pleural effusion and IOD were significantly correlated (r=0.91, P<0.000,1. Conclusion A mouse model of lung cancer malignant pleural effusion was successfully established by injecting LLC lines expressing EGFP into the pleural cavity under a microscope. The model can enable dynamic observations of the

  18. Assessing ballast treatment standards for effect on rate of establishment using a stochastic model of the green crab

    Cynthia Cooper

    2012-03-01

    Full Text Available This paper describes a stochastic model used to characterize the probability/risk of NIS establishment from ships' ballast water discharges. Establishment is defined as the existence of a sufficient number of individuals of a species to provide for a sustained population of the organism. The inherent variability in population dynamics of organisms in their native or established environments is generally difficult to quantify. Muchqualitative information is known about organism life cycles and biotic and abiotic environmental pressures on the population, but generally little quantitative data exist to develop a mechanistic model of populations in such complex environments. Moreover, there is little quantitative data to characterize the stochastic fluctuations of population size over time even without accounting for systematic responses to biotic and abiotic pressures. This research applies an approach using life-stage density and fecundity measures reported in research to determine a stochastic model of an organism's population dynamics. The model is illustrated withdata from research studies on the green crab that span a range of habitats of the established organism and were collected over some years to represent a range of time-varying biotic and abiotic conditions that are expected to exist in many receiving environments. This model is applied to introductions of NIS at the IMO D-2 and the U.S. ballast water discharge standard levels designated as Phase Two in the United States Coast Guard'sNotice of Proposed Rulemaking. Under a representative range of ballast volumes discharged at U.S. ports, the average rate of establishment of green crabs for ballast waters treated to the IMO-D2 concentration standard (less than 10 organisms/m3 is predicted to be reduced to about a third the average rate from untreated ballast water discharge. The longevity of populations from the untreated ballast water discharges is expected to be reducedby about 90% by

  19. Prognostic significance of smoking in addition to established risk factors in patients with Dukes B and C colorectal cancer: a retrospective analysis.

    Diamantis, N; Xynos, I D; Amptulah, S; Karadima, M; Skopelitis, H; Tsavaris, N

    2013-01-01

    To investigate the prognostic significance of smoking in addition to established risk factors in patients with Dukes stage B and C colorectal cancer (CRC). 291 consecutive non-selected CRC patients were studied retrospectively. Twenty-three variables were examined using a regression statistical model to identify relevant prognostic factors related to disease free survival (DFS) and overall survival (OS). On multivariate analysis DFS was found to be negatively affected in patients with a smoking history of ≤10 pack-years vs. non-smokers (p<0.016). Additionally, performance status (PS)<90 (p<0.001), Dukes stage C (p<0.001) and elevated tumor markers (p<0.001) at the time of diagnosis were found to adversely affect DFS. Smoking also had a significant association with relapse. Patients with a smoking history of ≤10 pack-years had 2.45 (p<0.018) higher risk of recurrence compared to patients with no smoking history. OS was influenced by Karnofsky performance status (PS), Dukes stage, and elevated tumor markers. In particular patients with PS< 90 had a 4.69-fold higher risk of death (p<0.001) than patients with better PS. Stage C disease was associated with 2.27-fold higher risk of death (p<0.001) than stage B disease, and patients with elevated tumor markers at the time of diagnosis had 2.74-fold higher risk of death (p<0.014) when compared to those whose tumor markers were normal at presentation. Our study associates smoking and relapse incidence in non-clinical- trial CRC patients and reiterates the prognostic significance of PS, stage and tumor markers at the time of diagnosis.

  20. Establishing 3d numerical reservoir analogues : Modelling the formation of sand bodies in deltaic environments

    van der Vegt, H.; Storms, J.E.A.; Walstra, D.J.R.

    2014-01-01

    The assessment and production of hydrocarbon resources incorporates geological models created from core and wireline well data, as well as seismic data. This data is spatially discrete but is used create a spatially continuous model. However, the heterogeneity within depositional environments is on

  1. Improved numerical solutions for chaotic-cancer-model

    Muhammad Yasir

    2017-01-01

    Full Text Available In biological sciences, dynamical system of cancer model is well known due to its sensitivity and chaoticity. Present work provides detailed computational study of cancer model by counterbalancing its sensitive dependency on initial conditions and parameter values. Cancer chaotic model is discretized into a system of nonlinear equations that are solved using the well-known Successive-Over-Relaxation (SOR method with a proven convergence. This technique enables to solve large systems and provides more accurate approximation which is illustrated through tables, time history maps and phase portraits with detailed analysis.

  2. Improved numerical solutions for chaotic-cancer-model

    Yasir, Muhammad; Ahmad, Salman; Ahmed, Faizan; Aqeel, Muhammad; Akbar, Muhammad Zubair

    2017-01-01

    In biological sciences, dynamical system of cancer model is well known due to its sensitivity and chaoticity. Present work provides detailed computational study of cancer model by counterbalancing its sensitive dependency on initial conditions and parameter values. Cancer chaotic model is discretized into a system of nonlinear equations that are solved using the well-known Successive-Over-Relaxation (SOR) method with a proven convergence. This technique enables to solve large systems and provides more accurate approximation which is illustrated through tables, time history maps and phase portraits with detailed analysis.

  3. Establishment and calibration of consensus process model for nitrous oxide dynamics in water quality engineering

    Domingo-Felez, Carlos

    that enhance cost and energy efficiency in BNR, while maintaining effluent quali-ty. Now, increasing attention is placed on direct emissions of nitrous oxide (N2O) as by-product of BNR; N2O is a greenhouse gas (GHG) with a high warming potential and also an ozone depleting chemical compound. Several N2O...... process modelling efforts aim to reproduce ex-perimental data with mathematical equations, structuring our understanding of the system. Various mechanistic models with different structures describ-ing N2O production have been proposed, but no consensus exists between researchers. Hence, the existing plant......-wide GHG models still lack a complete biological process model that can be integrated in a methodology that assess-es N2O emissions and their impact on overall plant performance. A mathematical model structure that describes N2O production during biological nitrogen removal is proposed. Two autotrophic...

  4. [Establishment of a 3D finite element model of human skull using MSCT images and mimics software].

    Huang, Ping; Li, Zheng-dong; Shao, Yu; Zou, Dong-hua; Liu, Ning-guo; Li, Li; Chen, Yuan-yuan; Wan, Lei; Chen, Yi-jiu

    2011-02-01

    To establish a human 3D finite element skull model, and to explore its value in biomechanics analysis. The cadaveric head was scanned and then 3D skull model was created using Mimics software based on 2D CT axial images. The 3D skull model was optimized by preprocessor along with creation of the surface and volume meshes. The stress changes, after the head was struck by an object or the head hit the ground directly, were analyzed using ANSYS software. The original 3D skull model showed a large number of triangles with a poor quality and high similarity with the real head, while the optimized model showed high quality surface and volume meshes with a small number of triangles comparatively. The model could show the local and global stress changes effectively. The human 3D skull model can be established using MSCT and Mimics software and provides a good finite element model for biomechanics analysis. This model may also provide a base for the study of head stress changes following different forces.

  5. Cancer evolution and immunity in a rat colorectal carcinogenesis model

    Vannucci, Luca; Fišerová, Anna; Horváth, Ondřej; Rossmann, Pavel; Mosca, F.; Pospíšil, Miloslav

    2004-01-01

    Roč. 25, - (2004), s. 973-981 ISSN 1019-6439 R&D Projects: GA ČR GV312/98/K034; GA AV ČR IAA7020006 Institutional research plan: CEZ:AV0Z5020903 Keywords : cancer * cancer model * colorectal adenocarcinoma Subject RIV: EE - Microbiology, Virology Impact factor: 3.056, year: 2004

  6. Risk Prediction Models for Other Cancers or Multiple Sites

    Developing statistical models that estimate the probability of developing other multiple cancers over a defined period of time will help clinicians identify individuals at higher risk of specific cancers, allowing for earlier or more frequent screening and counseling of behavioral changes to decrease risk.

  7. Decision support model for establishing the optimal energy retrofit strategy for existing multi-family housing complexes

    Hong, Taehoon; Koo, Choongwan; Kim, Hyunjoong; Seon Park, Hyo

    2014-01-01

    The number of multi-family housing complexes (MFHCs) over 15 yr old in South Korea is expected to exceed 5 million by 2015. Accordingly, the demand for energy retrofit in the deteriorating MFHCs is rapidly increasing. This study aimed to develop a decision support model for establishing the optimal energy retrofit strategy for existing MFHCs. It can provide clear criteria for establishing the carbon emissions reduction target (CERT) and allow efficient budget allocation for conducting the energy retrofit. The CERT for “S” MFHC, one of MFHCs located in Seoul, as a case study, was set at 23.0% (electricity) and 27.9% (gas energy). In the economic and environmental assessment, it was determined that scenario #12 was the optimal scenario (ranked second with regard to NPV 40 (net present value at year 40) and third with regard to SIR 40 (saving to investment ratio at year 40). The proposed model could be useful for owners, construction managers, or policymakers in charge of establishing energy retrofit strategy for existing MFHCs. It could allow contractors in a competitive bidding process to rationally establish the CERT and select the optimal energy retrofit strategy. It can be also applied to any other country or sector in a global environment. - Highlights: • The proposed model was developed to establish the optimal energy retrofit strategy. • Advanced case-based reasoning was applied to establish the community-based CERT. • Energy simulation was conducted to analyze the effects of energy retrofit strategy. • The optimal strategy can be finally selected based on the LCC and LCCO 2 analysis. • It could be extended to any other country or sector in the global environment

  8. Towards Measures to Establish the Relevance of Climate Model Output for Decision Support

    Clarke, L.; Smith, L. A.

    2007-12-01

    How exactly can decision-support and policy making benefit from the use of multiple climate model experiments in terms of coping with the uncertainties on climate change projections? Climate modelling faces challenges beyond those of weather forecasting or even seasonal forecasting, as with climate we are now (and will probably always be) required to extrapolate to regimes in which we have no relevant forecast-verification archive. This suggests a very different approach from traditional methods of mixing models and skill based weighting to gain profitable probabilistic information when a large forecast-verification archive is in hand. In the case of climate, it may prove more rational to search for agreement between our models (in distribution), the aim being to determine the space and timescales on which, given our current understanding, the details of the simulation models are unimportant. This suggestion and others from Smith (2002, Proc. National Acad. Sci. USA 4 (99): 2487-2492) are interpreted in the light of recent advances. Climate models are large nonlinear dynamical systems which insightfully but imperfectly reflect the evolving weather patterns of the Earth. Their use in policy making and decision support assumes both that they contain sufficient information regarding reality to inform the decision, and that this information can be effectively communicated to the decision makers. There is nothing unique about climate modeling and these constraints, they apply in all cases where scientific modeling is applied to real-word actions (other than, perhaps, the action of improving our models). Starting with the issue of communication, figures from the 2007 IPCC Summary for Policy Makers will be constructively criticized from the perspective of decision makers, specifically those of the energy sector and the insurance/reinsurance sector. More information on basic questions of reliability and robustness would be of significant value when determining how heavily

  9. A communication model of shared decision making: accounting for cancer treatment decisions.

    Siminoff, Laura A; Step, Mary M

    2005-07-01

    The authors present a communication model of shared decision making (CMSDM) that explicitly identifies the communication process as the vehicle for decision making in cancer treatment. In this view, decision making is necessarily a sociocommunicative process whereby people enter into a relationship, exchange information, establish preferences, and choose a course of action. The model derives from contemporary notions of behavioral decision making and ethical conceptions of the doctor-patient relationship. This article briefly reviews the theoretical approaches to decision making, notes deficiencies, and embeds a more socially based process into the dynamics of the physician-patient relationship, focusing on cancer treatment decisions. In the CMSDM, decisions depend on (a) antecedent factors that have potential to influence communication, (b) jointly constructed communication climate, and (c) treatment preferences established by the physician and the patient.

  10. Essential role of radiation therapy for the treatment of pancreatic cancer. Novel study concepts and established treatment recommendations

    Dobiasch, Sophie [Technical University of Munich (TUM), Department of Radiation Oncology, Klinikum rechts der Isar, Munich (Germany); Goerig, Nicole L.; Fietkau, Rainer [Friedrich-Alexander-Universitaet Erlangen-Nuernberg, Department of Radiation Oncology, Universitaetsklinikum Erlangen, Erlangen (Germany); Combs, Stephanie E. [Technical University of Munich (TUM), Department of Radiation Oncology, Klinikum rechts der Isar, Munich (Germany); Helmholtz Zentrum Muenchen, Institute of Innovative Radiotherapy (iRT), Department of Radiation Sciences (DRS), Neuherberg (Germany)

    2018-03-15

    Pancreatic cancer is one of the most aggressive human tumors and the incidence has increased over the last 6 years. In the majority of cases the disease is already in an advanced stage at the time of diagnosis where surgery, the only curative treatment, is no longer an option and explains the still abysmal overall survival. The role of radiation therapy as treatment option for patients with pancreatic cancer is controversially discussed although radiation oncology has emerged as a central pillar in the combined oncological treatment. The present manuscript gives an overview of advanced radiotherapeutic strategies in the context of chemotherapy and surgery according to the current American Society of Clinical Oncology (ASCO) guidelines in comparison with the German guidelines and to elucidate the role of radiation therapy for the treatment of pancreatic cancer. Advanced modern radiotherapeutic techniques in combination with individualized high-precision radiation concepts are new therapeutic approaches for pancreatic cancer in a multimodal setting with tolerable side effects. Several clinical studies together with experimental approaches are in process, to deliver further evidence and ultimately allow true personalized medicine. (orig.) [German] Das Pankreaskarzinom gehoert zu den aggressivsten menschlichen Tumoren und verzeichnete in den letzten 6 Jahren eine steigende Inzidenz. Die Diagnose wird meist erst im fortgeschrittenen Stadium gestellt; dies schliesst haeufig eine primaer kurative Intervention mithilfe der chirurgischen Resektion aus und bedingt die hohe Mortalitaet. Obwohl die Strahlentherapie im multimodalen Therapieansatz des Pankreaskarzinoms eine zentrale Saeule darstellt, wird die Rolle der Strahlentherapie in der Literatur kontrovers diskutiert. Der vorliegende Beitrag bietet eine Uebersicht moderner Bestrahlungsstrategien im interdisziplinaeren Konzept gemaess der Leitlinien der American Society of Clinical Oncology (ASCO) im Vergleich zu den

  11. α Centauri A as a potential stellar model calibrator: establishing the nature of its core

    Nsamba, B.; Monteiro, M. J. P. F. G.; Campante, T. L.; Cunha, M. S.; Sousa, S. G.

    2018-05-01

    Understanding the physical process responsible for the transport of energy in the core of α Centauri A is of the utmost importance if this star is to be used in the calibration of stellar model physics. Adoption of different parallax measurements available in the literature results in differences in the interferometric radius constraints used in stellar modelling. Further, this is at the origin of the different dynamical mass measurements reported for this star. With the goal of reproducing the revised dynamical mass derived by Pourbaix & Boffin, we modelled the star using two stellar grids varying in the adopted nuclear reaction rates. Asteroseismic and spectroscopic observables were complemented with different interferometric radius constraints during the optimisation procedure. Our findings show that best-fit models reproducing the revised dynamical mass favour the existence of a convective core (≳ 70% of best-fit models), a result that is robust against changes to the model physics. If this mass is accurate, then α Centauri A may be used to calibrate stellar model parameters in the presence of a convective core.

  12. Warburg effect and translocation-induced genomic instability: two yeast models for cancer cells

    Tosato, Valentina; Grüning, Nana-Maria; Breitenbach, Michael; Arnak, Remigiusz; Ralser, Markus; Bruschi, Carlo V.

    2013-01-01

    Yeast has been established as an efficient model system to study biological principles underpinning human health. In this review we focus on yeast models covering two aspects of cancer formation and progression (i) the activity of pyruvate kinase (PK), which recapitulates metabolic features of cancer cells, including the Warburg effect, and (ii) chromosome bridge-induced translocation (BIT) mimiking genome instability in cancer. Saccharomyces cerevisiae is an excellent model to study cancer cell metabolism, as exponentially growing yeast cells exhibit many metabolic similarities with rapidly proliferating cancer cells. The metabolic reconfiguration includes an increase in glucose uptake and fermentation, at the expense of respiration and oxidative phosphorylation (the Warburg effect), and involves a broad reconfiguration of nucleotide and amino acid metabolism. Both in yeast and humans, the regulation of this process seems to have a central player, PK, which is up-regulated in cancer, and to occur mostly on a post-transcriptional and post-translational basis. Furthermore, BIT allows to generate selectable translocation-derived recombinants (“translocants”), between any two desired chromosomal locations, in wild-type yeast strains transformed with a linear DNA cassette carrying a selectable marker flanked by two DNA sequences homologous to different chromosomes. Using the BIT system, targeted non-reciprocal translocations in mitosis are easily inducible. An extensive collection of different yeast translocants exhibiting genome instability and aberrant phenotypes similar to cancer cells has been produced and subjected to analysis. In this review, we hence provide an overview upon two yeast cancer models, and extrapolate general principles for mimicking human disease mechanisms in yeast.

  13. WARBURG EFFECT AND TRANSLOCATION-INDUCED GENOMIC INSTABILITY: TWO YEAST MODELS FOR CANCER CELLS

    Valentina eTosato

    2013-01-01

    Full Text Available Yeast has been established as an efficient model system to study biological principles underpinning human health. In this review we focus on yeast models covering two aspects of cancer formation and progression i the activity of pyruvate kinase (PK, which recapitulates metabolic features of cancer cells, including the Warburg effect, and ii Bridge-Induced chromosome Translocation (BIT mimicking genome instability in cancer. Saccharomyces cerevisiae is an excellent model to study cancer cell metabolism, as exponentially growing yeast cells exhibit many metabolic similarities with rapidly proliferating cancer cells. The metabolic reconfiguration includes an increase in glucose uptake and fermentation, at the expense of respiration and oxidative phosphorylation (the Warburg effect, and involves a broad reconfiguration of nucleotide and amino acid metabolism. Both in yeast and humans, the regulation of this process seems to have a central player, pyruvate kinase, which is up-regulated in cancer, and to occur mostly on a post-transcriptional and posttranslational basis. Furthermore, BIT allows to generate selectable translocation-derived recombinants (translocants, between any two desired chromosomal locations, in wild-type yeast strains transformed with a linear DNA cassette carrying a selectable marker flanked by two DNA sequences homologous to different chromosomes. Using the Bridge-Induced Translocation system, targeted non-reciprocal translocations in mitosis are easily inducible. An extensive collection of different yeast translocants exhibiting genome instability and aberrant phenotypes similar to cancer cells has been produced and subjected to analysis. In this review, we hence provide an overview upon two yeast cancer models, and extrapolate general principles for mimicking human disease mechanisms in yeast.

