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Sample records for cancer dbcg 89c

  1. DBCG trial 89B comparing adjuvant CMF and ovarian ablation: similar outcome for eligible but non-enrolled and randomized breast cancer patients

    DEFF Research Database (Denmark)

    Ejlertsen, B.; Jensen, M.B.; Mouridsen, H.T.

    2008-01-01

    INTRODUCTION: A cohort of premenopausal patients with primary hormone receptor positive breast cancer was prospectively identified to be eligible for the DBCG 89B trial. We perform a long-term follow-up and evaluate the external validity of the trial. MATERIAL AND METHODS: Following registration...

  2. The value of TOP2A gene copy number variation as a biomarker in breast cancer: Update of DBCG trial 89D

    DEFF Research Database (Denmark)

    Nielsen, K.V.; Ejlertsen, B.; Moller, S.

    2008-01-01

    BACKGROUND: Previous analyses of TOP2A and HER2 in the Danish Breast Cancer Coopererative Group (DBCG) trial 89D suggested that TOP2A amplifications and possible also deletions are predictive markers for the effect of adjuvant epirubicin in patients with primary breast cancer. We present an updated......% reduction in the risk of an event (p=0.002) and a 51% reduction in the risk of death (p=0.01) if allocated to CEF compared to 6% and 10% in TOP2A normal patients. A similar but non-significant trend (p=0.08) was shown in patients with TOP2A deletions. Clear statistical evidence of a differential benefit......, favoring CEF among patients with TOP2A aberrations was found for RFS (p=0.02 for interaction) but not for OS (p=0.14 for interaction). CONCLUSION: In conclusion, this updated analysis of TOP2A aberrations in DBCG trial 89D suggests a differential benefit of adjuvant chemotherapy in patients with primary...

  3. Failure pattern and survival after breast conserving therapy. Long-term results of the Danish Breast Cancer Group (DBCG) 89 TM cohort

    DEFF Research Database (Denmark)

    Lyngholm, C D; Laurberg, T; Alsner, J

    2016-01-01

    -year overall survival (OS) and recurrence-free survival were 63.7% and 43.1%, respectively. Subdivided by age groups cumulative incidences at 20 years were LR: 18.9%, 10.5% and 12.4%, and DSM: 28.9%, 18.9% and 28.4% in young (≤45 years), middle-aged (46–55 years) and older (≥56 years) women, respectively....... Data from the DBCG database were completed via search through the Danish Pathology Data Bank and medical records. Results: Median follow-up time was 17 years. At 20 years the cumulative incidences of local recurrence (LR) and disease-specific mortality (DSM) were 15.3% and 25.8%, respectively. Twenty....... In an adjusted analysis age maintained a significant and independent effect on both LR and DSM. Conclusion: The DBCG 82 TM program was successfully implemented. The women treated with BCT in the DBCG 89 program displayed equal failure pattern and improved survival in comparison with women from the DBCG 82 TM...

  4. Estrogen receptor, Progesterone receptor, HER2 status and Ki67 index and responsiveness to adjuvant tamoxifen in postmenopausal high-risk breast cancer patients enrolled in the DBCG 77C trial

    DEFF Research Database (Denmark)

    Knoop, Ann; Lænkholm, Anne Vibeke; Jensen, M. B.

    2014-01-01

    BCRR and BCM in postmenopausal patients with ER positive breast cancers. The relative benefit from tamoxifen was not significantly different in luminal A and B subtypes. Funding: The Danish Breast Cancer Cooperative Group (DBCG) prepared the original protocol (DBCG 77C) and was the sponsor of the study......Background: The DBCG 77C trial compared one year of tamoxifen in postmenopausal, steroid-receptor unknown, high-risk breast cancer patients to no adjuvant systemic therapy. After a potential follow-up of 30 years we report overall efficacy of the study and results according to subtypes subsequently...... assessed by immunohistochemistry and fluorescent in situ hybridisation (FISH). Methods: Between 1977 and 1982, 1716 postmenopausal patients with tumours larger than 5 cm or positive axillary nodes were randomly assigned to no systemic therapy or tamoxifen 30 mg daily for one year. Archival tumour tissue...

  5. Risk of second primary cancer among patients with early operable breast cancer registered or randomised in Danish Breast Cancer cooperative Group (DBCG) protocols of the 77, 82 and 89 programmes during 1977-2001

    DEFF Research Database (Denmark)

    Andersson, M.; Jensen, Maiken Brit; Engholm, G.