  14. Warburg effect and translocation-induced genomic instability: two yeast models for cancer cells

    Tosato, Valentina [International Centre for Genetic Engineering and Biotechnology, Trieste (Italy); Grüning, Nana-Maria [Cambridge System Biology Center, Department of Biochemistry, University of Cambridge, Cambridge (United Kingdom); Breitenbach, Michael [Division of Genetics, Department of Cell Biology, University of Salzburg, Salzburg (Austria); Arnak, Remigiusz [International Centre for Genetic Engineering and Biotechnology, Trieste (Italy); Ralser, Markus [Cambridge System Biology Center, Department of Biochemistry, University of Cambridge, Cambridge (United Kingdom); Bruschi, Carlo V., E-mail: bruschi@icgeb.org [International Centre for Genetic Engineering and Biotechnology, Trieste (Italy)

    2013-01-18

    Yeast has been established as an efficient model system to study biological principles underpinning human health. In this review we focus on yeast models covering two aspects of cancer formation and progression (i) the activity of pyruvate kinase (PK), which recapitulates metabolic features of cancer cells, including the Warburg effect, and (ii) chromosome bridge-induced translocation (BIT) mimiking genome instability in cancer. Saccharomyces cerevisiae is an excellent model to study cancer cell metabolism, as exponentially growing yeast cells exhibit many metabolic similarities with rapidly proliferating cancer cells. The metabolic reconfiguration includes an increase in glucose uptake and fermentation, at the expense of respiration and oxidative phosphorylation (the Warburg effect), and involves a broad reconfiguration of nucleotide and amino acid metabolism. Both in yeast and humans, the regulation of this process seems to have a central player, PK, which is up-regulated in cancer, and to occur mostly on a post-transcriptional and post-translational basis. Furthermore, BIT allows to generate selectable translocation-derived recombinants (“translocants”), between any two desired chromosomal locations, in wild-type yeast strains transformed with a linear DNA cassette carrying a selectable marker flanked by two DNA sequences homologous to different chromosomes. Using the BIT system, targeted non-reciprocal translocations in mitosis are easily inducible. An extensive collection of different yeast translocants exhibiting genome instability and aberrant phenotypes similar to cancer cells has been produced and subjected to analysis. In this review, we hence provide an overview upon two yeast cancer models, and extrapolate general principles for mimicking human disease mechanisms in yeast.

  15. A smartphone-based pain management app for adolescents with cancer: establishing system requirements and a pain care algorithm based on literature review, interviews, and consensus.

    Jibb, Lindsay A; Stevens, Bonnie J; Nathan, Paul C; Seto, Emily; Cafazzo, Joseph A; Stinson, Jennifer N

    2014-03-19

    Pain that occurs both within and outside of the hospital setting is a common and distressing problem for adolescents with cancer. The use of smartphone technology may facilitate rapid, in-the-moment pain support for this population. To ensure the best possible pain management advice is given, evidence-based and expert-vetted care algorithms and system design features, which are designed using user-centered methods, are required. To develop the decision algorithm and system requirements that will inform the pain management advice provided by a real-time smartphone-based pain management app for adolescents with cancer. A systematic approach to algorithm development and system design was utilized. Initially, a comprehensive literature review was undertaken to understand the current body of knowledge pertaining to pediatric cancer pain management. A user-centered approach to development was used as the results of the review were disseminated to 15 international experts (clinicians, scientists, and a consumer) in pediatric pain, pediatric oncology and mHealth design, who participated in a 2-day consensus conference. This conference used nominal group technique to develop consensus on important pain inputs, pain management advice, and system design requirements. Using data generated at the conference, a prototype algorithm was developed. Iterative qualitative testing was conducted with adolescents with cancer, as well as pediatric oncology and pain health care providers to vet and refine the developed algorithm and system requirements for the real-time smartphone app. The systematic literature review established the current state of research related to nonpharmacological pediatric cancer pain management. The 2-day consensus conference established which clinically important pain inputs by adolescents would require action (pain management advice) from the app, the appropriate advice the app should provide to adolescents in pain, and the functional requirements of the app

  16. Combination of Estrogen and Immunosuppressive Agents to Establish a Mouse Model of Candidiasis with Concurrent Oral and Vaginal Mucosal Infection.

    Wang, Le; Wang, Chong; Mei, Huan; Shen, Yongnian; Lv, Guixia; Zeng, Rong; Zhan, Ping; Li, Dongmei; Liu, Weida

    2016-02-01

    Mouse model is an appropriate tool for pathogenic determination and study of host defenses during the fungal infection. Here, we established a mouse model of candidiasis with concurrent oral and vaginal mucosal infection. Two C. albicans strains sourced from clinical candidemia (SC5314) and mucosal infection (ATCC62342) were tested in ICR mice. The different combinational panels covering estrogen and immunosuppressive agents, cortisone, prednisolone and cyclophosphamide were used for concurrent oral and vaginal candidiasis establishment. Prednisolone in combination with estrogen proved an optimal mode for concurrent mucosal infection establishment. The model maintained for 1 week with fungal burden reached at least 10(5) cfu/g of tissue. This mouse model was evaluated by in vivo pharmacodynamics of fluconazole and host mucosal immunity of IL-17 and IL-23. Mice infected by SC5314 were cured by fluconazole. An increase in IL-23 in both oral and vaginal homogenates was observed after infection, while IL-17 only had a prominent elevation in oral tissue. This model could properly mimic complicated clinical conditions and provides a valuable means for antifungal assay in vivo and may also provide a useful method for the evaluation of host-fungal interactions.

  17. Cancer susceptibility and reproductive trade-offs: a model of the evolution of cancer defences.

    Boddy, Amy M; Kokko, Hanna; Breden, Felix; Wilkinson, Gerald S; Aktipis, C Athena

    2015-07-19

    The factors influencing cancer susceptibility and why it varies across species are major open questions in the field of cancer biology. One underexplored source of variation in cancer susceptibility may arise from trade-offs between reproductive competitiveness (e.g. sexually selected traits, earlier reproduction and higher fertility) and cancer defence. We build a model that contrasts the probabilistic onset of cancer with other, extrinsic causes of mortality and use it to predict that intense reproductive competition will lower cancer defences and increase cancer incidence. We explore the trade-off between cancer defences and intraspecific competition across different extrinsic mortality conditions and different levels of trade-off intensity, and find the largest effect of competition on cancer in species where low extrinsic mortality combines with strong trade-offs. In such species, selection to delay cancer and selection to outcompete conspecifics are both strong, and the latter conflicts with the former. We discuss evidence for the assumed trade-off between reproductive competitiveness and cancer susceptibility. Sexually selected traits such as ornaments or large body size require high levels of cell proliferation and appear to be associated with greater cancer susceptibility. Similar associations exist for female traits such as continuous egg-laying in domestic hens and earlier reproductive maturity. Trade-offs between reproduction and cancer defences may be instantiated by a variety of mechanisms, including higher levels of growth factors and hormones, less efficient cell-cycle control and less DNA repair, or simply a larger number of cell divisions (relevant when reproductive success requires large body size or rapid reproductive cycles). These mechanisms can affect intra- and interspecific variation in cancer susceptibility arising from rapid cell proliferation during reproductive maturation, intrasexual competition and reproduction. © 2015 The Author

  18. Reducing Societal Obesity: Establishing a Separate Exercise Model through Studies of Group Behavior.

    Puterbaugh, J S

    2016-01-01

    The past 50 years has brought attention to high and increasing levels of human obesity in most of the industrialized world. The medical profession has noticed, has evaluated, and has developed models for studying, preventing, and reversing obesity. The current model prescribes activity in specific quantities such as days, minutes, heart rates, and footfalls. Although decreased levels of activity have come from changes revolving around built environments and social networks, the existing medical model to lower body weights by increasing activity remains individually prescriptive. It is not working. The study of societal obesity precludes the individual and must involve group behavioral studies. Such studies necessitate acquiring separate tools and, therefore, require a significant change in the evaluation and treatment of obesity. Finding groups with common activities and lower levels of obesity would allow the development of new models of land use and encourage active lifestyles through shared interests.

  19. Promoter or enhancer, what's the difference? Deconstruction of established distinctions and presentation of a unifying model

    Andersson, Robin

    2015-01-01

    Gene transcription is strictly controlled by the interplay of regulatory events at gene promoters and gene-distal regulatory elements called enhancers. Despite extensive studies of enhancers, we still have a very limited understanding of their mechanisms of action and their restricted spatio......-temporal activities. A better understanding would ultimately lead to fundamental insights into the control of gene transcription and the action of regulatory genetic variants involved in disease. Here, I review and discuss pros and cons of state-of-the-art genomics methods to localize and infer the activity...... of enhancers. Among the different approaches, profiling of enhancer RNAs yields the highest specificity and may be superior in detecting in vivo activity. I discuss their apparent similarities to promoters, which challenge the established view of enhancers and promoters as distinct entities, and present...

  20. Modeling timelines for translational science in cancer; the impact of technological maturation

    McNamee, Laura M.; Ledley, Fred D.

    2017-01-01

    This work examines translational science in cancer based on theories of innovation that posit a relationship between the maturation of technologies and their capacity to generate successful products. We examined the growth of technologies associated with 138 anticancer drugs using an analytical model that identifies the point of initiation of exponential growth and the point at which growth slows as the technology becomes established. Approval of targeted and biological products corresponded ...

  1. Predictive model for survival in patients with gastric cancer.

    Goshayeshi, Ladan; Hoseini, Benyamin; Yousefli, Zahra; Khooie, Alireza; Etminani, Kobra; Esmaeilzadeh, Abbas; Golabpour, Amin

    2017-12-01

    Gastric cancer is one of the most prevalent cancers in the world. Characterized by poor prognosis, it is a frequent cause of cancer in Iran. The aim of the study was to design a predictive model of survival time for patients suffering from gastric cancer. This was a historical cohort conducted between 2011 and 2016. Study population were 277 patients suffering from gastric cancer. Data were gathered from the Iranian Cancer Registry and the laboratory of Emam Reza Hospital in Mashhad, Iran. Patients or their relatives underwent interviews where it was needed. Missing values were imputed by data mining techniques. Fifteen factors were analyzed. Survival was addressed as a dependent variable. Then, the predictive model was designed by combining both genetic algorithm and logistic regression. Matlab 2014 software was used to combine them. Of the 277 patients, only survival of 80 patients was available whose data were used for designing the predictive model. Mean ?SD of missing values for each patient was 4.43?.41 combined predictive model achieved 72.57% accuracy. Sex, birth year, age at diagnosis time, age at diagnosis time of patients' family, family history of gastric cancer, and family history of other gastrointestinal cancers were six parameters associated with patient survival. The study revealed that imputing missing values by data mining techniques have a good accuracy. And it also revealed six parameters extracted by genetic algorithm effect on the survival of patients with gastric cancer. Our combined predictive model, with a good accuracy, is appropriate to forecast the survival of patients suffering from Gastric cancer. So, we suggest policy makers and specialists to apply it for prediction of patients' survival.

  2. Neuromuscular interfacing: establishing an EMG-driven model for the human elbow joint.

    Pau, James W L; Xie, Shane S Q; Pullan, Andrew J

    2012-09-01

    Assistive devices aim to mitigate the effects of physical disability by aiding users to move their limbs or by rehabilitating through therapy. These devices are commonly embodied by robotic or exoskeletal systems that are still in development and use the electromyographic (EMG) signal to determine user intent. Not much focus has been placed on developing a neuromuscular interface (NI) that solely relies on the EMG signal, and does not require modifications to the end user's state to enhance the signal (such as adding weights). This paper presents the development of a flexible, physiological model for the elbow joint that is leading toward the implementation of an NI, which predicts joint motion from EMG signals for both able-bodied and less-abled users. The approach uses musculotendon models to determine muscle contraction forces, a proposed musculoskeletal model to determine total joint torque, and a kinematic model to determine joint rotational kinematics. After a sensitivity analysis and tuning using genetic algorithms, subject trials yielded an average root-mean-square error of 6.53° and 22.4° for a single cycle and random cycles of movement of the elbow joint, respectively. This helps us to validate the elbow model and paves the way toward the development of an NI.

  3. Identification of Luminal Breast Cancers that Establish a Tumor Supportive Macroenvironment Defined by Pro-Angiogenic Platelets and Bone Marrow Derived Cells

    Kuznetsov, Hanna S.; Marsh, Timothy; Markens, Beth A.; Castaño, Zafira; Greene-Colozzi, April; Hay, Samantha A.; Brown, Victoria E.; Richardson, Andrea L.; Signoretti, Sabina; Battinelli, Elisabeth M.; McAllister, Sandra S.

    2012-01-01

    Breast cancer recurrence rates vary following treatment, suggesting that tumor cells disseminate early from primary sites but remain indolent indefinitely before progressing to symptomatic disease. The reasons why some indolent disseminated tumors erupt into overt disease are unknown. We discovered a novel process by which certain luminal breast cancer cells and patient tumor specimens (LBC “instigators”) establish a systemic macroenvironment that supports outgrowth of otherwise-indolent disseminated tumors (“responders”). Instigating LBCs secrete cytokines that are absorbed by platelets, which are recruited to responding tumor sites where they aid vessel formation. Instigator-activated bone marrow cells (BMCs) enrich responding tumor cell expression of CD24, an adhesion molecule for platelets, and provide a source of VEGFR2+ tumor vessel cells. This cascade results in growth of responder adenocarcinomas and is abolished when platelet activation is inhibited by aspirin. These findings highlight the macroenvironment as an important component of disease progression that can be exploited therapeutically. PMID:22896036

  4. Modeling human papillomavirus and cervical cancer in the United States for analyses of screening and vaccination

    Ortendahl Jesse

    2007-10-01

    Full Text Available Abstract Background To provide quantitative insight into current U.S. policy choices for cervical cancer prevention, we developed a model of human papillomavirus (HPV and cervical cancer, explicitly incorporating uncertainty about the natural history of disease. Methods We developed a stochastic microsimulation of cervical cancer that distinguishes different HPV types by their incidence, clearance, persistence, and progression. Input parameter sets were sampled randomly from uniform distributions, and simulations undertaken with each set. Through systematic reviews and formal data synthesis, we established multiple epidemiologic targets for model calibration, including age-specific prevalence of HPV by type, age-specific prevalence of cervical intraepithelial neoplasia (CIN, HPV type distribution within CIN and cancer, and age-specific cancer incidence. For each set of sampled input parameters, likelihood-based goodness-of-fit (GOF scores were computed based on comparisons between model-predicted outcomes and calibration targets. Using 50 randomly resampled, good-fitting parameter sets, we assessed the external consistency and face validity of the model, comparing predicted screening outcomes to independent data. To illustrate the advantage of this approach in reflecting parameter uncertainty, we used the 50 sets to project the distribution of health outcomes in U.S. women under different cervical cancer prevention strategies. Results Approximately 200 good-fitting parameter sets were identified from 1,000,000 simulated sets. Modeled screening outcomes were externally consistent with results from multiple independent data sources. Based on 50 good-fitting parameter sets, the expected reductions in lifetime risk of cancer with annual or biennial screening were 76% (range across 50 sets: 69–82% and 69% (60–77%, respectively. The reduction from vaccination alone was 75%, although it ranged from 60% to 88%, reflecting considerable parameter

  5. GIS-based methods for establishing the datafoundation for traffic models

    Nielsen, Otto Anker

    1997-01-01

    Traffic models demand large amounts of data - some of which are: Traffic network topology, traffic network data, zone-data and trip matrices. GIS is a natural tool for handling most of these data as it can ease the work process and improve the quality control. However, traffic models demand a com......-plex topology not very well covered by the traditional GIS-topology. The paper describes a number of applications where ARC/INFO and ArcView have been used to automate the process of building a traffic network topology. The methodology has been used on a number of full-scale models, from medium sized urban...... areas to metropolitan areas (Copenhagen, Denmark and Bandung, Indonesia). The paper covers key subjects in the work process which has been eased considerably by using AML and Avenue scripts or by using the information from ARC/INFO in external applications:· Semi-automatic procedures for attaching zones...

  6. Establishing a small animal model for evaluating protective immunity against mumps virus.

    Adrian Pickar

    Full Text Available Although mumps vaccines have been used for several decades, protective immune correlates have not been defined. Recently, mumps outbreaks have occurred in vaccinated populations. To better understand the causes of the outbreaks and to develop means to control outbreaks in mumps vaccine immunized populations, defining protective immune correlates will be critical. Unfortunately, no small animal model for assessing mumps immunity exists. In this study, we evaluated use of type I interferon (IFN alpha/beta receptor knockout mice (IFN-α/βR-/- for such a model. We found these mice to be susceptible to mumps virus administered intranasally and intracranially. Passive transfer of purified IgG from immunized mice protected naïve mice from mumps virus infection, confirming the role of antibody in protection and demonstrating the potential for this model to evaluate mumps immunity.

  7. Interests and limits of epidemiology for the evaluation of risks of radiation induced cancer and the establishing of radiation protection standards

    Hubert, D.