    2008-01-01

    Breast cancer survivors have increased risks of developing second primary cancers due to shared etiology, life style factors but also to primary breast cancer treatment. Among 53 418 patients registered by the population based Danish Breast Cancer Cooperative Group (DBCG) during 1977-2001, 31 818...... patients were treated and followed according to guidelines of DBCG. In addition to surgery 23% received tamoxifen, 23% chemotherapy and 35% radiotherapy as treatment for primary breast cancer. Second primary cancers were identified by linkage to the population based Danish Cancer Register. Cancer incidence...... rates of the Danish population were used for calculation of standardized incidence ratios (SIRs). Time at risk was from diagnosis of breast cancer+1 year until death or through 2002. Risk for all second primary cancers combined was increased, SIR=1.04 (95% confidence interval 0.99-1.08). Sites...

  6. Adjuvant chemotherapy in early breast cancer.

    Science.gov (United States)

    Ejlertsen, Bent

    2016-05-01

    With long-term follow-up, the DBCG 77B trial demonstrates that oral single-agent cyclophosphamide significantly reduces the risk of recurrence and mortality as compared with no systemic therapy in pre-menopausal patients with high-risk early breast cancer. DBCG 77B is the only randomised trial assessing single-agent cyclophosphamide; and a second comparison suggests that its benefits are comparable to what may be achieved by classic CMF. The lack of benefits from adding methotrexate and fluorouracil to cyclophosphamide paved the way for combining cyclophosphamide with anthracyclines and later taxanes. DBCG 89D showed an incremental benefit in DFS and OS from substituting methotrexate with epirubicin. The advantage of anthracycline-containing three-drug combinations over CMF was confirmed by others and in the individual-patient EBCTCG meta-analysis, while standard AC or EC for four cycles not was superior to classic CMF. A further reduction in breast cancer mortality appeared in the EBCTCG meta-analysis from the addition of a taxane to a standard AC, while the substitution of cycles or drugs with a taxane was not associated with a reduction in mortality. No apparent benefit was observed in an early analysis of the DBCG 82C evaluating the addition of CMF to tamoxifen in post-menopausal high-risk breast cancer patients. Apart from menopausal status, the two trials had identical selection criteria, and the differences in outcome warranted a long-term follow-up of the 82C trial. After ten years of follow-up, CMF in the DBCG 82C was associated with a significant improvement in DFS; but even with 24 years of follow-up, mortality was not significantly improved. The diversity in outcome from the 77C and the 82B trials triggered further studies. The 77B trial used classic CMF with oral cyclophospamide, while a four-weekly intravenous CMF regimen was used in the 82B and C trials, and a three-weekly CMF regimen was used in the succeeding 89B and D trials. The outcome following

  7. Impact of BCL2 and p53 on postmastectomy radiotherapy response in high-risk breast cancer. A subgroup analysis of DBCG82 b&c

    DEFF Research Database (Denmark)

    Kyndi, Marianne; Sørensen, Flemming Brandt; Knudsen, Helle

    2008-01-01

    -Meier probability plots showed a significantly improved overall survival after PMRT for the BCL2 positive subgroup, whereas practically no survival improvement was seen after PMRT for the BCL2 negative subgroup. In multivariate analysis of OS, however, no significant interaction was found between BCL2......PURPOSE: To examine p53 and BCL2 expression in high-risk breast cancer patients randomized to postmastectomy radiotherapy (PMRT). PATIENTS AND METHODS: The present analysis included 1 000 of 3 083 high-risk breast cancer patients randomly assigned to PMRT in the DBCG82 b&c studies. Tissue...... tests, Kaplan-Meier probability plots, Log-rank test, and Cox univariate and multivariate regression analyses. RESULTS: p53 accumulation was not significantly associated with increased overall mortality, DM or LRR probability in univariate or multivariate Cox regression analyses. Kaplan...

  8. Validity of Danish Breast Cancer Group (DBCG) registry data used in the predictors of breast cancer recurrence (ProBeCaRe) premenopausal breast cancer cohort study

    DEFF Research Database (Denmark)

    Cronin-Fenton, Deirdre P; Kjærsgaard, Anders; Ahern, Thomas P

    2017-01-01

    BACKGROUND: Validation studies of the Danish Breast Cancer Group (DBCG) registry show good agreement with medical records for adjuvant treatment data, but inconsistent recurrence information. No studies have validated changes in menopausal status or endocrine therapy during follow-up. In a longit...

  9. Development and validation of a gene profile predicting benefit of postmastectomy radiotherapy in patients with high-risk breast cancer: a study of gene expression in the DBCG82bc cohort.

    Science.gov (United States)

    Tramm, Trine; Mohammed, Hayat; Myhre, Simen; Kyndi, Marianne; Alsner, Jan; Børresen-Dale, Anne-Lise; Sørlie, Therese; Frigessi, Arnoldo; Overgaard, Jens

    2014-10-15

    To identify genes predicting benefit of radiotherapy in patients with high-risk breast cancer treated with systemic therapy and randomized to receive or not receive postmastectomy radiotherapy (PMRT). The study was based on the Danish Breast Cancer Cooperative Group (DBCG82bc) cohort. Gene-expression analysis was performed in a training set of frozen tumor tissue from 191 patients. Genes were identified through the Lasso method with the endpoint being locoregional recurrence (LRR). A weighted gene-expression index (DBCG-RT profile) was calculated and transferred to quantitative real-time PCR (qRT-PCR) in corresponding formalin-fixed, paraffin-embedded (FFPE) samples, before validation in FFPE from 112 additional patients. Seven genes were identified, and the derived DBCG-RT profile divided the 191 patients into "high LRR risk" and "low LRR risk" groups. PMRT significantly reduced risk of LRR in "high LRR risk" patients, whereas "low LRR risk" patients showed no additional reduction in LRR rate. Technical transfer of the DBCG-RT profile to FFPE/qRT-PCR was successful, and the predictive impact was successfully validated in another 112 patients. A DBCG-RT gene profile was identified and validated, identifying patients with very low risk of LRR and no benefit from PMRT. The profile may provide a method to individualize treatment with PMRT. ©2014 American Association for Cancer Research.

  10. Tamoxifen for one year versus two years versus 6 months of Tamoxifen and 6 months of megestrol acetate: A randomized comparison in postmenopausal patients with high-risk breast cancer (DBCG 89C)

    DEFF Research Database (Denmark)

    Andersen, Jørn; Kamby, C.; Ejlertsen, B.

    2008-01-01

    From January 1, 1990 to December 31, 1994, DBCG conducted a randomised trial in 1 615 postmenopausal women with operable, high-risk, receptor-positive or -unknown breast cancer. The patients were after surgery randomised to Tamoxifen for 1 year (TAM1), Tamoxifen for 2 years (TAM 2) or Tamoxifen...... for 6 months followed by megestrol acetate for 6 months (TAM/MA). When the preplanned sample size of 1 500 patients was reached it was decided to continue randomisation to TAM1 or TAM2 and the study was finally closed December 31, 1996. With a median follow-up of more than 10 years...... in hazard ratios for DFS or OS among the three arms. Sideeffects were rare but more common in the TAM2 and TAM/MA arms Udgivelsesdato: 2008...

  11. Impact of BCL2 and p53 on postmastectomy radiotherapy response in high-risk breast cancer. A subgroup analysis of DBCG82 b

    DEFF Research Database (Denmark)

    Kyndi, M.; Sorensen, F.B.; Alsner, J.

    2008-01-01

    -Meier probability plots showed a significantly improved overall survival after PMRT for the BCL2 positive subgroup, whereas practically no survival improvement was seen after PMRT for the BCL2 negative subgroup. In multivariate analysis of OS, however, no significant interaction was found between BCL2......Purpose. To examine p53 and BCL2 expression in high-risk breast cancer patients randomized to postmastectomy radiotherapy (PMRT). Patients and methods. The present analysis included 1000 of 3 083 high-risk breast cancer patients randomly assigned to PMRT in the DBCG82 b&c studies. Tissue microarray......, Kaplan-Meier probability plots, Log-rank test, and Cox univariate and multivariate regression analyses. Results. p53 accumulation was not significantly associated with increased overall mortality, DM or LRR probability in univariate or multivariate Cox regression analyses. Kaplan-Meier probability plots...

  12. Adjuvant chemotherapy in early breast cancer

    DEFF Research Database (Denmark)

    Ejlertsen, Bent

    2016-01-01

    With long-term follow-up, the DBCG 77B trial demonstrates that oral single-agent cyclophosphamide significantly reduces the risk of recurrence and mortality as compared with no systemic therapy in pre-menopausal patients with high-risk early breast cancer. DBCG 77B is the only randomised trial...... not was superior to classic CMF. A further reduction in breast cancer mortality appeared in the EBCTCG meta-analysis from the addition of a taxane to a standard AC, while the substitution of cycles or drugs with a taxane was not associated with a reduction in mortality. No apparent benefit was observed in an early...... analysis of the DBCG 82C evaluating the addition of CMF to tamoxifen in post-menopausal high-risk breast cancer patients. Apart from menopausal status, the two trials had identical selection criteria, and the differences in outcome warranted a long-term follow-up of the 82C trial. After ten years of follow...