    1991-04-01

    Epidemiological studies allow to confirm that a risk does exist for some types of cancer following high-dose exposures often at high dose-rates. However, no conclusion can be drawn for low doses and low dose-rates. Therefore we have to extrapolate from known high-dose risks to low doses and low dose-rates by various dose-response patterns. Another difficulty in assessing radiation cancer risks comes from the long latency time, which explains that all excess cancers have not yet been observed in the irradiated population studied. Once more, mathematical models are used to project excess lifetime cancer mortality. The estimations of radiation cancer risks are therefore marked by a great number of uncertainties, since they change accordingly to the model used. Other uncertainties come from the data, especially the dose estimates and are heightened when extrapolating to other populations. In 1988, UNSCEAR assessed new estimates for excess lifetime cancer mortality in the range of 4 to 11% per gray. These values mean a revaluation of the previous estimates by a 1.6 to 4.4 factor, which is mainly consecutive to the use of different projection models. Besides, they are solely based on the Hiroshima and Nagasaki survivors, whereas patient studies assess a lower risk. Finally UNSCEAR does not precisely state what is the available reduction factor to modify risks for low doses and low dose rates which should lie between 2 and 10. Due to a number of persistent uncertainties, we should not consider it justified to revise protection standards presently. (author)

  8. ESTABLISHING A NATIONAL 3D GEO-DATA MODEL FOR BUILDING DATA COMPLIANT TO CITYGML: CASE OF TURKEY

    S. Ates Aydar

    2016-06-01

    Full Text Available This paper presents the generation of the 3D national building geo-data model of Turkey, which is compatible with the international OGC CityGML Encoding Standard. We prepare an ADE named CityGML-TRKBIS.BI that is produced by extending existing thematic modules of CityGML according to TRKBIS needs. All thematic data groups in TRKBIS geo-data model have been remodelled in order to generate the national large scale 3D geo-data model for Turkey. Specific attention has been paid to data groups that have different class structure according to related CityGML data themes such as building data model. Current 2D geo-information model for building data theme of Turkey (TRKBIS.BI was established based on INSPIRE specifications for building (Core 2D and Extended 2D profiles, ISO/TC 211 standards and OGC web services. New version of TRKBIS.BI which is established according to semantic and geometric rules of CityGML will represent 2D-2.5D and 3D objects. After a short overview on generic approach, this paper describes extending CityGML building data theme according to TRKBIS.BI through several steps. First, building models of both standards were compared according to their data structure, classes and attributes. Second, CityGML building model was extended with respect to TRKBIS needs and CityGML-TRKBIS Building ADE was established in UML. This study provides new insights into 3D applications in Turkey. The generated 3D geo-data model for building thematic class will be used as a common exchange format that meets 2D, 2.5D and 3D implementation needs at national level.

  9. Towards the establishment of a porcine model to study human amebiasis.

    Fabienne Girard-Misguich

    Full Text Available BACKGROUND: Entamoeba histolytica is an important parasite of the human intestine. Its life cycle is monoxenous with two stages: (i the trophozoite, growing in the intestine and (ii the cyst corresponding to the dissemination stage. The trophozoite in the intestine can live as a commensal leading to asymptomatic infection or as a tissue invasive form producing mucosal ulcers and liver abscesses. There is no animal model mimicking the whole disease cycle. Most of the biological information on E. histolytica has been obtained from trophozoite adapted to axenic culture. The reproduction of intestinal amebiasis in an animal model is difficult while for liver amebiasis there are well-described rodent models. During this study, we worked on the assessment of pigs as a new potential model to study amebiasis. METHODOLOGY/PRINCIPAL FINDINGS: We first co-cultured trophozoites of E. histolytica with porcine colonic fragments and observed a disruption of the mucosal architecture. Then, we showed that outbred pigs can be used to reproduce some lesions associated with human amebiasis. A detailed analysis was performed using a washed closed-jejunal loops model. In loops inoculated with virulent amebas a severe acute ulcerative jejunitis was observed with large hemorrhagic lesions 14 days post-inoculation associated with the presence of the trophozoites in the depth of the mucosa in two out four animals. Furthermore, typical large sized hepatic abscesses were observed in the liver of one animal 7 days post-injection in the portal vein and the liver parenchyma. CONCLUSIONS: The pig model could help with simultaneously studying intestinal and extraintestinal lesion development.

  10. Modelling breast cancer tumour growth for a stable disease population.

    Isheden, Gabriel; Humphreys, Keith

    2017-01-01

    Statistical models of breast cancer tumour progression have been used to further our knowledge of the natural history of breast cancer, to evaluate mammography screening in terms of mortality, to estimate overdiagnosis, and to estimate the impact of lead-time bias when comparing survival times between screen detected cancers and cancers found outside of screening programs. Multi-state Markov models have been widely used, but several research groups have proposed other modelling frameworks based on specifying an underlying biological continuous tumour growth process. These continuous models offer some advantages over multi-state models and have been used, for example, to quantify screening sensitivity in terms of mammographic density, and to quantify the effect of body size covariates on tumour growth and time to symptomatic detection. As of yet, however, the continuous tumour growth models are not sufficiently developed and require extensive computing to obtain parameter estimates. In this article, we provide a detailed description of the underlying assumptions of the continuous tumour growth model, derive new theoretical results for the model, and show how these results may help the development of this modelling framework. In illustrating the approach, we develop a model for mammography screening sensitivity, using a sample of 1901 post-menopausal women diagnosed with invasive breast cancer.

  11. Establishment and analysis of coupled dynamic model for dual-mass silicon micro-gyroscope

    Wang, Zhanghui; Qiu, Anping; Shi, Qin; Zhang, Taoyuan

    2017-12-01

    This paper presents a coupled dynamic model for a dual-mass silicon micro-gyroscope (DMSG). It can quantitatively analyze the influence of left-right stiffness difference on the natural frequencies, modal matrix and modal coupling coefficient of the DMSG. The analytic results are verified by using the finite element method (FEM) simulation. The model shows that with the left-right stiffness difference of 1%, the modal coupling coefficient is 12% in the driving direction and 31% in the sensing direction. It also shows that in order to achieve good separation, the stiffness of base beam should be small enough in both the driving and sensing direction.

  12. Preclinical Murine Models for Lung Cancer: Clinical Trial Applications

    Amelia Kellar

    2015-01-01

    Full Text Available Murine models for the study of lung cancer have historically been the backbone of preliminary preclinical data to support early human clinical trials. However, the availability of multiple experimental systems leads to debate concerning which model, if any, is best suited for a particular therapeutic strategy. It is imperative that these models accurately predict clinical benefit of therapy. This review provides an overview of the current murine models used to study lung cancer and the advantages and limitations of each model, as well as a retrospective evaluation of the uses of each model with respect to accuracy in predicting clinical benefit of therapy. A better understanding of murine models and their uses, as well as their limitations may aid future research concerning the development and implementation of new targeted therapies and chemotherapeutic agents for lung cancer.

  13. Cancer-initiating cells derived from established cervical cell lines exhibit stem-cell markers and increased radioresistance

    López, Jacqueline; Poitevin, Adela; Mendoza-Martínez, Veverly; Pérez-Plasencia, Carlos; García-Carrancá, Alejandro

    2012-01-01

    Cancer-initiating cells (CICs) are proposed to be responsible for the generation of metastasis and resistance to therapy. Accumulating evidences indicates CICs are found among different human cancers and cell lines derived from them. Few studies address the characteristics of CICs in cervical cancer. We identify biological features of CICs from four of the best-know human cell lines from uterine cervix tumors. (HeLa, SiHa, Ca Ski, C-4 I). Cells were cultured as spheres under stem-cell conditions. Flow cytometry was used to detect expression of CD34, CD49f and CD133 antigens and Hoechst 33342 staining to identify side population (SP). Magnetic and fluorescence-activated cell sorting was applied to enrich and purify populations used to evaluate tumorigenicity in nude mice. cDNA microarray analysis and in vitro radioresistance assay were carried out under standard conditions. CICs, enriched as spheroids, were capable to generate reproducible tumor phenotypes in nu-nu mice and serial propagation. Injection of 1 × 10 3 dissociated spheroid cells induced tumors in the majority of animals, whereas injection of 1 × 10 5 monolayer cells remained nontumorigenic. Sphere-derived CICs expressed CD49f surface marker. Gene profiling analysis of HeLa and SiHa spheroid cells showed up-regulation of CICs markers characteristic of the female reproductive system. Importantly, epithelial to mesenchymal (EMT) transition-associated markers were found highly expressed in spheroid cells. More importantly, gene expression analysis indicated that genes required for radioresistance were also up-regulated, including components of the double-strand break (DSB) DNA repair machinery and the metabolism of reactive oxygen species (ROS). Dose-dependent radiation assay indicated indeed that CICs-enriched populations exhibit an increased resistance to ionizing radiation (IR). We characterized a self-renewing subpopulation of CICs found among four well known human cancer-derived cell lines (HeLa, Si

  14. School Factors Explaining Achievement on Cognitive and Affective Outcomes : Establishing a Dynamic Model of Educational Effectiveness

    Creemers, Bert; Kyriakides, Leonidas

    2010-01-01

    The dynamic model of educational effectiveness defines school level factors associated with student outcomes. Emphasis is given to the two main aspects of policy, evaluation, and improvement in schools which affect quality of teaching and learning at both the level of teachers and students: a)

  15. Establishing a Reproducible Hypertrophic Scar following Thermal Injury: A Porcine Model

    Scott J. Rapp, MD

    2015-02-01

    Conclusions: Deep partial-thickness thermal injury to the back of domestic swine produces an immature hypertrophic scar by 10 weeks following burn with thickness appearing to coincide with the location along the dorsal axis. With minimal pig to pig variation, we describe our technique to provide a testable immature scar model.

  16. Extraction and identification of mixed pesticides’ Raman signal and establishment of their prediction models

    A nondestructive and sensitive method was developed to detect the presence of mixed pesticides of acetamiprid, chlorpyrifos and carbendazim on apples by surface-enhanced Raman spectroscopy (SERS). Self-modeling mixture analysis (SMA) was used to extract and identify the Raman spectra of individual p...

  17. Establishing an Educational Game Development Model: From the Experience of Teaching Search Engine Optimization

    Lui, Richard W. C.; Au, Cheuk Hang

    2018-01-01

    This article describes how different literatures have suggested the positive role of educational games in students' learning, but it can be hard to find an existing game for student learning. Some lecturers may try to develop a game for their courses, but there were not many effective models for educational board game development. The authors have…

  18. Human factors science and safety engineering : can the STAMP model serve in establishing a common language?

    Karanikas, Nektarios; Schwarz, M; Harfmann, J

    2017-01-01

    A symbiotic relationship between human factors and safety scientists is needed to ensure the provision of holistic solutions for problems emerging in modern socio-technical systems. System Theoretic Accident Model and Processes (STAMP) tackles both interactions and individual failures of human and

  19. Application of three-dimensional reconstruction technology in establishment of atlas space model and sex determination

    Zhou Jianying; Tian Yong; He Qing; Li Youqiong; Han Qing; Cheng Kailiang

    2013-01-01

    Objective: To establish the method of using the atlas morphological indexes for sex determination in Jilin province and to evaluate its effect. Methods: The clinic neck CT images were used to reconstruct the 3D image of atlas. A total of 27 linear measurement on 8 aspects of the atlas were measured and the ratios were calculated. The 14 items were selected. Results: Of the total 27 linear measurements, 14 were sexually dimorphic (P<0.05), and the accuracies of sex determination of 27 indexes were 52.0% -89.3% . The highest accuracy was width of vertebral body (86.7% ). A function with variables predicting sex with 96.8% accuracy was derived by using stepwise method of discriminant function analysis: Y=1.308W - 0.409CDF - 0.469LTPSD - 0.849LUACD + 0.478RUACD + 0.332RDACD + 0.363ATH - 0.334PTH - 0.236PAL. Conclusion: The method of using atlas traits for sex determination in Jilin province is practicable. (authors)

  20. A TOE Approach to Establish a Green Supply Chain Adoption Decision Model in the Semiconductor Industry

    Bang-Ning Hwang

    2016-02-01

    Full Text Available The green supply chain is an innovation that extends traditional sustainability initiatives to environmental activities in the supply chain and aims to minimize a product’s environmental impact throughout its life cycle. The adoption of a green supply chain involves a complex decision-making process characterized by multiple criteria. The goal of the current study is to construct a decision framework by identifying a comprehensive set of consideration factors and their causal relationships. The consideration factors are deliberately drawn from a variety of different, yet related, theories and are grouped into an extensive Technology-Organization -Environment (TOE framework. In accordance with the Decision Making Trial and Evaluation Laboratory (DEMATEL method, the decision framework was analyzed for appropriateness through surveys of selected experts in the semiconductor industry. Because the semiconductor industry has a long history of heavy resource usage and has proven an early advocate of green supply chains, results from this study can provide insights to other firms with similar operations and aims. The contributions of this research are twofold. First, its theoretical contribution consists of integrating previously separate strands of different theories into a holistic framework and exploring the causal relationships among decision factors. Second, its practical contribution lies in its establishment of a strategic path that provides firms a set of priorities when adopting green supply chains.

  1. Established Models and New Paradigms for Hypoxia-Driven Cancer-Associated Bone Disease

    Cox, Thomas R.; Erler, Janine T.; Rumney, Robin M.H.

    2018-01-01

    -driven effects in the primary tumour are wide ranging including changes in gene expression, dysregulation of signalling pathways, resistance to chemotherapy, neovascularisation, increased tumour cell proliferation and migration. Paget’s seed and soil theory states that for a metastasising tumour cell ‘the seed...... metastases. This review describes the roles of hypoxia in primary tumour progression to metastasis, with a focus on key signalling pathways and treatment options to reduce patient morbidity and increase survival....

  2. Gompertzian stochastic model with delay effect to cervical cancer growth

    Mazlan, Mazma Syahidatul Ayuni binti; Rosli, Norhayati binti; Bahar, Arifah

    2015-01-01

    In this paper, a Gompertzian stochastic model with time delay is introduced to describe the cervical cancer growth. The parameters values of the mathematical model are estimated via Levenberg-Marquardt optimization method of non-linear least squares. We apply Milstein scheme for solving the stochastic model numerically. The efficiency of mathematical model is measured by comparing the simulated result and the clinical data of cervical cancer growth. Low values of Mean-Square Error (MSE) of Gompertzian stochastic model with delay effect indicate good fits

  3. Gompertzian stochastic model with delay effect to cervical cancer growth

    Mazlan, Mazma Syahidatul Ayuni binti; Rosli, Norhayati binti [Faculty of Industrial Sciences and Technology, Universiti Malaysia Pahang, Lebuhraya Tun Razak, 26300 Gambang, Pahang (Malaysia); Bahar, Arifah [Department of Mathematical Sciences, Faculty of Science, Universiti Teknologi Malaysia, 81310 Johor Bahru, Johor and UTM Centre for Industrial and Applied Mathematics (UTM-CIAM), Universiti Teknologi Malaysia, 81310 Johor Bahru, Johor (Malaysia)

    2015-02-03

    In this paper, a Gompertzian stochastic model with time delay is introduced to describe the cervical cancer growth. The parameters values of the mathematical model are estimated via Levenberg-Marquardt optimization method of non-linear least squares. We apply Milstein scheme for solving the stochastic model numerically. The efficiency of mathematical model is measured by comparing the simulated result and the clinical data of cervical cancer growth. Low values of Mean-Square Error (MSE) of Gompertzian stochastic model with delay effect indicate good fits.

  4. Risk prediction models for selection of lung cancer screening candidates: A retrospective validation study.

    Kevin Ten Haaf

    2017-04-01

    Full Text Available Selection of candidates for lung cancer screening based on individual risk has been proposed as an alternative to criteria based on age and cumulative smoking exposure (pack-years. Nine previously established risk models were assessed for their ability to identify those most likely to develop or die from lung cancer. All models considered age and various aspects of smoking exposure (smoking status, smoking duration, cigarettes per day, pack-years smoked, time since smoking cessation as risk predictors. In addition, some models considered factors such as gender, race, ethnicity, education, body mass index, chronic obstructive pulmonary disease, emphysema, personal history of cancer, personal history of pneumonia, and family history of lung cancer.Retrospective analyses were performed on 53,452 National Lung Screening Trial (NLST participants (1,925 lung cancer cases and 884 lung cancer deaths and 80,672 Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial (PLCO ever-smoking participants (1,463 lung cancer cases and 915 lung cancer deaths. Six-year lung cancer incidence and mortality risk predictions were assessed for (1 calibration (graphically by comparing the agreement between the predicted and the observed risks, (2 discrimination (area under the receiver operating characteristic curve [AUC] between individuals with and without lung cancer (death, and (3 clinical usefulness (net benefit in decision curve analysis by identifying risk thresholds at which applying risk-based eligibility would improve lung cancer screening efficacy. To further assess performance, risk model sensitivities and specificities in the PLCO were compared to those based on the NLST eligibility criteria. Calibration was satisfactory, but discrimination ranged widely (AUCs from 0.61 to 0.81. The models outperformed the NLST eligibility criteria over a substantial range of risk thresholds in decision curve analysis, with a higher sensitivity for all models and a

  5. Inhibitory effect of gene combination in a mouse model of colon cancer with liver metastasis.

    DU, Tong; Niu, Hongxin

    2014-09-01

    The aim of the present study was to establish an animal liver metastasis model with human colon cancer and investigate the inhibitory effect of the wild type (WT) p53 gene combined with thymidine kinase/ganciclovir (TK/GCV) and cytosine deaminase/5-fluorocytosine (CD/5-FC) systems on liver metastasis of colon cancer. A nude mouse liver metastasis model with human colon cancer was established via a spleen cultivation method. A total of 32 nude mice were randomly divided into four groups, each group with eight mice. Group 1 mice received splenic injections of SW480 cells (control group), while group 2 mice were injected with SW480/p53 cells in the spleen. Group 3 mice were administered splenic injections of SW480/TK-CD cells, and GCV and 5-FC were injected into the abdominal cavity. Finally, group 4 mice received splenic injections of SW480/p53 cells mixed in equal proportion with SW480/TK-CD cells, as well as GCV and 5-FC injections in the abdominal cavity. These cells described were constructed in our laboratory and other laboratories. The number of liver metastatic tumors, the liver metastasis rate, conventional pathology, electron microscopy and other indicators in the nude mice of each group were compared and observed. The nude mouse liver metastasis model with human colon cancer was successfully established; the liver metastasis rate of the control group was 100%. The results demonstrated that the rate of liver metastasis in the nude mice in each treatment group decreased, as well as the average number of liver metastatic tumors. Furthermore, the effect of the treatment group with genetic combination (group 4) was the most effective, demonstrating that WTp53 had a synergistic effect with TK/GCV and CD/5-FC. Therefore, the present study successfully established a mouse model of liver metastasis with colon cancer by injecting human colon cancer cells in the spleen. Combined gene therapy was shown to have a synergistic effect, which effectively inhibited the

  6. Modeling cancer registration processes with an enhanced activity diagram.

    Lyalin, D; Williams, W

    2005-01-01

    Adequate instruments are needed to reflect the complexity of routine cancer registry operations properly in a business model. The activity diagram is a key instrument of the Unified Modeling Language (UML) for the modeling of business processes. The authors aim to improve descriptions of processes in cancer registration, as well as in other public health domains, through the enhancements of an activity diagram notation within the standard semantics of UML. The authors introduced the practical approach to enhance a conventional UML activity diagram, complementing it with the following business process concepts: timeline, duration for individual activities, responsibilities for individual activities within swimlanes, and descriptive text. The authors used an enhanced activity diagram for modeling surveillance processes in the cancer registration domain. Specific example illustrates the use of an enhanced activity diagram to visualize a process of linking cancer registry records with external mortality files. Enhanced activity diagram allows for the addition of more business concepts to a single diagram and can improve descriptions of processes in cancer registration, as well as in other domains. Additional features of an enhanced activity diagram allow to advance the visualization of cancer registration processes. That, in turn, promotes the clarification of issues related to the process timeline, responsibilities for particular operations, and collaborations among process participants. Our first experiences in a cancer registry best practices development workshop setting support the usefulness of such an approach.