  13. Impact of BCL2 and p53 on postmastectomy radiotherapy response in high-risk breast cancer. A subgroup analysis of DBCG82 b and c

    International Nuclear Information System (INIS)

    Kyndi, M.; Alsner, J.; Nielsen, H.M.; Overgaard, J.; Soerensen, F.B.; Knudsen, H.; Overgaard, M.

    2008-01-01

    Purpose. To examine p53 and BCL2 expression in high-risk breast cancer patients randomized to postmastectomy radiotherapy (PMRT). Patients and methods. The present analysis included 1 000 of 3 083 high-risk breast cancer patients randomly assigned to PMRT in the DBCG82 b and c studies. Tissue microarray sections were stained with immunohistochemistry for p53 and BCL2. Median potential follow-up was 17 years. Clinical endpoints were locoregional recurrence (LRR), distant metastases (DM), overall mortality, and overall survival (OS). Statistical analyses included Kappa statistics, χ2 or exact tests, Kaplan-Meier probability plots, Log-rank test, and Cox univariate and multivariate regression analyses. Results. p53 accumulation was not significantly associated with increased overall mortality, DM or LRR probability in univariate or multivariate Cox regression analyses. Kaplan-Meier probability plots showed reduced OS and improved DM and LRR probabilities after PMRT within subgroups of both p53 negative and p53 positive patients. Negative BCL2 expression was significantly associated with increased overall mortality, DM and LRR probability in multivariate Cox regression analyses. Kaplan-Meier probability plots showed a significantly improved overall survival after PMRT for the BCL2 positive subgroup, whereas practically no survival improvement was seen after PMRT for the BCL2 negative subgroup. In multivariate analysis of OS, however, no significant interaction was found between BCL2 and randomization status. Significant reductions in LRR probability after PMRT were recorded within both the BCL2 positive and BCL2 negative subgroups. Conclusion. p53 was not associated with survival after radiotherapy in high-risk breast cancer, but BCL2 might be

  14. The clinical database and implementation of treatment guidelines by the Danish Breast Cancer Cooperative Group in 2007-2016

    DEFF Research Database (Denmark)

    Jensen, Maj-Britt; Laenkholm, Anne-Vibeke; Offersen, Birgitte V

    2018-01-01

    BACKGROUND: Since 40 years, Danish Breast Cancer Cooperative Group (DBCG) has provided comprehensive guidelines for diagnosis and treatment of breast cancer. This population-based analysis aimed to describe the plurality of modifications introduced over the past 10 years in the national Danish...... guidelines for the management of early breast cancer. By use of the clinical DBCG database we analyze the effectiveness of the implementation of guideline revisions in Denmark. METHODS: From the DBCG guidelines we extracted modifications introduced in 2007-2016 and selected examples regarding surgery......, radiotherapy (RT) and systemic treatment. We assessed introduction of modifications from release on the DBCG webpage to change in clinical practice using the DBCG clinical database. RESULTS: Over a 10-year period data from 48,772 patients newly diagnosed with malignant breast tumors were entered into DBCG...

  15. Concurrent new drug prescriptions and prognosis of early breast cancer

    DEFF Research Database (Denmark)

    Cronin-Fenton, Deirdre; Lash, Timothy L; Ahern, Thomas P

    2018-01-01

    Breast Cancer Group (DBCG) clinical database provides high-quality prospectively collected data on breast cancer diagnosis, treatment, and routine follow-up for breast cancer recurrence. Individual-level linkage of DBCG data to other population-based and medical registries in Denmark, including......BACKGROUND: Myriad reports suggest that frequently used prescription drugs alter the viability of breast cancer cells in pre-clinical studies. Routine use of these drugs, therefore, may impact breast cancer prognosis, and could have important implications for public health. METHODS: The Danish...... the Danish National Prescription Registry, has facilitated large population-based pharmacoepidemiology studies. A unique advantage of using DBCG data for such studies is the ability to investigate the association of drugs with breast cancer recurrence rather than breast cancer mortality - which may...

  16. {sup 89}Zr-Onartuzumab PET imaging of c-MET receptor dynamics

    Energy Technology Data Exchange (ETDEWEB)

    Pool, Martin; Kol, Arjan; Giesen, Danique; Vries, Elisabeth G.E. de [University of Groningen, Department of Medical Oncology, University Medical Center Groningen, Groningen (Netherlands); Terwisscha van Scheltinga, Anton G.T. [University of Groningen, Department of Clinical Pharmacy and Pharmacology, University Medical Center Groningen, Groningen (Netherlands); Lub-de Hooge, Marjolijn N. [University of Groningen, Department of Clinical Pharmacy and Pharmacology, University Medical Center Groningen, Groningen (Netherlands); University of Groningen, Department of Nuclear Medicine and Molecular Imaging, University Medical Center Groningen, Groningen (Netherlands)

    2017-08-15

    c-MET and its ligand hepatocyte growth factor are often dysregulated in human cancers. Dynamic changes in c-MET expression occur and might predict drug efficacy or emergence of resistance. Noninvasive visualization of c-MET dynamics could therefore potentially guide c-MET-directed therapies. We investigated the feasibility of {sup 89}Zr-labelled one-armed c-MET antibody onartuzumab PET for detecting relevant changes in c-MET levels induced by c-MET-mediated epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor erlotinib resistance or heat shock protein-90 (HSP90) inhibitor NVP-AUY-922 treatment in human non-small-cell lung cancer (NSCLC) xenografts. In vitro membrane c-MET levels were determined by flow cytometry. HCC827ErlRes, an erlotinib-resistant clone with c-MET upregulation, was generated from the exon-19 EGFR-mutant human NSCLC cell line HCC827. Mice bearing HCC827 and HCC827ErlRes tumours in opposite flanks underwent {sup 89}Zr-onartuzumab PET scans. The HCC827-xenografted mice underwent {sup 89}Zr-onartuzumab PET scans before treatment and while receiving biweekly intraperitoneal injections of 100 mg/kg NVP-AUY-922 or vehicle. Ex vivo, tumour c-MET immunohistochemistry was correlated with the imaging results. In vitro, membrane c-MET was upregulated in HCC827ErlRes tumours by 213 ± 44% in relation to the level in HCC827 tumours, while c-MET was downregulated by 69 ± 9% in HCC827 tumours following treatment with NVP-AUY-922. In vivo, {sup 89}Zr-onartuzumab uptake was 26% higher (P < 0.05) in erlotinib-resistant HCC827ErlRes than in HCC827 xenografts, while HCC827 tumour uptake was 33% lower (P < 0.001) following NVP-AUY-922 treatment. The results show that {sup 89}Zr-onartuzumab PET effectively discriminates relevant changes in c-MET levels and could potentially be used clinically to monitor c-MET status. (orig.)

  17. Danish Breast Cancer Cooperative Group

    DEFF Research Database (Denmark)

    Christiansen, Peer; Ejlertsen, Bent; Jensen, Maj-Britt

    2016-01-01

    AIM OF DATABASE: Danish Breast Cancer Cooperative Group (DBCG), with an associated database, was introduced as a nationwide multidisciplinary group in 1977 with the ultimate aim to improve the prognosis in breast cancer. Since then, the database has registered women diagnosed with primary invasive...... nonmetastatic breast cancer. The data reported from the departments to the database included details of the characteristics of the primary tumor, of surgery, radiotherapy, and systemic therapies, and of follow-up reported on specific forms from the departments in question. DESCRIPTIVE DATA: From 1977 through...... 2014, ~110,000 patients are registered in the nationwide, clinical database. The completeness has gradually improved to more than 95%. DBCG has continuously prepared evidence-based guidelines on diagnosis and treatment of breast cancer and conducted quality control studies to ascertain the degree...