  7. White Adipose Tissue Cells Are Recruited by Experimental Tumors and Promote Cancer Progression in Mouse Models

    Zhang, Yan; Daquinag, Alexes; Traktuev, Dmitry O.; Amaya-Manzanares, Felipe; Simmons, Paul J.; March, Keith L.; Pasqualini, Renata; Arap, Wadih; Kolonin, Mikhail G.

    2010-01-01

    The connection between obesity and accelerated cancer progression has been established, but the mediating mechanisms are not well understood. We have shown that stromal cells from white adipose tissue (WAT) cooperate with the endothelium to promote blood vessel formation through the secretion of soluble trophic factors. Here, we hypothesize that WAT directly mediates cancer progression by serving as a source of cells that migrate to tumors and promote neovascularization. To test this hypothesis, we have evaluated the recruitment of WAT-derived cells by tumors and the effect of their engraftment on tumor growth by integrating a transgenic mouse strain engineered for expansion of traceable cells with established allograft and xenograft cancer models. Our studies show that entry of adipose stromal and endothelial cells into systemic circulation leads to their homing to and engraftment into tumor stroma and vasculature, respectively. We show that recruitment of adipose stromal cells by tumors is sufficient to promote tumor growth. Finally, we show that migration of stromal and vascular progenitor cells from WAT grafts to tumors is also associated with acceleration of cancer progression. These results provide a biological insight for the clinical association between obesity and cancer, thus outlining potential avenues for preventive and therapeutic strategies. PMID:19491274

  8. Renewable Energy Cost Modeling. A Toolkit for Establishing Cost-Based Incentives in the United States

    Gifford, Jason S. [Sustainable Energy Advantage, LLC, Framington, MA (United States); Grace, Robert C. [Sustainable Energy Advantage, LLC, Framington, MA (United States); Rickerson, Wilson H. [Meister Consultants Group, Inc., Boston, MA (United States)

    2011-05-01

    This report serves as a resource for policymakers who wish to learn more about levelized cost of energy (LCOE) calculations, including cost-based incentives. The report identifies key renewable energy cost modeling options, highlights the policy implications of choosing one approach over the other, and presents recommendations on the optimal characteristics of a model to calculate rates for cost-based incentives, FITs, or similar policies. These recommendations shaped the design of NREL's Cost of Renewable Energy Spreadsheet Tool (CREST), which is used by state policymakers, regulators, utilities, developers, and other stakeholders to assist with analyses of policy and renewable energy incentive payment structures. Authored by Jason S. Gifford and Robert C. Grace of Sustainable Energy Advantage LLC and Wilson H. Rickerson of Meister Consultants Group, Inc.

  9. A business model for the establishment of the European grid infrastructure

    Candiello, A; Cresti, D; Ferrari, T; Mazzucato, M; Perini, L

    2010-01-01

    An international grid has been built in Europe during the past years in the framework of various EC-funded projects to support the growth of e-Science. After several years of work spent to increase the scale of the infrastructure, to expand the user community and improve the availability of the services delivered, effort is now concentrating on the creation of a new organizational model, capable of fulfilling the vision of a sustainable European grid infrastructure. The European Grid Initiative (EGI) is the proposed framework to seamlessly link at a global level the European national grid e-Infrastructures operated by the National Grid Initiatives and European International Research Organizations, and based on a European Unified Middleware Distribution, which will be the result of a joint effort of various European grid Middleware Consortia. This paper describes the requirements that EGI addresses, the actors contributing to its foundation, the offering and the organizational structure that constitute the EGI business model.

  10. COMMENTS OF THE OCDE 2008MODEL CONVENTION ON ESTABLISHING THE TAX RESIDENCE

    Lect. Mihail Antonescu Ph. D; Ligia Antonescu Ph. D

    2010-01-01

    In the fiscal field, the competition between countries develops as a growing phenomenon, and results in the permanent improvement of the legislation to attract the investments and implicitly, the incomes to be taxed. Most developed countries set the limits of their tax jurisdiction, by defining the concept of resident. In the Romanian legislation, there are transposed the provisions of the OECD Model Convention on defining the residence, both in terms of residence and period of actual presenc...

  11. Establishment of infection models in zebrafish larvae (Danio rerio to study the pathogenesis of Aeromonas hydrophila.

    Paolo Roberto Saraceni

    2016-08-01

    Full Text Available Aeromonas hydrophila is a Gram-negative opportunistic pathogen of fish and terrestrial animals. In humans, A. hydrophila mainly causes gastroenteritis, septicaemia and tissue infections. The mechanisms of infection, the main virulence factors and the host immune response triggered by A. hydrophila have been studied in detail using murine models and adult fish. However, the great limitation of studying adult animals is that the animal must be sacrificed and its tissues/organs extracted, which prevents the study of the infectious processes in the whole living animal.Zebrafish larvae are being used for the analysis of several infectious diseases, but their use for studying the pathogenesis of A. hydrophila has never been explored. The great advantage of zebrafish larvae is their transparency during the first week after fertilization, which allows detailed descriptions of the infectious processes using in vivo imaging techniques such as differential interferential contrast (DIC and fluorescence microscopy. Moreover, the availability of fluorescent pathogens and transgenic reporter zebrafish lines expressing fluorescent immune cells, immune marker genes or cytokines/chemokines allows the host-pathogen interactions to be characterized.The present study explores the suitability of zebrafish larvae to study the pathogenesis of A. hydrophila and the interaction mechanisms between the bacterium and the innate immune responses through an infection model using different routes for infection. We used an early-embryo infection model at 3 days post-fertilization (dpf through the microinjection of A. hydrophila into the duct of Cuvier, caudal vein, notochord or muscle and two bath infection models using 4 dpf healthy and injured larvae. The latter resembled the natural conditions under which A. hydrophila produces infectious diseases in animals. We compared the cellular processes after infection in each anatomical site by confocal fluorescence imaging and

  12. Establishing a Proper Model of Tobacco Dependence: Influence of Age and Tobacco Smoke Constituents

    Gellner, Candice Ann

    2017-01-01

    Cigarette smoking is the leading preventable cause of death in the United States. Of those who smoke, 9 out of 10 report trying their first cigarette before the age of 18. Although most people who initiate tobacco use are teenagers, animal models for studying tobacco dependence have traditionally focused on how adult animals initiate, withdrawal from and relapse to cigarette smoking. Furthermore, cigarette smoke contains more than 7,000 constituents, including nicotine, yet pre-clinical resea...

  13. Experimental verification of dynamic radioecological models established after the Chernobyl reactor accident

    Voigt, G.; Mueller, H.; Proehl, G.; Stocke, H.; Paretzke, H.G.

    1991-01-01

    The experiments reported were carried out for a verification of existing, dynamic radioecological models, especially of the ECOSYS model. The database used for the verification covers the radioactivity concentrations of Cs-134, Cs-137, I-131 measured after the Chernobyl reactor accident in foodstuffs and environmental samples, the results of field experiments on radionuclide translocation after foliar uptake or absorption by the roots of edible plants. The measured data were compared with the model predictions for the radionuclides under review. The Cs-134 and Cs-137 translocation factors which describe the redistribution of these radionuclides in the plant after foliar uptake were experimentally determined by a single sprinkling with Chernobyl rainwater, and were measured to be the following as a function of sprinkling time: winter wheat, 0.002-0.13; spring wheat, 0.003-0.09; winter rye, 0.002-0.27; barley, 0.002-0.04; potatoes, 0.05-0.35; carrots, 0.02-0.07; bush beans, 0.04-0.3; cabbage, 0.1-0.5. The weathering half-life of the radionuclides in lettuce was determined to be ten days. Transfer factors determined for root absorption of Cs-137 were measured to be an average of 0.002 for grains, 0.002 for potatoes, 0.004 for white cabbage, 0.003 for bush beans and carrots, and 0.007 for lettuce. There was an agreement between the ECOSYS model predictions and the measured radioactivity concentrations of the corresponding radionuclides. (orig./HP) [de

  14. Establishment of imageable model of T-cell lymphoma growing in syngenic mice

    Větvička, David; Hovorka, Ondřej; Kovář, Lubomír; Říhová, Blanka

    2009-01-01

    Roč. 29, č. 11 (2009), s. 4513-4518 ISSN 0250-7005 R&D Projects: GA AV ČR IAA400200702; GA AV ČR KAN200200651; GA ČR GD310/08/H077 Institutional research plan: CEZ:AV0Z50200510 Keywords : Imageable model * EL-4 T- cell lymphoma * whole body imaging Subject RIV: EC - Immunology Impact factor: 1.428, year: 2009

  15. Differential effects of rapamycin and dexamethasone in mouse models of established allergic asthma.

    Elizabeth M Mushaben

    Full Text Available The mammalian target of rapamycin (mTOR plays an important role in cell growth/differentiation, integrating environmental cues, and regulating immune responses. Our lab previously demonstrated that inhibition of mTOR with rapamycin prevented house dust mite (HDM-induced allergic asthma in mice. Here, we utilized two treatment protocols to investigate whether rapamycin, compared to the steroid, dexamethasone, could inhibit allergic responses during the later stages of the disease process, namely allergen re-exposure and/or during progression of chronic allergic disease. In protocol 1, BALB/c mice were sensitized to HDM (three i.p. injections and administered two intranasal HDM exposures. After 6 weeks of rest/recovery, mice were re-exposed to HDM while being treated with rapamycin or dexamethasone. In protocol 2, mice were exposed to HDM for 3 or 6 weeks and treated with rapamycin or dexamethasone during weeks 4-6. Characteristic features of allergic asthma, including IgE, goblet cells, airway hyperreactivity (AHR, inflammatory cells, cytokines/chemokines, and T cell responses were assessed. In protocol 1, both rapamycin and dexamethasone suppressed goblet cells and total CD4(+ T cells including activated, effector, and regulatory T cells in the lung tissue, with no effect on AHR or total inflammatory cell numbers in the bronchoalveolar lavage fluid. Rapamycin also suppressed IgE, although IL-4 and eotaxin 1 levels were augmented. In protocol 2, both drugs suppressed total CD4(+ T cells, including activated, effector, and regulatory T cells and IgE levels. IL-4, eotaxin, and inflammatory cell numbers were increased after rapamycin and no effect on AHR was observed. Dexamethasone suppressed inflammatory cell numbers, especially eosinophils, but had limited effects on AHR. We conclude that while mTOR signaling is critical during the early phases of allergic asthma, its role is much more limited once disease is established.

  16. Establishing a laboratory model of dental unit waterlines bacterial biofilms using a CDC biofilm reactor.

    Yoon, Hye Young; Lee, Si Young

    2017-11-01

    In this study, a laboratory model to reproduce dental unit waterline (DUWL) biofilms was developed using a CDC biofilm reactor (CBR). Bacteria obtained from DUWLs were filtered and cultured in Reasoner's 2A (R2A) for 10 days, and were subsequently stored at -70°C. This stock was cultivated on R2A in batch mode. After culturing for five days, the bacteria were inoculated into the CBR. Biofilms were grown on polyurethane tubing for four days. Biofilm accumulation and thickness was 1.3 × 10 5  CFU cm -2 and 10-14 μm respectively, after four days. Bacteria in the biofilms included cocci and rods of short and medium lengths. In addition, 38 bacterial genera were detected in biofilms. In this study, the suitability and reproducibility of the CBR model for DUWL biofilm formation were demonstrated. The model provides a foundation for the development of bacterial control methods for DUWLs.

  17. Studies on kinetics of water quality factors to establish water transparency model in Neijiang River, China.

    Li, Ronghui; Pan, Wei; Guo, Jinchuan; Pang, Yong; Wu, Jianqiang; Li, Yiping; Pan, Baozhu; Ji, Yong; Ding, Ling

    2014-05-01

    The basis for submerged plant restoration in surface water is to research the complicated dynamic mechanism of water transparency. In this paper, through the impact factor analysis of water transparency, the suspended sediment, dissolved organic matter, algae were determined as three main impactfactors for water transparency of Neijiang River in Eastern China. And the multiple regression equation of water transparency and sediment concentration, permanganate index, chlorophyll-a concentration was developed. Considering the complicated transport and transformation of suspended sediment, dissolved organic matter and algae, numerical model of them were developed respectively for simulating the dynamic process. Water transparency numerical model was finally developed by coupling the sediment, water quality, and algae model. These results showed that suspended sediment was a key factor influencing water transparency of Neijiang River, the influence of water quality indicated by chemical oxygen demand and algal concentration indicated by chlorophyll a were indeterminate when their concentrations were lower, the influence was more obvious when high concentrations are available, such three factors showed direct influence on water transparency.

  18. Establishment of a new murine elastase-induced aneurysm model combined with transplantation.

    Zuzanna Rowinska

    Full Text Available The aim of our study was to develop a reproducible murine model of elastase-induced aneurysm formation combined with aortic transplantation.Adult male mice (n = 6-9 per group underwent infrarenal, orthotopic transplantation of the aorta treated with elastase or left untreated. Subsequently, both groups of mice were monitored by ultrasound until 7 weeks after grafting.Mice receiving an elastase-pretreated aorta developed aneurysms and exhibited a significantly increased diastolic vessel diameter compared to control grafted mice at 7 week after surgery (1.11 ± 0.10 mm vs. 0.75 ± 0.03 mm; p ≤ 0,001. Histopathological examination revealed disruption of medial elastin, an increase in collagen content and smooth muscle cells, and neointima formation in aneurysm grafts.We developed a reproducible murine model of elastase-induced aneurysm combined with aortic transplantation. This model may be suitable to investigate aneurysm-specific inflammatory processes and for use in gene-targeted animals.

  19. [Establish research model of post-marketing clinical safety evaluation for Chinese patent medicine].

    Zheng, Wen-ke; Liu, Zhi; Lei, Xiang; Tian, Ran; Zheng, Rui; Li, Nan; Ren, Jing-tian; Du, Xiao-xi; Shang, Hong-cai

    2015-09-01

    The safety of Chinese patent medicine has become a focus of social. It is necessary to carry out work on post-marketing clinical safety evaluation for Chinese patent medicine. However, there have no criterions to guide the related research, it is urgent to set up a model and method to guide the practice for related research. According to a series of clinical research, we put forward some views, which contained clear and definite the objective and content of clinical safety evaluation, the work flow should be determined, make a list of items for safety evaluation project, and put forward the three level classification of risk control. We set up a model of post-marketing clinical safety evaluation for Chinese patent medicine. Based this model, the list of items can be used for ranking medicine risks, and then take steps for different risks, aims to lower the app:ds:risksrisk level. At last, the medicine can be managed by five steps in sequence. The five steps are, collect risk signal, risk recognition, risk assessment, risk management, and aftereffect assessment. We hope to provide new ideas for the future research.

  20. Risk factors for breast cancer in the breast cancer risk model study of Guam and Saipan.

    Leon Guerrero, Rachael T; Novotny, Rachel; Wilkens, Lynne R; Chong, Marie; White, Kami K; Shvetsov, Yurii B; Buyum, Arielle; Badowski, Grazyna; Blas-Laguaña, Michelle

    2017-10-01

    Chamorro Pacific Islanders in the Mariana Islands have breast cancer incidence rates similar to, but mortality rates higher than, those of U.S. women. As breast cancer risk factors of women of the Mariana Islands may be unique because of ethnic and cultural differences, we studied established and suspected risk factors for breast cancer in this unstudied population. From 2010-2013, we conducted retrospective case-control study of female breast cancer (104 cases and 185 controls) among women in the Mariana Islands. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated for each of various lifestyle-related factors from logistic regression of breast cancer, in all women and in pre- and postmenopausal women separately. Tests for interaction of risk factors with ethnicity were based on the Wald statistics for cross-product terms. Of the medical and reproductive factors considered - age at menarche, breastfeeding, number of live births, age at first live birth, hormone use, and menopause - only age at first live birth was confirmed. Age at first live birth, among parous women, was higher among cases (mean 24.9 years) than controls (mean 23.2 years); with increased breast cancer risk (OR=2.53; 95% CI, 1.04-6.19 for age≥30y compared to risk and only in Filipino women. The association with many other established risk factors, such as BMI, hormone use and physical activity, were in the expected direction but were not significant. Associations for family history of breast cancer and alcohol intake were not evident CONCLUSIONS: The results provide a basis for cancer prevention guidance for women in the Mariana Islands. Copyright © 2017 The Author(s). Published by Elsevier Ltd.. All rights reserved.

  1. Acquired TGF beta 1 sensitivity and TGF beta 1 expression in cell lines established from a single small cell lung cancer patient during clinical progression

    Nørgaard, P; Damstrup, L; Rygaard, K

    1996-01-01

    Three small cell lung cancer cell lines established from a single patient during longitudinal follow-up were examined for in vitro expression of TGF beta and TGF beta receptors, i.e. the components of an autocrine loop. GLC 14 was established prior to treatment, GLC 16 on relapse after chemotherapy...... was found in GLC 16 and GLC 19. These cell lines were also growth inhibited by exogenously administrated TGF beta 1. TGF beta 1 mRNA and protein in its latent form was only expressed in the radiotherapy-resistant cell line, GLC 19. The results indicate that disease progression in this patient was paralleled...... II receptor gene, as examined by Southern blotting. Also, the type I receptor could not be detected by ligand binding assay in this cell line, despite expression of mRNA for this receptor. This agrees with previous findings that type I receptor cannot bind TGF beta 1 without co-expression of the type...

  2. “A rising tide lifts all boats”: establishing a multidisciplinary genomic tumor board for breast cancer patients with advanced disease

    Michelle L. McGowan

    2016-11-01

    Full Text Available Abstract Background Research suggests that multidisciplinary genomic tumor boards (MGTB can inform cancer patient care, though little is known about factors influencing how MGTBs interpret genomic test results, make recommendations, and perceive the utility of this approach. This study’s objective was to observe, describe, and assess the establishment of the Breast Multidisciplinary Genomic Tumor Board, the first MGTB focused on interpreting genomic test results for breast cancer patients with advanced disease. Methods We conducted a qualitative case study involving participant observation at monthly MGTB meetings from October 2013 through November 2014 and interviews with 12 MGTB members. We analyzed social dynamics and interactions within the MGTB regarding interpretation of genomic findings and participants’ views on effectiveness of the MGTB in using genomics to inform patient care. Results Twenty-two physicians, physician-scientists, basic scientists, bioethicists, and allied care professionals comprised the MGTB. The MGTB reviewed FoundationOne™ results for 40 metastatic breast cancer patients. Based on findings, the board mostly recommended referring patients to clinical trials (34 and medical genetics (15, and Food and Drug Administration-approved (FDA breast cancer therapies (13. Though multidisciplinary, recommendations were driven by medical oncologists. Interviewees described providing more precise care recommendations and professional development as advantages and the limited actionability of genomic test results as a challenge for the MGTB. Conclusions Findings suggest both feasibility and desirability of pooling professional expertise in genomically-guided breast cancer care and challenges to institutionalizing a Breast MGTB, specifically in promoting interdisciplinary contributions and managing limited actionability of genomic test results for patients with advanced disease.

  3. The Possibility Of Using The Business Model Canvas In The Establishment Of An Operator' S Business Plan

    Andrzej Tokarski

    2017-12-01

    The objective of the paper is to present both theoretical and practical possibilities of using the BMC in creating a business plan of an economic entity, which is a useful tool used especially by micro and small economic entities at the stage of establishing a business activity and a business model popular among product managers. The paper was written based on the literature of the subject of management and business plans creation.

  4. Analysis of risk factors and the establishment of a risk model for peripherally inserted central catheter thrombosis

    Fang Hu; Ruo-Nan Hao; Jie Zhang; Zhi-Cheng Ma

    2016-01-01

    Objective: To investigate the main risk factors of peripherally inserted central catheter (PICC) related upper extremity deep venous thrombosis and establish the risk predictive model of PICC-related upper extremity deep venous thrombosis. Methods: Patients with PICC who were hospitalized between January 2014 and July 2015 were studied retrospectively; they were divided into a thrombosis group (n = 52), with patients who had a venous thrombosis complication after PICC, and a no-thrombosis ...

  5. AOM/DSS Model of Colitis-Associated Cancer.

    Parang, Bobak; Barrett, Caitlyn W; Williams, Christopher S

    2016-01-01

    Our understanding of colitis-associated carcinoma (CAC) has benefited substantially from mouse models that faithfully recapitulate human CAC. Chemical models, in particular, have enabled fast and efficient analysis of genetic and environmental modulators of CAC without the added requirement of time-intensive genetic crossings. Here we describe the Azoxymethane (AOM)/Dextran Sodium Sulfate (DSS) mouse model of inflammatory colorectal cancer.

  6. Establishment of prostate cancer spheres from a prostate cancer cell line after phenethyl isothiocyanate treatment and discovery of androgen-dependent reversible differentiation between sphere and neuroendocrine cells.

    Chen, Yamei; Cang, Shundong; Han, Liying; Liu, Christina; Yang, Patrick; Solangi, Zeeshan; Lu, Quanyi; Liu, Delong; Chiao, J W

    2016-05-03

    Prostate cancer can transform from androgen-responsive to an androgen-independent phenotype. The mechanism responsible for the transformation remains unclear. We studied the effects of an epigenetic modulator, phenethyl isothiocyanate (PEITC), on the androgen-responsive LNCaP cells. After treatment with PEITC, floating spheres were formed with characteristics of prostate cancer stem cells (PCSC). These spheres were capable of self-renewal in media with and without androgen. They have been maintained in both types of media as long term cultures. Upon androgen deprivation, the adherent spheres differentiated to neuroendocrine cells (NEC) with decreased proliferation, expression of androgen receptor, and PSA. NEC reverse differentiated to spheres when androgen was replenished. The sphere cells expressed surface marker CD44 and had enhanced histone H3K4 acetylation, DNMT1 down-regulation and GSTP1 activation. We hypothesize that PEITC-mediated alteration in epigenomics of LNCaP cells may give rise to sphere cells, whereas reversible androgenomic alterations govern the shuttling between sphere PCSC and progeny NEC. Our findings identify unrecognized properties of prostate cancer sphere cells with multi-potential plasticity. This system will facilitate development of novel therapeutic agents and allow further exploration into epigenomics and androgenomics governing the transformation to hormone refractory prostate cancer.

  7. DSA-guided embolization in establishing different canine spinal cord ischemia models and relevant diffusion-weighted imaging study

    Zhang Jingsong; Sun Lijun; Huan Yi; He Hongde; Zhang Xuexin; Zhao Haitao; Zhang Jing; Zhang Xijing

    2006-01-01

    Objective: To evaluate DSA-guided embolization in establishing different spinal cord ischemia models of canine and relevant diffusion-weighted imaging (DWI) application. Methods: Nine canines were randomly divided into three groups with different matching of lipiodol and diatrizoate meglumine which were injected into bilateral intercostal arteries at 9-11 level guided by DSA monitor. Then observe the changes of motor function and pathologic findings, especially perform routine MRI and DWI by a 1.5 T MR system. Results: Except one case, 8 embolization models were established successfully. Among three groups, slight-group got slight injury and muscle power was about 3-5 grade and range of injury was about two vertebra distance; medium-group presented obvious paraplegia and muscle power was 0-1 grade and range of injury was between 3-4 vertebra distance; severe-group showed greater severity and larger range of injury. All lesions presented high signals at routine MRI and DWI. Conclusion: Using different matching of lipiodol and diatrizoate meglumine can establish different spinal cord ischemia models of canine by DSA- guided embolization and DWI can be performed successfully by 1.5 T MR system, which may be a good method for advanced study of spinal cord ischemia. (authors)

  8. Establishing an experimental rat model of photodynamically-induced retinal vein occlusion using erythrosin B

    Wei Chen

    2014-04-01

    Full Text Available AIM:To develop a reliable, reproducible rat model of retinal vein occlusion (RVO with a novel photosensitizer (erythrosin B and study the cellular responses in the retina.METHODS:Central and branch RVOs were created in adult male rats via photochemically-induced ischemia. Retinal changes were monitored via color fundus photography and fluorescein angiography at 1 and 3h, and 1, 4, 7, 14, and 21d after irradiation. Tissue slices were evaluated histopathologically. Retinal ganglion cell survival at different times after RVO induction was quantified by nuclear density count. Retinal thickness was also observed.RESULTS:For all rats in both the central and branch RVO groups, blood flow ceased immediately after laser irradiation and retinal edema was evident at one hour. The retinal detachment rate was 100% at 3h and developed into bullous retinal detachment within 24h. Retinal hemorrhages were not observed until 24h. Clearance of the occluded veins at 7d was observed by fluorescein angiography. Disease manifestation in the central RVO eyes was more severe than in the branch RVO group. A remarkable reduction in the ganglion cell count and retinal thickness was observed in the central RVO group by 21d, whereas moderate changes occurred in the branch RVO group.CONCLUSION: Rat RVO created by photochemically-induced ischemia using erythrosin B is a reproducible and reliable animal model for mimicking the key features of human RVO. However, considering the 100% rate of retinal detachment, this animal model is more suitable for studying RVO with chronic retinal detachment.

  9. The establishment of animal model of radiation-skin-burn and its changes of tissue metabolism

    Lu Xingan; Wu Shiliang; Wang Xiuzhen; Zhou Yinghui; Feng Yizhong; Tian Ye; Peng Miao

    2001-01-01

    The biochemistry metabolic changes of the tissues induced by 60 Co γ radiation or by accelerator β radiation on the animal local tissues were observed. The experiment results were shown as follows: (1) 60 Co γ radiation can induce the metabolic changes of the local tissue and led to ulcer or death. (2) Accelerator β radiation at the same dose of γ radiation can only produce ulcer but no death. (3) The biochemistry metabolic changes of the tissues induced by 60 Co γ radiation are similar to that by β radiation, but as a radiation-burn animal model, the latter is better

  10. USING THE SWOT MODEL IN ESTABLISHING THE STRATEGY AT AUTOMOBILE DACIA GROUPE RENAULT COMPANY

    Doruleţ GRĂDINARU

    2012-12-01

    Full Text Available SWOT analysis is a tool of the strategic management and it is used by the companies in the following situations: when they want to make ultimate decisions based on a complete analysis, in the strategic forecasting on three – five years, in the annual planning, when the company want a renewal or a radical change in its activity, or, each time when the company faces major difficulties which has to be solved as fast as possible. The SWOT model is also known as the Great strategy or the main strategy, being a part of the corporative strategies.

  11. Zebrafish a new sustainable vertebrate model established at DTU Food to study immunotoxicology

    Nielsen, Michael Engelbrecht; Schmidt, Jacob Günther

    2014-01-01

    to investigate the immune system and adverse immunotoxicological effects of chemical substances. At DTU Food we have just invested in a State-of-the-art zebrafish facility with fully automated control of water parameters. We are currently working with the influence of chemicals on the allograft reaction (tissue...... transplants from one individual to another of the same species) in skin, where e measure angiogenesis (formation of new blood vessels from pre-existing vessels) and expression of involved genes. The process of angiogenesis has proven to be a promising screening model, as angiogenesis can be followed by non...

  12. Assessing the Global Risk of Establishment of Cydia pomonella (Lepidoptera: Tortricidae) using CLIMEX and MaxEnt Niche Models.

    Kumar, Sunil; Neven, Lisa G; Zhu, Hongyu; Zhang, Runzhi

    2015-08-01

    Accurate assessment of insect pest establishment risk is needed by national plant protection organizations to negotiate international trade of horticultural commodities that can potentially carry the pests and result in inadvertent introductions in the importing countries. We used mechanistic and correlative niche models to quantify and map the global patterns of the potential for establishment of codling moth (Cydia pomonella L.), a major pest of apples, peaches, pears, and other pome and stone fruits, and a quarantine pest in countries where it currently does not occur. The mechanistic model CLIMEX was calibrated using species-specific physiological tolerance thresholds, whereas the correlative model MaxEnt used species occurrences and climatic spatial data. Projected potential distribution from both models conformed well to the current known distribution of codling moth. None of the models predicted suitable environmental conditions in countries located between 20°N and 20°S potentially because of shorter photoperiod, and lack of chilling requirement (Japan where codling moth currently does not occur but where its preferred host species (i.e., apple) is present. Average annual temperature and latitude were the main environmental variables associated with codling moth distribution at global level. The predictive models developed in this study present the global risk of establishment of codling moth, and can be used for monitoring potential introductions of codling moth in different countries and by policy makers and trade negotiators in making science-based decisions. © The Authors 2015. Published by Oxford University Press on behalf of Entomological Society of America. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  13. Lung cancer in never smokers Epidemiology and risk prediction models

    McCarthy, William J.; Meza, Rafael; Jeon, Jihyoun; Moolgavkar, Suresh

    2012-01-01

    In this chapter we review the epidemiology of lung cancer incidence and mortality among never smokers/ nonsmokers and describe the never smoker lung cancer risk models used by CISNET modelers. Our review focuses on those influences likely to have measurable population impact on never smoker risk, such as secondhand smoke, even though the individual-level impact may be small. Occupational exposures may also contribute importantly to the population attributable risk of lung cancer. We examine the following risk factors in this chapter: age, environmental tobacco smoke, cooking fumes, ionizing radiation including radon gas, inherited genetic susceptibility, selected occupational exposures, preexisting lung disease, and oncogenic viruses. We also compare the prevalence of never smokers between the three CISNET smoking scenarios and present the corresponding lung cancer mortality estimates among never smokers as predicted by a typical CISNET model. PMID:22882894

  14. Mathematical models in cell biology and cancer chemotherapy

    Eisen, Martin

    1979-01-01

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

  15. Establishment and application of the estimation model for pollutant concentrfation in agriculture drain

    Li, Qiangkun; Hu, Yawei; Jia, Qian; Song, Changji

    2018-02-01

    It is the key point of quantitative research on agricultural non-point source pollution load, the estimation of pollutant concentration in agricultural drain. In the guidance of uncertainty theory, the synthesis of fertilization and irrigation is used as an impulse input to the farmland, meanwhile, the pollutant concentration in agricultural drain is looked as the response process corresponding to the impulse input. The migration and transformation of pollutant in soil is expressed by Inverse Gaussian Probability Density Function. The law of pollutants migration and transformation in soil at crop different growth periods is reflected by adjusting parameters of Inverse Gaussian Distribution. Based on above, the estimation model for pollutant concentration in agricultural drain at field scale was constructed. Taking the of Qing Tong Xia Irrigation District in Ningxia as an example, the concentration of nitrate nitrogen and total phosphorus in agricultural drain was simulated by this model. The results show that the simulated results accorded with measured data approximately and Nash-Sutcliffe coefficients were 0.972 and 0.964, respectively.

  16. Establishment of a canine model of human type 2 diabetes mellitus by overexpressing phosphoenolypyruvate carboxykinase.

    Jeong, Yeon Woo; Lee, Geun-Shik; Kim, Joung Joo; Park, Sun Woo; Ko, Kyeong Hee; Kang, Mina; Kim, Yu Kyung; Jung, Eui-Man; Hyun, Sang Hwan; Shin, Taeyoung; Jeung, Eui-Bae; Hwang, Woo Suk

    2012-08-01

    Dogs are useful models for studying human metabolic diseases such as type 2 diabetes mellitus due to similarities in physiology, anatomy and life styles with humans. Somatic cell nuclear transfer (SCNT) facilitates the production of transgenic dogs. In this study, we generated transgenic dogs expressing the phosphoenolpyruvate carboxykinase (PEPCK) gene, which is closely involved in the pathogenesis of type 2 diabetes mellitus. In addition, we assessed the cloning efficiency associated with adult or fetal (cloned or natural mating) fibroblasts as a nuclear source. Cloning efficiency was determined by the fusion, pregnancy and cloning rates. The fusion rates were significantly high for fibroblasts from cloned fetuses, but the pregnancy and cloning rates were relatively high for cells from normal fetuses. Based on these data, fetal fibroblasts were selected as the nuclear donor for SCNT and genetically engineered to overexpress the PEPCK gene and dual selection marker genes controlled by the PEPCK promoter. The transgenic cells were introduced into oocytes and transferred into five recipient dogs, resulting in two pregnancies. Finally, three puppies were born and confirmed by microsatellite analysis to be genetically identical to the donor. One puppy successfully overexpressed PEPCK mRNA and protein in the liver. This canine disease model may be useful for studying the pathogenesis and/or therapeutic targets of type 2 diabetes mellitus.

  17. Establishing column batch repeatability according to Quality by Design (QbD) principles using modeling software.

    Rácz, Norbert; Kormány, Róbert; Fekete, Jenő; Molnár, Imre

    2015-04-10

    Column technology needs further improvement even today. To get information of batch-to-batch repeatability, intelligent modeling software was applied. Twelve columns from the same production process, but from different batches were compared in this work. In this paper, the retention parameters of these columns with real life sample solutes were studied. The following parameters were selected for measurements: gradient time, temperature and pH. Based on calculated results, batch-to-batch repeatability of BEH columns was evaluated. Two parallel measurements on two columns from the same batch were performed to obtain information about the quality of packing. Calculating the average of individual working points at the highest critical resolution (R(s,crit)) it was found that the robustness, calculated with a newly released robustness module, had a success rate >98% among the predicted 3(6) = 729 experiments for all 12 columns. With the help of retention modeling all substances could be separated independently from the batch and/or packing, using the same conditions, having high robustness of the experiments. Copyright © 2015 Elsevier B.V. All rights reserved.

  18. Which strategies reduce breast cancer mortality most? Collaborative modeling of optimal screening, treatment, and obesity prevention.

    Mandelblatt, Jeanne; van Ravesteyn, Nicolien; Schechter, Clyde; Chang, Yaojen; Huang, An-Tsun; Near, Aimee M; de Koning, Harry; Jemal, Ahmedin

    2013-07-15

    US breast cancer mortality is declining, but thousands of women still die each year. Two established simulation models examine 6 strategies that include increased screening and/or treatment or elimination of obesity versus continuation of current patterns. The models use common national data on incidence and obesity prevalence, competing causes of death, mammography characteristics, treatment effects, and survival/cure. Parameters are modified based on obesity (defined as BMI  ≥  30 kg/m(2) ). Outcomes are presented for the year 2025 among women aged 25+ and include numbers of cases, deaths, mammograms and false-positives; age-adjusted incidence and mortality; breast cancer mortality reduction and deaths averted; and probability of dying of breast cancer. If current patterns continue, the models project that there would be about 50,100-57,400 (range across models) annual breast cancer deaths in 2025. If 90% of women were screened annually from ages 40 to 54 and biennially from ages 55 to 99 (or death), then 5100-6100 fewer deaths would occur versus current patterns, but incidence, mammograms, and false-positives would increase. If all women received the indicated systemic treatment (with no screening change), then 11,400-14,500 more deaths would be averted versus current patterns, but increased toxicity could occur. If 100% received screening plus indicated therapy, there would be 18,100-20,400 fewer deaths. Eliminating obesity yields 3300-5700 fewer breast cancer deaths versus continuation of current obesity levels. Maximal reductions in breast cancer deaths could be achieved through optimizing treatment use, followed by increasing screening use and obesity prevention. © 2013 American Cancer Society.

  19. Application of artificial neural network model combined with four biomarkers in auxiliary diagnosis of lung cancer.

    Duan, Xiaoran; Yang, Yongli; Tan, Shanjuan; Wang, Sihua; Feng, Xiaolei; Cui, Liuxin; Feng, Feifei; Yu, Songcheng; Wang, Wei; Wu, Yongjun

    2017-08-01

    The purpose of the study was to explore the application of artificial neural network model in the auxiliary diagnosis of lung cancer and compare the effects of back-propagation (BP) neural network with Fisher discrimination model for lung cancer screening by the combined detections of four biomarkers of p16, RASSF1A and FHIT gene promoter methylation levels and the relative telomere length. Real-time quantitative methylation-specific PCR was used to detect the levels of three-gene promoter methylation, and real-time PCR method was applied to determine the relative telomere length. BP neural network and Fisher discrimination analysis were used to establish the discrimination diagnosis model. The levels of three-gene promoter methylation in patients with lung cancer were significantly higher than those of the normal controls. The values of Z(P) in two groups were 2.641 (0.008), 2.075 (0.038) and 3.044 (0.002), respectively. The relative telomere lengths of patients with lung cancer (0.93 ± 0.32) were significantly lower than those of the normal controls (1.16 ± 0.57), t = 4.072, P < 0.001. The areas under the ROC curve (AUC) and 95 % CI of prediction set from Fisher discrimination analysis and BP neural network were 0.670 (0.569-0.761) and 0.760 (0.664-0.840). The AUC of BP neural network was higher than that of Fisher discrimination analysis, and Z(P) was 0.76. Four biomarkers are associated with lung cancer. BP neural network model for the prediction of lung cancer is better than Fisher discrimination analysis, and it can provide an excellent and intelligent diagnosis tool for lung cancer.

  20. Establishing the existence of a distance-based upper bound for a fuzzy DEA model using duality

    Soleimani-damaneh, M.

    2009-01-01

    In a recent paper [Soleimani-damaneh M. Fuzzy upper bounds and their applications. Chaos, Solitons and Fractals 2008;36:217-25.], I established the existence of a distance-based fuzzy upper bound for the objective function of a fuzzy DEA model, using the properties of a discussed signed distance, and provided an effective approach to solve that model. In this paper a new dual-based proof for the existence of the above-mentioned upper bound is provided which gives a useful insight into the theory of fuzzy DEA.

  1. Establishment of a Zebrafish Infection Model for the Study of Wild-Type and Recombinant European Sheatfish Virus.

    Martín, Verónica; Mavian, Carla; López Bueno, Alberto; de Molina, Antonio; Díaz, Eduardo; Andrés, Germán; Alcami, Antonio; Alejo, Alí

    2015-10-01

    Amphibian-like ranaviruses include pathogens of fish, amphibians, and reptiles that have recently evolved from a fish-infecting ancestor. The molecular determinants of host range and virulence in this group are largely unknown, and currently fish infection models are lacking. We show that European sheatfish virus (ESV) can productively infect zebrafish, causing a lethal pathology, and describe a method for the generation of recombinant ESV, establishing a useful model for the study of fish ranavirus infections. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

  2. Korean risk assessment model for breast cancer risk prediction.

    Park, Boyoung; Ma, Seung Hyun; Shin, Aesun; Chang, Myung-Chul; Choi, Ji-Yeob; Kim, Sungwan; Han, Wonshik; Noh, Dong-Young; Ahn, Sei-Hyun; Kang, Daehee; Yoo, Keun-Young; Park, Sue K

    2013-01-01

    We evaluated the performance of the Gail model for a Korean population and developed a Korean breast cancer risk assessment tool (KoBCRAT) based upon equations developed for the Gail model for predicting breast cancer risk. Using 3,789 sets of cases and controls, risk factors for breast cancer among Koreans were identified. Individual probabilities were projected using Gail's equations and Korean hazard data. We compared the 5-year and lifetime risk produced using the modified Gail model which applied Korean incidence and mortality data and the parameter estimators from the original Gail model with those produced using the KoBCRAT. We validated the KoBCRAT based on the expected/observed breast cancer incidence and area under the curve (AUC) using two Korean cohorts: the Korean Multicenter Cancer Cohort (KMCC) and National Cancer Center (NCC) cohort. The major risk factors under the age of 50 were family history, age at menarche, age at first full-term pregnancy, menopausal status, breastfeeding duration, oral contraceptive usage, and exercise, while those at and over the age of 50 were family history, age at menarche, age at menopause, pregnancy experience, body mass index, oral contraceptive usage, and exercise. The modified Gail model produced lower 5-year risk for the cases than for the controls (p = 0.017), while the KoBCRAT produced higher 5-year and lifetime risk for the cases than for the controls (pKorean women, especially urban women.

  3. Establishment of Early Endpoints in Mouse Total-Body Irradiation Model.

    Amory Koch

    Full Text Available Acute radiation sickness (ARS following exposure to ionizing irradiation is characterized by radiation-induced multiorgan dysfunction/failure that refers to progressive dysfunction of two or more organ systems, the etiological agent being radiation damage to cells and tissues over time. Radiation sensitivity data on humans and animals has made it possible to describe the signs associated with ARS. A mouse model of total-body irradiation (TBI has previously been developed that represents the likely scenario of exposure in the human population. Herein, we present the Mouse Intervention Scoring System (MISS developed at the Veterinary Sciences Department (VSD of the Armed Forces Radiobiology Research Institute (AFRRI to identify moribund mice and decrease the numbers of mice found dead, which is therefore a more humane refinement to death as the endpoint. Survival rates were compared to changes in body weights and temperatures in the mouse (CD2F1 male TBI model (6-14 Gy, 60Co γ-rays at 0.6 Gy min-1, which informed improvements to the Scoring System. Individual tracking of animals via implanted microchips allowed for assessment of criteria based on individuals rather than by group averages. From a total of 132 mice (92 irradiated, 51 mice were euthanized versus only four mice that were found dead (7% of non-survivors. In this case, all four mice were found dead after overnight periods between observations. Weight loss alone was indicative of imminent succumbing to radiation injury, however mice did not always become moribund within 24 hours while having weight loss >30%. Only one survivor had a weight loss of greater than 30%. Temperature significantly dropped only 2-4 days before death/euthanasia in 10 and 14 Gy animals. The score system demonstrates a significant refinement as compared to using subjective assessment of morbidity or death as the endpoint for these survival studies.

  4. Design ensemble machine learning model for breast cancer diagnosis.

    Hsieh, Sheau-Ling; Hsieh, Sung-Huai; Cheng, Po-Hsun; Chen, Chi-Huang; Hsu, Kai-Ping; Lee, I-Shun; Wang, Zhenyu; Lai, Feipei

    2012-10-01

    In this paper, we classify the breast cancer of medical diagnostic data. Information gain has been adapted for feature selections. Neural fuzzy (NF), k-nearest neighbor (KNN), quadratic classifier (QC), each single model scheme as well as their associated, ensemble ones have been developed for classifications. In addition, a combined ensemble model with these three schemes has been constructed for further validations. The experimental results indicate that the ensemble learning performs better than individual single ones. Moreover, the combined ensemble model illustrates the highest accuracy of classifications for the breast cancer among all models.

  5. Hpm of Estrogen Model on the Dynamics of Breast Cancer

    Govindarajan, A.; Balamuralitharan, S.; Sundaresan, T.

    2018-04-01

    We enhance a deterministic mathematical model involving universal dynamics on breast cancer with immune response. This is population model so includes Normal cells class, Tumor cells, Immune cells and Estrogen. The eects regarding Estrogen are below incorporated in the model. The effects show to that amount the arrival of greater Estrogen increases the danger over growing breast cancer. Furthermore, approximate solution regarding nonlinear differential equations is arrived by Homotopy Perturbation Method (HPM). Hes HPM is good and correct technique after solve nonlinear differential equation directly. Approximate solution learnt with the support of that method is suitable same as like the actual results in accordance with this models.

  6. Renewable Energy Cost Modeling: A Toolkit for Establishing Cost-Based Incentives in the United States; March 2010 -- March 2011

    Gifford, J. S.; Grace, R. C.; Rickerson, W. H.

    2011-05-01

    This report is intended to serve as a resource for policymakers who wish to learn more about establishing cost-based incentives. The report will identify key renewable energy cost modeling options, highlight the policy implications of choosing one approach over the other, and present recommendations on the optimal characteristics of a model to calculate rates for cost-based incentives, feed-in tariffs (FITs), or similar policies. These recommendations will be utilized in designing the Cost of Renewable Energy Spreadsheet Tool (CREST). Three CREST models will be publicly available and capable of analyzing the cost of energy associated with solar, wind, and geothermal electricity generators. The CREST models will be developed for use by state policymakers, regulators, utilities, developers, and other stakeholders to assist them in current and future rate-setting processes for both FIT and other renewable energy incentive payment structures and policy analyses.

  7. Establishing Approaches to Modeling the Ares I-X and Ares I Roll Control System with Free-stream Interaction

    Pao, S. Paul; Deere, Karen A.; Abdol-Hamid, Khales S.

    2011-01-01

    Approaches were established for modeling the roll control system and analyzing the jet interactions of the activated roll control system on Ares-type configurations using the USM3D Navier-Stokes solver. Components of the modeling approach for the roll control system include a choice of turbulence models, basis for computing a dynamic equivalence of the real gas rocket exhaust flow in terms of an ideal gas, and techniques to evaluate roll control system performance for wind tunnel and flight conditions. A simplified Ares I-X configuration was used during the development phase of the roll control system modeling approach. A limited set of Navier-Stokes solutions was obtained for the purposes of this investigation and highlights of the results are included in this paper. The USM3D solutions were compared to equivalent solutions at select flow conditions from a real gas Navier- Stokes solver (Loci-CHEM) and a structured overset grid Navier-Stokes solver (OVERFLOW).

  8. [A novel chemo-resistant gene MSX2 discovered by establishment of two pancreatic cancer drug resistant cell lines JF305/CDDP and PANC-1/GEM].

    Yuan, W; Sui, C G; Ma, X; Ma, J

    2018-05-23

    Objective: To explore new multidrug resistant genes of pancreatic cancer by establishment and characterization of chemo-resistant cell lines. Methods: The cisplatin-resistant cell line JF305/CDDP and the gemcitabine-resistant cell line PANC-1/GEM were induced by high-dose intermittent treatment. CCK-8 assay was used to detect the 50% inhibiting concentration (IC(50)), drug resistance index (R), cross-resistance, and growth difference of different cells. The changes of cell cycle and migration ability of drug-resistant cells were determined by flow cytometry and transwell assay, respectively. And then real-time fluorescence quantitative PCR was used to detect the expression of multidrug resistance-related genes. Results: The drug resistance indexes of JF305/CDDP and PANC-1/GEM were 15.3 and 27.31, respectively, and there was cross-resistance. Compared with the parental cells, the proliferation rate of JF305/CDDP was decreased by 40% on the fourth day ( P PANC-1 cells upregulated MRP2 level ( P PANC-1/GEM, were successfully established. MSX2 might be a new drug resistance related gene in pancreatic cancer cells by up-regulation of MRP2 expression.

  9. Establishment and characterization of new cell lines of anaplastic pancreatic cancer, which is a rare malignancy: OCUP-A1 and OCUP-A2

    Miura, Kotaro; Kimura, Kenjiro; Amano, Ryosuke; Yamazoe, Sadaaki; Ohira, Go; Murata, Akihiro; Nishio, Kohei; Hasegawa, Tsuyoshi; Yashiro, Masakazu; Nakata, Bunzo; Ohira, Masaichi; Hirakawa, Kosei

    2016-01-01

    Anaplastic pancreatic cancer (APC) cell lines have been scarcely established. The morphology, gene expressions, karyotyping and epithelial-mesenchymal transition markers of newly established APC cell lines OCUP-A1 and OCUP-A2 were analyzed. Their abilities of proliferation under normoxia and hypoxia, migration and invasion were compared to 4 commercially available pancreatic ductal adenocarcinoma (PDA) cell lines. Their induction of angiogenesis, stem-like cell population and subcutaneous tumor growth in nude mice were estimated, comparing 2 PDA cell lines examined here. OCUP-A1 and OCUP-A2 cells continuously grew with spindle and polygonal shapes, respectively. Gene analysis revealed 9 gene mutations including KRAS and TP53. Karyotyping clarified numerical structural abnormalities in both cells. Loss of E-cadherin and expression of vimentin in both cell lines were observed. The doubling time of both cell lines was approximately 20 h. Proliferation, migration and invasion abilities were not notable compared to other PDA cell lines. However stem-like cell population of both cell lines was superior to a part of PDA cell lines. Moreover OCUP-A1 showed stronger hypoxia tolerance and induction of angiogenesis than other PDA cell lines. The tumorigenicity in vivo of OCUP-A2 was stronger than conventional PDA cell lines. The OCUP-A1 and OCUP-A2 cell lines of rare malignancies might be useful for investigating the biology of pancreatic cancer

  10. Identification of luminal breast cancers that establish a tumor-supportive macroenvironment defined by proangiogenic platelets and bone marrow-derived cells.

    Kuznetsov, Hanna S; Marsh, Timothy; Markens, Beth A; Castaño, Zafira; Greene-Colozzi, April; Hay, Samantha A; Brown, Victoria E; Richardson, Andrea L; Signoretti, Sabina; Battinelli, Elisabeth M; McAllister, Sandra S

    2012-12-01

    Breast cancer recurrence rates vary following treatment, suggesting that tumor cells disseminate early from primary sites but remain indolent indefinitely before progressing to symptomatic disease. The reasons why some indolent disseminated tumors erupt into overt disease are unknown. We discovered a novel process by which certain luminal breast cancer (LBC) cells and patient tumor specimens (LBC "instigators") establish a systemic macroenvironment that supports outgrowth of otherwise-indolent disseminated tumors ("responders"). Instigating LBCs secrete cytokines that are absorbed by platelets, which are recruited to responding tumor sites where they aid vessel formation. Instigator-activated bone marrow cells enrich responding tumor cell expression of CD24, an adhesion molecule for platelets, and provide a source of VEGF receptor 2(+) tumor vessel cells. This cascade results in growth of responder adenocarcinomas and is abolished when platelet activation is inhibited by aspirin. These findings highlight the macroenvironment as an important component of disease progression that can be exploited therapeutically. Currently, processes that mediate progression of otherwise indolent tumors are not well understood, making it difficult to accurately predict which cancer patients are likely to relapse. Our findings highlight the macroenvironment as an important component of disease progression that can be exploited to more accurately identify patients who would benefit from adjuvant therapy. ©2012 AACR.

  11. Combined Treatment Effects of Radiation and Immunotherapy: Studies in an Autochthonous Prostate Cancer Model

    Wada, Satoshi; Harris, Timothy J.; Tryggestad, Erik; Yoshimura, Kiyoshi; Zeng, Jing; Yen, Hung-Rong; Getnet, Derese; Grosso, Joseph F.; Bruno, Tullia C.; De Marzo, Angelo M.

    2013-01-01

    Purpose: To optimize the combination of ionizing radiation and cellular immunotherapy using a preclinical autochthonous model of prostate cancer. Methods and Materials: Transgenic mice expressing a model antigen under a prostate-specific promoter were treated using a platform that integrates cone-beam CT imaging with 3-dimensional conformal therapy. Using this technology we investigated the immunologic and therapeutic effects of combining ionizing radiation with granulocyte/macrophage colony-stimulating factor-secreting cellular immunotherapy for prostate cancer in mice bearing autochthonous prostate tumors. Results: The combination of ionizing radiation and immunotherapy resulted in a significant decrease in pathologic tumor grade and gross tumor bulk that was not evident with either single-modality therapy. Furthermore, combinatorial therapy resulted in improved overall survival in a preventive metastasis model and in the setting of established micrometastases. Mechanistically, combined therapy resulted in an increase of the ratio of effector-to-regulatory T cells for both CD4 and CD8 tumor-infiltrating lymphocytes. Conclusions: Our preclinical model establishes a potential role for the use of combined radiation-immunotherapy in locally advanced prostate cancer, which warrants further exploration in a clinical setting

  12. Combined Treatment Effects of Radiation and Immunotherapy: Studies in an Autochthonous Prostate Cancer Model

    Wada, Satoshi [Department of Oncology, James Buchanan Brady Urological Institute, Johns Hopkins Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, Maryland (United States); Harris, Timothy J.; Tryggestad, Erik [Department of Radiation Oncology and Molecular Radiation Sciences, James Buchanan Brady Urological Institute, Johns Hopkins Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, Maryland (United States); Yoshimura, Kiyoshi [Department of Oncology, James Buchanan Brady Urological Institute, Johns Hopkins Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, Maryland (United States); Zeng, Jing [Department of Radiation Oncology and Molecular Radiation Sciences, James Buchanan Brady Urological Institute, Johns Hopkins Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, Maryland (United States); Yen, Hung-Rong; Getnet, Derese; Grosso, Joseph F.; Bruno, Tullia C. [Department of Oncology, James Buchanan Brady Urological Institute, Johns Hopkins Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, Maryland (United States); De Marzo, Angelo M. [Department of Pathology, James Buchanan Brady Urological Institute, Johns Hopkins Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, Maryland (United States); Department of Urology, James Buchanan Brady Urological Institute, Johns Hopkins Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, Maryland (United States); and others

    2013-11-15

    Purpose: To optimize the combination of ionizing radiation and cellular immunotherapy using a preclinical autochthonous model of prostate cancer. Methods and Materials: Transgenic mice expressing a model antigen under a prostate-specific promoter were treated using a platform that integrates cone-beam CT imaging with 3-dimensional conformal therapy. Using this technology we investigated the immunologic and therapeutic effects of combining ionizing radiation with granulocyte/macrophage colony-stimulating factor-secreting cellular immunotherapy for prostate cancer in mice bearing autochthonous prostate tumors. Results: The combination of ionizing radiation and immunotherapy resulted in a significant decrease in pathologic tumor grade and gross tumor bulk that was not evident with either single-modality therapy. Furthermore, combinatorial therapy resulted in improved overall survival in a preventive metastasis model and in the setting of established micrometastases. Mechanistically, combined therapy resulted in an increase of the ratio of effector-to-regulatory T cells for both CD4 and CD8 tumor-infiltrating lymphocytes. Conclusions: Our preclinical model establishes a potential role for the use of combined radiation-immunotherapy in locally advanced prostate cancer, which warrants further exploration in a clinical setting.

  13. Establishment and application of performance evaluation model for collection and transportation system of municipal solid waste

    彭绪亚; 林晓东; 贾传兴; 王渝昆; 黄媛媛

    2009-01-01

    On the basis of analyzing the typical waste collection and transportation mode,the evaluation index system for performance of the waste collection and transportation system was proposed with three grades,which related to six factors,such as economic evaluation,high efficient evaluation,environmental impact assessment,resource evaluation,evaluation of security and emergency,evaluation of management and society. With the performance evaluation theory,the performance evaluation model of waste collection and transportation system was constructed,which quantified the grading standard of index and determined the index weight in analytic hierarchy process (AHP). After evaluating the waste collection and transportation system of the main districts of Chongqing city,the results show that the it has an excellent performance evaluation grade with very high performance level of three indices involving evaluation of management and society,environmental impact assessment,evaluation of security and emergency and quite low performance level of two indices that include high efficient evaluation and economic evaluation.

  14. Establishing verbal repertoires in children with autism using function-based video modeling.

    Plavnick, Joshua B; Ferreri, Summer J

    2011-01-01

    Previous research suggests that language-training procedures for children with autism might be enhanced following an assessment of conditions that evoke emerging verbal behavior. The present investigation examined a methodology to teach recognizable mands based on environmental variables known to evoke participants' idiosyncratic communicative responses in the natural environment. An alternating treatments design was used during Experiment 1 to identify the variables that were functionally related to gestures emitted by 4 children with autism. Results showed that gestures functioned as requests for attention for 1 participant and as requests for assistance to obtain a preferred item or event for 3 participants. Video modeling was used during Experiment 2 to compare mand acquisition when video sequences were either related or unrelated to the results of the functional analysis. An alternating treatments within multiple probe design showed that participants repeatedly acquired mands during the function-based condition but not during the nonfunction-based condition. In addition, generalization of the response was observed during the former but not the latter condition.

  15. [Establishment and practice of traditional Chinese medicine property cognitive model based on three elements].

    Zhang, Bing; Jin, Rui; Huang, Jianmei; Liu, Xiaoqing; Xue, Chunmiao; Lin, Zhijian

    2012-08-01

    Traditional Chinese medicine (TCM) property theory is believed to be a key and difficult point of basic theory studies of TCM. Complex concepts, components and characteristics of TCM property have long puzzled researchers and urged them to develop new angles and approaches. In the view of cognitive science, TCM property theory is a cognitive process of storing, extracting, rebuilding and summarizing the sensory information about TCMs and their effects during the medical practice struggling against diseases under the guidance of traditional Chinese philosophical thinking. The cognitive process of TCM property has particular cognitive elements and strategies. Taking into account clinical application characteristics of TCMs, this study defines the particular cognitive elements. In the combination of research methods of modern chemistry, biology and mathematics, and on the basis early-stage work for five years, we have built a TCM property cognition model based on three elements and practiced with drugs with pungent and hot properties as example, in the hope of interpreting TCM properties with modern science and providing thoughts for the nature of medical properties and instruction for rational clinical prescription.

  16. Establishment of a mouse model for the complete mosquito-mediated transmission cycle of Zika virus.

    Yi-Ping Kuo

    2018-04-01

    Full Text Available Zika virus (ZIKV is primarily transmitted by Aedes mosquitoes in the subgenus Stegomyia but can also be transmitted sexually and vertically in humans. STAT1 is an important downstream factor that mediates type I and II interferon signaling. In the current study, we showed that mice with STAT1 knockout (Stat1-/- were highly susceptible to ZIKV infection. As low as 5 plaque-forming units of ZIKV could cause viremia and death in Stat1-/- mice. ZIKV replication was initially detected in the spleen but subsequently spread to the brain with concomitant reduction of the virus in the spleen in the infected mice. Furthermore, ZIKV could be transmitted from mosquitoes to Stat1-/- mice back to mosquitoes and then to naïve Stat1-/- mice. The 50% mosquito infectious dose of viremic Stat1-/- mouse blood was close to 810 focus-forming units (ffu/ml. Our further studies indicated that the activation of macrophages and conventional dendritic cells were likely critical for the resolution of ZIKV infection. The newly developed mouse and mosquito transmission models for ZIKV infection will be useful for the evaluation of antiviral drugs targeting the virus, vector, and host.

  17. Using a data-constrained model of home range establishment to predict abundance in spatially heterogeneous habitats.

    Mark C Vanderwel

    Full Text Available Mechanistic modelling approaches that explicitly translate from individual-scale resource selection to the distribution and abundance of a larger population may be better suited to predicting responses to spatially heterogeneous habitat alteration than commonly-used regression models. We developed an individual-based model of home range establishment that, given a mapped distribution of local habitat values, estimates species abundance by simulating the number and position of viable home ranges that can be maintained across a spatially heterogeneous area. We estimated parameters for this model from data on red-backed vole (Myodes gapperi abundances in 31 boreal forest sites in Ontario, Canada. The home range model had considerably more support from these data than both non-spatial regression models based on the same original habitat variables and a mean-abundance null model. It had nearly equivalent support to a non-spatial regression model that, like the home range model, scaled an aggregate measure of habitat value from local associations with habitat resources. The home range and habitat-value regression models gave similar predictions for vole abundance under simulations of light- and moderate-intensity partial forest harvesting, but the home range model predicted lower abundances than the regression model under high-intensity disturbance. Empirical regression-based approaches for predicting species abundance may overlook processes that affect habitat use by individuals, and often extrapolate poorly to novel habitat conditions. Mechanistic home range models that can be parameterized against abundance data from different habitats permit appropriate scaling from individual- to population-level habitat relationships, and can potentially provide better insights into responses to disturbance.

  18. CysLT(1)R antagonists inhibit tumor growth in a xenograft model of colon cancer.

    Savari, Sayeh; Liu, Minghui; Zhang, Yuan; Sime, Wondossen; Sjölander, Anita

    2013-01-01

    The expression of the inflammatory G-protein coupled receptor CysLT1R has been shown to be upregulated in colon cancer patients and associated with poor prognosis. The present study investigated the correlation between CysLT1R and colon cancer development in vivo using CysLT1R antagonists (ZM198,615 or Montelukast) and the nude mouse xenograft model. Two drug administration regimens were established. The first regimen was established to investigate the importance of CysLT1R in tumor initiation. Nude mice were inoculated with 50 µM CysLT1R antagonist-pretreated HCT-116 colon cancer cells and received continued treatment (5 mg/kg/day, intraperitoneally). The second regimen aimed to address the role of CysLT1R in tumor progression. Nude mice were inoculated with non-pretreated HCT-116 cells and did not receive CysLT1R antagonist treatment until recordable tumor appearance. Both regimens resulted in significantly reduced tumor size, attributed to changes in proliferation and apoptosis as determined by reduced Ki-67 levels and increased levels of p21(WAF/Cip1) (Pcolon cancer cell line HCT-116 and CysLT1R antagonists. In addition to significant reductions in cell proliferation, adhesion and colony formation, we observed induction of cell cycle arrest and apoptosis in a dose-dependent manner. The ability of Montelukast to inhibit growth of human colon cancer xenograft was further validated by using two additional colon cancer cell lines, SW-480 and HT-29. Our results demonstrate that CysLT1R antagonists inhibit growth of colon cancer xenografts primarily by reducing proliferation and inducing apoptosis of the tumor cells.

  19. The KCa3.1 blocker TRAM34 reverses renal damage in a mouse model of established diabetic nephropathy.

    Chunling Huang

    Full Text Available Despite optimal control of hyperglycaemia, hypertension, and dyslipidaemia, the number of patients with diabetic nephropathy (DN continues to grow. Strategies to target various signaling pathways to prevent DN have been intensively investigated in animal models and many have been proved to be promising. However, targeting these pathways once kidney disease is established, remain unsatisfactory. The clinical scenario is that patients with diabetes mellitus often present with established kidney damage and need effective treatments to repair and reverse the kidney damage. In this studies, eNOS-/- mice were administered with streptozotocin to induce diabetes. At 24 weeks, at which time we have previously demonstrated albuminuria and pathological changes of diabetic nephropathy, mice were randomised to receive TRAM34 subcutaneously, a highly selective inhibitor of potassium channel KCa3.1 or DMSO (vehicle for a further 14 weeks. Albuminuria was assessed, inflammatory markers (CD68, F4/80 and extracellular matrix deposition (type I collagen and fibronectin in the kidneys were examined. The results clearly demonstrate that TRAM34 reduced albuminuria, decreased inflammatory markers and reversed extracellular matrix deposition in kidneys via inhibition of the TGF-β1 signaling pathway. These results indicate that KCa3.1 blockade effectively reverses established diabetic nephropathy in this rodent model and provides a basis for progressing to human studies.

  20. Establishing a Near Term Lunar Farside Gravity Model via Inexpensive Add-on Navigation Payload

    Folta, David; Mesarch, Michael; Miller, Ronald; Bell, David; Jedrey, Tom; Butman, Stanley; Asmar, Sami

    2007-01-01

    The Space Communications and Navigation, Constellation Integration Project (SCIP) is tasked with defining, developing, deploying and operating an evolving multi-decade communications and navigation (C/N) infrastructure including services and subsystems that will support both robotic and human exploration activities at the Moon. This paper discusses an early far side gravitational mapping service and related telecom subsystem that uses an existing spacecraft (WIND) and the Lunar Reconnaissance Orbiter (LRO) to collect data that would address several needs of the SCIP. An important aspect of such an endeavor is to vastly improve the current lunar gravity model while demonstrating the navigation and stationkeeping of a relay spacecraft. We describe a gravity data acquisition activity and the trajectory design of the relay orbit in an Earth-Moon L2 co-linear libration orbit. Several phases of the transfer from an Earth-Sun to the Earth-Moon region are discussed along with transfers within the Earth-Moon system. We describe a proposed, but not integrated, add-on to LRO scheduled to be launched in October of 2008. LRO provided a real host spacecraft against which we designed the science payload and mission activities. From a strategic standpoint, LRO was a very exciting first flight opportunity for gravity science data collection. Gravity Science data collection requires the use of one or more low altitude lunar polar orbiters. Variations in the lunar gravity field will cause measurable variations in the orbit of a low altitude lunar orbiter. The primary means to capture these induced motions is to monitor the Doppler shift of a radio signal to or from the low altitude spacecraft, given that the signal is referenced to a stable frequency reference. For the lunar far side, a secondary orbiting radio signal platform is required. We provide an in-depth look at link margins, trajectory design, and hardware implications. Our approach posed minimum risk to a host mission while

  1. A study of Ground Source Heat Pump based on a heat infiltrates coupling model established with FEFLOW

    Chen, H.; Hu, C.; Chen, G.; Zhang, Q.

    2017-12-01

    Geothermal heat is a viable source of energy and its environmental impact in terms of CO2 emissions is significantly lower than conventional fossil fuels. it is vital that engineers acquire a proper understanding about the Ground Source Heat Pump (GSHP). In this study, the model of the borehole exchanger under conduction manners and heat infiltrates coupling manners was established with FEFLOW. The energy efficiency, heat transfer endurance and heat transfer in the unit depth were introduced to quantify the energy efficient and the endurance period. The performance of a the Borehole Exchanger (BHE) in soil with and without groundwater seepage was analyzed of heat transfer process between the soil and the working fluid. Basing on the model, the varied regularity of energy efficiency performance an heat transfer endurance with the conditions including the different configuration of the BHE, the soil properties, thermal load characteristic were discussed. Focus on the heat transfer process in multi-layer soil which one layer exist groundwater flow. And an investigation about thermal dispersivity was also analyzed its influence on heat transfer performance. The final result proves that the model of heat infiltrates coupling model established in this context is reasonable, which can be applied to engineering design.

  2. Molecular genetics of cancer and tumorigenesis: Drosophila models

    Wu-Min Deng

    2011-01-01

    Why do some cells not respond to normal control of cell division and become tumorous? Which signals trigger some tumor cells to migrate and colonize other tissues? What genetic factors are responsible for tumorigenesis and cancer development? What environmental factors play a role in cancer formation and progression? In how many ways can our bodies prevent and restrict the growth of cancerous cells?How can we identify and deliver effective drugs to fight cancer? In the fight against cancer,which kills more people than any other disease,these and other questions have long interested researchers from a diverse range of fields.To answer these questions and to fight cancer more effectively,we must increase our understanding of basic cancer biology.Model organisms,including the fruit fly Drosophila melanogaster,have played instrumental roles in our understanding of this devastating disease and the search for effective cures.Drosophila and its highly effective,easy-touse,and ever-expanding genetic tools have contributed toand enriched our knowledge of cancer and tumor formation tremendously.

  3. Transgenic Rat Models for Breast Cancer Research

    1996-10-01

    colleagues, Dr. Henry Pitot , an expert in hepatocarcinogenesis, and Dr. Michael Gould, an expert in breast cancer. Through our initial attempts at...974-978. 29. Dragan, Y.P. and H.C. Pitot . 1992. The role of the stages of initiation and promotion in phenotypic diversity during hepatocarcinogenesis

  4. A model for establishing a win-win relationship between a wood pellets manufacturer and its customers

    Uran, Vedran

    2010-01-01

    This paper investigates the possibility of establishing a win-win relationship between a wood pellets manufacturer and its customers when the manufacturer possesses a power plant fueled by biomass and buys wood material from forest companies. Two prerequisites must be fulfilled for this relationship. First, the price of wood pellets should be lower than the fuel currently used by potential wood pellets customers and, second, the price of wood material as a raw material for producing the wood pellets should not jeopardize the profitability of the operations of the wood pellets manufacturer, who also produces electricity from biomass and sells it to the state at the feed-in tariff price. A mathematical model has been developed for each prerequisite and applied to several examples. The results demonstrate that a win-win relation can be established in Croatia and most of the Member States of the EU. (author)

  5. Comparison of the multi-drug resistant human hepatocellular carcinoma cell line Bel-7402/ADM model established by three methods

    Zhong Xingguo

    2010-08-01

    Full Text Available Abstract Background To compare the biological characteristics of three types of human hepatocellular carcinoma multi-drug resistant cell sub-lines Bel-7402/ADM models established by three methods. Methods Established human hepatocellular carcinoma adriamycin (ADM multi-drug resistant cell sub-lines models Bel-7402/ADMV, Bel-7402/ADML and Bel-7402/ADMS by three methods of in vitro concentration gradient increased induction, nude mice liver-implanted induction and subcutaneous-implanted induction respectively. Phase contrast microscopy was used to observe the cells and the MTT (methyl thiazolyl tetrazolium method was used to detect drug resistance of the three different sub-lines of cells. Results The three groups of drug resistant cells, Bel-7402/ADMV, Bel-7402/ADML and Bel-7402/ADMS generated cross-resistance to ADM and CDDP (cis-Diaminedichloroplatinum, but showed a significant difference in resistance to Bel-7402 IC50 value (P V, 46 h (Bel-7402/ADML, and 45 h (Bel-7402/ADMS. The excretion rates of ADM were significantly increased compared with the parent cell (34.14% line and were 81.06% (Bel-7402/ADMV, 66.56% (Bel-7402/ADML and 61.56% (Bel-7402/ADMS. Expression of P-gp and MRP in the three groups of resistant cells was significantly enhanced (P P > 0.05. Conclusions Stable resistance was involved in the resistant cell line model established by the above three methods. Liver implantation was a good simulation of human hepatocellular and proved to be an ideal model with characteristics similar to human hepatocellular biology and the pharmacokinetics of anticancer drugs.

  6. Establishment and Evaluation of a Rat Model of Sidestream Cigarette Smoke-Induced Chronic Obstructive Pulmonary Disease

    Genfa Wang

    2018-02-01

    Full Text Available Chronic obstructive pulmonary disease (COPD is a common cause of mortality worldwide. The current lack of an animal model that can be established within a certain time frame and imitate the unique features of the disease is a major limiting factor in its study. The present study established and evaluated an animal model of COPD that represents the early and advanced stage features using short-, middle-, and long-term sidestream cigarette smoke (CS exposure. One hundred and nine Sprague–Dawley rats were randomly divided into 10 groups for different periods of sidestream CS exposure or no exposure (i.e., normal groups. The rats were exposed to CS from 3R4F cigarettes in an exposure chamber. Histological analysis was performed to determine pathological changes. We also conducted open-field tests, lung function evaluations, and cytokine analysis of the blood serum, bronchoalveolar lavage fluid, and lung tissue. The lung tissue protein levels, blood gases, and were also analyzed. As the CS exposure time increased, the indicators associated with oxidative stress, inflammatory responses, and airway remodeling were greater in the CS exposure groups than in the normal group. At 24 and 36 weeks, the COPD model rats displayed the middle- and advanced-stage features of COPD, respectively. In the 8-week CS exposure group, after the CS exposure was stopped for 4 weeks, inflammatory responses and oxidative responses were ameliorated and lung function exacerbation was reduced compared with the 12-week CS exposure group. Therefore, we established a more adequate rat model of sidestream CS induced COPD, which will have great significance for a better understanding of the pathogenesis of COPD and drug effectiveness evaluation.

  7. Model Comparison for Breast Cancer Prognosis Based on Clinical Data.

    Sabri Boughorbel

    Full Text Available We compared the performance of several prediction techniques for breast cancer prognosis, based on AU-ROC performance (Area Under ROC for different prognosis periods. The analyzed dataset contained 1,981 patients and from an initial 25 variables, the 11 most common clinical predictors were retained. We compared eight models from a wide spectrum of predictive models, namely; Generalized Linear Model (GLM, GLM-Net, Partial Least Square (PLS, Support Vector Machines (SVM, Random Forests (RF, Neural Networks, k-Nearest Neighbors (k-NN and Boosted Trees. In order to compare these models, paired t-test was applied on the model performance differences obtained from data resampling. Random Forests, Boosted Trees, Partial Least Square and GLMNet have superior overall performance, however they are only slightly higher than the other models. The comparative analysis also allowed us to define a relative variable importance as the average of variable importance from the different models. Two sets of variables are identified from this analysis. The first includes number of positive lymph nodes, tumor size, cancer grade and estrogen receptor, all has an important influence on model predictability. The second set incudes variables related to histological parameters and treatment types. The short term vs long term contribution of the clinical variables are also analyzed from the comparative models. From the various cancer treatment plans, the combination of Chemo/Radio therapy leads to the largest impact on cancer prognosis.

  8. Stage-specific predictive models for breast cancer survivability.

    Kate, Rohit J; Nadig, Ramya

    2017-01-01

    Survivability rates vary widely among various stages of breast cancer. Although machine learning models built in past to predict breast cancer survivability were given stage as one of the features, they were not trained or evaluated separately for each stage. To investigate whether there are differences in performance of machine learning models trained and evaluated across different stages for predicting breast cancer survivability. Using three different machine learning methods we built models to predict breast cancer survivability separately for each stage and compared them with the traditional joint models built for all the stages. We also evaluated the models separately for each stage and together for all the stages. Our results show that the most suitable model to predict survivability for a specific stage is the model trained for that particular stage. In our experiments, using additional examples of other stages during training did not help, in fact, it made it worse in some cases. The most important features for predicting survivability were also found to be different for different stages. By evaluating the models separately on different stages we found that the performance widely varied across them. We also demonstrate that evaluating predictive models for survivability on all the stages together, as was done in the past, is misleading because it overestimates performance. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  9. Molecular targets in urothelial cancer: detection, treatment, and animal models of bladder cancer

    Smolensky, Dmitriy; Rathore, Kusum; Cekanova, Maria

    2016-01-01

    Bladder cancer remains one of the most expensive cancers to treat in the United States due to the length of required treatment and degree of recurrence. In order to treat bladder cancer more effectively, targeted therapies are being investigated. In order to use targeted therapy in a patient, it is important to provide a genetic background of the patient. Recent advances in genome sequencing, as well as transcriptome analysis, have identified major pathway components altered in bladder cancer. The purpose of this review is to provide a broad background on bladder cancer, including its causes, diagnosis, stages, treatments, animal models, as well as signaling pathways in bladder cancer. The major focus is given to the PI3K/AKT pathway, p53/pRb signaling pathways, and the histone modification machinery. Because several promising immunological therapies are also emerging in the treatment of bladder cancer, focus is also given on general activation of the immune system for the treatment of bladder cancer. PMID:27784990

  10. Phenomenological modelling of second cancer incidence for radiation treatment planning

    Pfaffenberger, Asja; Oelfke, Uwe; Schneider, Uwe; Poppe, Bjoern

    2009-01-01

    It is still an unanswered question whether a relatively low dose of radiation to a large volume or a higher dose to a small volume produces the higher cancer incidence. This is of interest in view of modalities like IMRT or rotation therapy where high conformity to the target volume is achieved at the cost of a large volume of normal tissue exposed to radiation. Knowledge of the shape of the dose response for radiation-induced cancer is essential to answer the question of what risk of second cancer incidence is implied by which treatment modality. This study therefore models the dose response for radiation-induced second cancer after radiation therapy of which the exact mechanisms are still unknown. A second cancer risk estimation tool for treatment planning is presented which has the potential to be used for comparison of different treatment modalities, and risk is estimated on a voxel basis for different organs in two case studies. The presented phenomenological model summarises the impact of microscopic biological processes into effective parameters of mutation and cell sterilisation. In contrast to other models, the effective radiosensitivities of mutated and non-mutated cells are allowed to differ. Based on the number of mutated cells present after irradiation, the model is then linked to macroscopic incidence by summarising model parameters and modifying factors into natural cancer incidence and the dose response in the lower-dose region. It was found that all principal dose-response functions discussed in the literature can be derived from the model. However, from the investigation and due to scarcity of adequate data, rather vague statements about likelihood of dose-response functions can be made than a definite decision for one response. Based on the predicted model parameters, the linear response can probably be rejected using the dynamics described, but both a flattening response and a decrease appear likely, depending strongly on the effective cell

  11. Blood Vessel Normalization in the Hamster Oral Cancer Model for Experimental Cancer Therapy Studies

    Ana J. Molinari; Romina F. Aromando; Maria E. Itoiz; Marcela A. Garabalino; Andrea Monti Hughes; Elisa M. Heber; Emiliano C. C. Pozzi; David W. Nigg; Veronica A. Trivillin; Amanda E. Schwint

    2012-07-01

    Normalization of tumor blood vessels improves drug and oxygen delivery to cancer cells. The aim of this study was to develop a technique to normalize blood vessels in the hamster cheek pouch model of oral cancer. Materials and Methods: Tumor-bearing hamsters were treated with thalidomide and were compared with controls. Results: Twenty eight hours after treatment with thalidomide, the blood vessels of premalignant tissue observable in vivo became narrower and less tortuous than those of controls; Evans Blue Dye extravasation in tumor was significantly reduced (indicating a reduction in aberrant tumor vascular hyperpermeability that compromises blood flow), and tumor blood vessel morphology in histological sections, labeled for Factor VIII, revealed a significant reduction in compressive forces. These findings indicated blood vessel normalization with a window of 48 h. Conclusion: The technique developed herein has rendered the hamster oral cancer model amenable to research, with the potential benefit of vascular normalization in head and neck cancer therapy.

  12. A preclinical mouse model of invasive lobular breast cancer metastasis

    Doornebal, Chris W.; Klarenbeek, Sjoerd; Braumuller, Tanya M.; Klijn, Christiaan N.; Ciampricotti, Metamia; Hau, Cheei-Sing; Hollmann, Markus W.; Jonkers, Jos; de Visser, Karin E.

    2013-01-01

    Metastatic disease accounts for more than 90% of cancer-related deaths, but the development of effective antimetastatic agents has been hampered by the paucity of clinically relevant preclinical models of human metastatic disease. Here, we report the development of a mouse model of spontaneous

  13. Breast cancer cell lines: friend or foe?

    Burdall, Sarah E; Hanby, Andrew M; Lansdown, Mark RJ; Speirs, Valerie

    2003-01-01

    The majority of breast cancer research is conducted using established breast cancer cell lines as in vitro models. An alternative is to use cultures established from primary breast tumours. Here, we discuss the pros and cons of using both of these models in translational breast cancer research

  14. Establishment of an animal challenge model as a potency assay for an inactivated Enterovirus Type 71 vaccine.

    Wang, Kun-Teng; Lin, Shih-Jie; Wang, Hsiu-Chi; Chen, Pin-Chun; Lin, Jiao-Jung; Chiang, Jen-Ron; Chang, Chao-Liang; Shih, Daniel Yang-Chih; Lo, Chi-Fang; Wang, Der-Yuan

    2016-07-01

    Enterovirus 71 (EV71) belongs to the Enterovirus genus of the Picornaviridae family, and its occurrence in Asia is associated with hand-foot-and-mouth disease (HFMD), leading to death in some cases, in young children. An effective EV71 vaccine is therefore urgently needed. In this study, we established a two-step EV71 vaccine potency model. Intraperitoneal injections in 2-day-old suckling mice were used to establish the LD50 of EV71 B4, B5, C2, C4, and C5 subgenotypes. Only C4 caused hind limb paralysis in mice (LD50: 2.62 ± 0.45). EV71 VP1 protein was identified in the brain tissues at histology. In the second phase of the model, 3-week-old female ICR mice received one primary and two boosting i.p. injections of formalin-inactivated EV71 B4 and C4 vaccine. Immunized serum was neutralized in vitro with EV71 C4 and applied to the murine challenge model. The C4 vaccine-immunized serum exhibited the highest protective titre (ED50 = 114.6), while the B4 immunized serum had the weakest protective titre (ED50 = 34.3). Additionally, human plasma and intravenous immunoglobulin displayed significant protection in the neutralization assay. Our results could facilitate candidate EV71 vaccine immunogenicity and efficacy evaluations, and may help establish reference EV71 antisera in the future. Copyright © 2016 International Alliance for Biological Standardization. Published by Elsevier Ltd. All rights reserved.

  15. Mechanistic models for cancer development after short time radiation exposure

    Kottbauer, M. M.

    1997-12-01

    In this work two biological based models were developed. First the single-hit model for solid tumors (SHM-S) and second the single-hit model for leukemia (SHM-L). These models are a further development of the Armitage-Doll model for the special case of a short time radiation exposure. The basis of the models is the multistage process of carcinogeneses. The single-hit models provide simultaneously the age-dependent cancer-rate of spontaneous and radiation induced tumors as well as the dose-effect relationships at any age after exposure. The SHM-S leads to a biological based dose-effect relationship, which is similar to the relative risk model suggested by the ICRP 60. The SHM-S describes the increased mortality rate of the bomb survivors more accurate than the relative risk model. The SHM-L results in an additive dose-effect relationship. It is shown that only small differences in the derivation of the two models lead to the two dose-effect relationships. Beside the radiation exposure the new models consider the decrease of the cancer mortality rate at higher ages (age>75) which can be traced back mainly to three causes: competitive causes of death, reduction of cell proliferation and reduction of risk groups. The single-hit models also consider children cancer, the different rates of incidence and mortality, influence of the immune system and the cell-killing effect. (author)

  16. Model - SEO - serious ovarian cancer | Center for Cancer Research

    Genetically engineered mouse model Developed in house Genetic aberrations: Inactivation of Rb tumor suppression (via K18-T121 transgene) Tp53 loss or mutation (R172H) Brca1 or Brca2 loss Induction by injection of adenovirus expressing Cre recombinase under the ovrian bursa Pathology:

  17. New insights into the metastatic behavior after breast cancer surgery, according to well-established clinicopathological variables and molecular subtypes.

    Oreste Claudio Buonomo

    Full Text Available Despite advances in treatment, up to 30% of patients with early breast cancer (BC experience distant disease relapse. However, a comprehensive understanding of tumor spread and site-specific recurrence patterns remains lacking. This retrospective case-control study included 103 consecutive patients with metastatic BC admitted to our institution (2000-2013. Cases were matched according to age, tumor biology, and clinicopathological features to 221 patients with non-metastatic BC (control group. The median follow-up period among the 324 eligible patients was 7.3 years. While relatively low values for sensitivity (71% and specificity (56% were found for axillary lymph node (ALN involvement as an indicator of risk and pattern of distant relapse, nodal status remained the most powerful predictor of metastases (OR: 3.294; CL: 1.9-5.5. Rates of dissemination and metastatic efficiency differed according to molecular subtype. HER2-positive subtypes showed a stronger association with systemic spread (OR: 2.127; CL: 1.2-3.8 than other subgroups. Classification as Luminal or Non-Luminal showed an increased risk of lung and distant nodal recurrence, and a decreased risk in bone metastases in the Non-Luminal group (OR: 2.9, 3.345, and 0.2, respectively. Tumors with HER2 overexpression had a significantly high risk for distant relapse (OR: 2.127 compared with HER2-negative tumors and also showed higher central nervous system (CNS and lung metastatic potential (OR: 5.6 and 2.65, respectively and low risk of bone disease progression (OR: 0.294. Furthermore, we found significant associations between biological profiles and sites of recurrence. A new process of clinical/diagnostic staging, including molecular subtypes, could better predict the likelihood of distant relapses and their anatomical location. Recognition and appreciation of clinically distinct molecular subtypes may assist in evaluation of the probability of distant relapses and their sites. Our

  18. Establishing the distribution of satellite lesions in intermediate- and high-risk prostate cancer: implications for focused radiotherapy.

    Hegde, J V; Margolis, D J; Wang, P-C; Reiter, R E; Huang, J; Steinberg, M L; Kamrava, M

    2017-06-01

    In focused radiotherapy for prostate cancer (PC), a full dose of radiation is delivered to the index lesion while reduced dose is delivered to the remaining prostate to reduce morbidity. As PC is commonly multifocal, we investigated whether baseline clinical characteristics or multiparametric magnetic resonance imaging (mpMRI) may be useful to predict the actual pathologic distribution of PC in men with intermediate- or high-risk PC, which may better inform how to deliver focused radiotherapy. A retrospective single-institutional study was performed on 71 consecutive men with clinically localized, intermediate- or high-risk PC who underwent mpMRI followed by radical prostatectomy (RP) from January 2012 to December 2012. Logistic regression analysis was performed to evaluate preoperative predictors for satellite lesions. Performance characteristics of mpMRI to detect satellite lesions and the extent of prostate disease (one hemi-gland vs both) were also evaluated. In all, 50.7% had satellite lesions on mpMRI. On RP specimen analysis, 66.2% had satellite lesions and 55.3% of these satellite lesions had pathologic Gleason score (pGS)⩾3+4. The sensitivity, specificity, positive predictive value, negative predictive value and accuracy for mpMRI detecting a satellite lesion being present in the RP specimen were 59.6%, 66.7%, 77.8%, 45.7% and 62.0%, respectively. The presence of MRI satellite lesions was the only preoperative predictor significantly associated with finding satellite lesions on final pathology (hazard ratio (HR), 2.95, P=0.040). There was agreement in 76.1% of the entire cohort for unilateral vs bilateral disease when incorporating both biopsy and mpMRI information and comparing with the RP specimen. In intermediate risk or greater PC, only the presence of mpMRI satellite lesions could predict for pathologic satellite lesions. While combining biopsy and mpMRI information may improve preoperative disease localization, the relatively high incidence of

  19. A prospective multiple case study of the impact of emerging scientific evidence on established colorectal cancer screening programs: a study protocol.

    Geddie, Hannah; Dobrow, Mark J; Hoch, Jeffrey S; Rabeneck, Linda

    2012-06-01

    Health-policy decision making is a complex and dynamic process, for which strong evidentiary support is required. This includes scientifically produced research, as well as information that relates to the context in which the decision takes place. Unlike scientific evidence, this "contextual evidence" is highly variable and often includes information that is not scientifically produced, drawn from sources such as political judgement, program management experience and knowledge, or public values. As the policy decision-making process is variable and difficult to evaluate, it is often unclear how this heterogeneous evidence is identified and incorporated into "evidence-based policy" decisions. Population-based colorectal cancer screening poses an ideal context in which to examine these issues. In Canada, colorectal cancer screening programs have been established in several provinces over the past five years, based on the fecal occult blood test (FOBT) or the fecal immunochemical test. However, as these programs develop, new scientific evidence for screening continues to emerge. Recently published randomized controlled trials suggest that the use of flexible sigmoidoscopy for population-based screening may pose a greater reduction in mortality than the FOBT. This raises the important question of how policy makers will address this evidence, given that screening programs are being established or are already in place. This study will examine these issues prospectively and will focus on how policy makers monitor emerging scientific evidence and how both scientific and contextual evidence are identified and applied for decisions about health system improvement. This study will employ a prospective multiple case study design, involving participants from Ontario, Alberta, Manitoba, Nova Scotia, and Quebec. In each province, data will be collected via document analysis and key informant interviews. Documents will include policy briefs, reports, meeting minutes, media

  20. An integrated model for radiation induced cancer

    Hall, E.J.; Varma, M.

    1994-01-01

    Risk estimates for radiation induced cancer are based on epidemiological data, principally the Japanese A bomb survivors. These estimates for radiation are better known than for any other environmental pollutant, but they do not relate directly to exposure to low doses and low dose rate. Recent rapid advances in molecular genetics, coupled with steady gains in cellular biology, radiation physics and chemistry led to the notion that the time may not be far off when it may be possible to arrive at human cancer risk estimates entirely from laboratory data. Whether risk estimates based on laboratory data will ever replace estimates based on epidemiological studies is an open question. What is clear is that laboratory data can supplement the present risk estimates by providing information on the relative effectiveness of high LET radiations, the importance of dose rate and dose protraction, and by identifying subpopulations which are unusually sensitive or resistant to radiation carcinogenesis. (author)

  1. [Establishment of the mathematic model of total quantum statistical moment standard similarity for application to medical theoretical research].

    He, Fu-yuan; Deng, Kai-wen; Huang, Sheng; Liu, Wen-long; Shi, Ji-lian

    2013-09-01

    The paper aims to elucidate and establish a new mathematic model: the total quantum statistical moment standard similarity (TQSMSS) on the base of the original total quantum statistical moment model and to illustrate the application of the model to medical theoretical research. The model was established combined with the statistical moment principle and the normal distribution probability density function properties, then validated and illustrated by the pharmacokinetics of three ingredients in Buyanghuanwu decoction and of three data analytical method for them, and by analysis of chromatographic fingerprint for various extracts with different solubility parameter solvents dissolving the Buyanghanwu-decoction extract. The established model consists of four mainly parameters: (1) total quantum statistical moment similarity as ST, an overlapped area by two normal distribution probability density curves in conversion of the two TQSM parameters; (2) total variability as DT, a confidence limit of standard normal accumulation probability which is equal to the absolute difference value between the two normal accumulation probabilities within integration of their curve nodical; (3) total variable probability as 1-Ss, standard normal distribution probability within interval of D(T); (4) total variable probability (1-beta)alpha and (5) stable confident probability beta(1-alpha): the correct probability to make positive and negative conclusions under confident coefficient alpha. With the model, we had analyzed the TQSMS similarities of pharmacokinetics of three ingredients in Buyanghuanwu decoction and of three data analytical methods for them were at range of 0.3852-0.9875 that illuminated different pharmacokinetic behaviors of each other; and the TQSMS similarities (ST) of chromatographic fingerprint for various extracts with different solubility parameter solvents dissolving Buyanghuanwu-decoction-extract were at range of 0.6842-0.999 2 that showed different constituents

  2. Predicting Cortisol Exposure from Paediatric Hydrocortisone Formulation Using a Semi-Mechanistic Pharmacokinetic Model Established in Healthy Adults.

    Melin, Johanna; Parra-Guillen, Zinnia P; Hartung, Niklas; Huisinga, Wilhelm; Ross, Richard J; Whitaker, Martin J; Kloft, Charlotte

    2018-04-01

    Optimisation of hydrocortisone replacement therapy in children is challenging as there is currently no licensed formulation and dose in Europe for children under 6 years of age. In addition, hydrocortisone has non-linear pharmacokinetics caused by saturable plasma protein binding. A paediatric hydrocortisone formulation, Infacort ® oral hydrocortisone granules with taste masking, has therefore been developed. The objective of this study was to establish a population pharmacokinetic model based on studies in healthy adult volunteers to predict hydrocortisone exposure in paediatric patients with adrenal insufficiency. Cortisol and binding protein concentrations were evaluated in the absence and presence of dexamethasone in healthy volunteers (n = 30). Dexamethasone was used to suppress endogenous cortisol concentrations prior to and after single doses of 0.5, 2, 5 and 10 mg of Infacort ® or 20 mg of Infacort ® /hydrocortisone tablet/hydrocortisone intravenously. A plasma protein binding model was established using unbound and total cortisol concentrations, and sequentially integrated into the pharmacokinetic model. Both specific (non-linear) and non-specific (linear) protein binding were included in the cortisol binding model. A two-compartment disposition model with saturable absorption and constant endogenous cortisol baseline (Baseline cort ,15.5 nmol/L) described the data accurately. The predicted cortisol exposure for a given dose varied considerably within a small body weight range in individuals weighing cortisol exposure indicated the importance of defining an accurate hydrocortisone dose to mimic physiological concentrations for neonates and infants weighing <20 kg. EudraCT number: 2013-000260-28, 2013-000259-42.

  3. Simulation models in population breast cancer screening: A systematic review.

    Koleva-Kolarova, Rositsa G; Zhan, Zhuozhao; Greuter, Marcel J W; Feenstra, Talitha L; De Bock, Geertruida H

    2015-08-01

    The aim of this review was to critically evaluate published simulation models for breast cancer screening of the general population and provide a direction for future modeling. A systematic literature search was performed to identify simulation models with more than one application. A framework for qualitative assessment which incorporated model type; input parameters; modeling approach, transparency of input data sources/assumptions, sensitivity analyses and risk of bias; validation, and outcomes was d