  18. DBCG hypo trial validation of radiotherapy parameters from a national data bank versus manual reporting.

    Science.gov (United States)

    Brink, Carsten; Lorenzen, Ebbe L; Krogh, Simon Long; Westberg, Jonas; Berg, Martin; Jensen, Ingelise; Thomsen, Mette Skovhus; Yates, Esben Svitzer; Offersen, Birgitte Vrou

    2018-01-01

    The current study evaluates the data quality achievable using a national data bank for reporting radiotherapy parameters relative to the classical manual reporting method of selected parameters. The data comparison is based on 1522 Danish patients of the DBCG hypo trial with data stored in the Danish national radiotherapy data bank. In line with standard DBCG trial practice selected parameters were also reported manually to the DBCG database. Categorical variables are compared using contingency tables, and comparison of continuous parameters is presented in scatter plots. For categorical variables 25 differences between the data bank and manual values were located. Of these 23 were related to mistakes in the manual reported value whilst the remaining two were a wrong classification in the data bank. The wrong classification in the data bank was related to lack of dose information, since the two patients had been treated with an electron boost based on a manual calculation, thus data was not exported to the data bank, and this was not detected prior to comparison with the manual data. For a few database fields in the manual data an ambiguity of the parameter definition of the specific field is seen in the data. This was not the case for the data bank, which extract all data consistently. In terms of data quality the data bank is superior to manually reported values. However, there is a need to allocate resources for checking the validity of the available data as well as ensuring that all relevant data is present. The data bank contains more detailed information, and thus facilitates research related to the actual dose distribution in the patients.

  19. 89Zr-huJ591 immuno-PET imaging in patients with advanced metastatic prostate cancer

    International Nuclear Information System (INIS)

    Pandit-Taskar, Neeta; Solomon, Stephen B.; Durack, Jeremy C.; Carrasquillo, Jorge A.; Lefkowitz, Robert A.; Osborne, Joseph R.; O'Donoghue, Joseph A.; Beylergil, Volkan; Ruan, Shutian; Cheal, Sarah M.; Lyashchenko, Serge; Gonen, Mithat; Lewis, Jason S.; Holland, Jason P.; Reuter, Victor E.; Loda, Massimo F.; Smith-Jones, Peter M.; Weber, Wolfgang A.; Larson, Steven M.; Bander, Neil H.; Scher, Howard I.; Morris, Michael J.

    2014-01-01

    Given the bone tropism of prostate cancer, conventional imaging modalities poorly identify or quantify metastatic disease. 89 Zr-huJ591 positron emission tomography (PET) imaging was performed in patients with metastatic prostate cancer to analyze and validate this as an imaging biomarker for metastatic disease. The purpose of this initial study was to assess safety, biodistribution, normal organ dosimetry, and optimal imaging time post-injection for lesion detection. Ten patients with metastatic prostate cancer received 5 mCi of 89 Zr-huJ591. Four whole-body scans with multiple whole-body count rate measurements and serum activity concentration measurements were obtained in all patients. Biodistribution, clearance, and lesion uptake by 89 Zr-huJ591 immuno-PET imaging was analyzed and dosimetry was estimated using MIRD techniques. Initial assessment of lesion targeting of 89 Zr-huJ591 was done. Optimal time for imaging post-injection was determined. The dose was well tolerated with mild chills and rigors seen in two patients. The clearance of 89 Zr-huJ591 from serum was bi-exponential with biological half-lives of 7 ± 4.5 h (range 1.1-14 h) and 62 ± 13 h (range 51-89 h) for initial rapid and later slow phase. Whole-body biological clearance was 219 ± 48 h (range 153-317 h). The mean whole-body and liver residence time was 78.7 and 25.6 h, respectively. Dosimetric estimates to critical organs included liver 7.7 ± 1.5 cGy/mCi, renal cortex 3.5 ± 0.4 cGy/mCi, and bone marrow 1.2 ± 0.2 cGy/mCi. Optimal time for patient imaging after injection was 7 ± 1 days. Lesion targeting of bone or soft tissue was seen in all patients. Biopsies were performed in 8 patients for a total 12 lesions, all of which were histologically confirmed as metastatic prostate cancer. One biopsy-proven lesion was not positive on 89 Zr-huJ591, while the remaining 11 lesions were 89 Zr-huJ591 positive. Two biopsy-positive nodal lesions were noted only on 89 Zr-huJ591 study, while the

  20. Is the benefit of postmastectomy irradiation limited to patients with four or more positive nodes, as recommended in international consensus reports? A subgroup analysis of the DBCG 82 b & c randomized trials

    DEFF Research Database (Denmark)

    Overgaard, Marie; Nielsen, Hanne Melgaard; Overgaard, Jens

    2007-01-01

    % to 10% (p4% (p...BACKGROUND AND AIM: Numerous consensus reports recommend that postmastectomy radiotherapy (RT) in addition to systemic therapy is indicated in high-risk patients with 4+ positive nodes, but not in patients with 1-3 positive nodes. A subgroup analysis of the DBCG 82 b&c trials was performed...... lymph nodes removed (median 7), the present analysis was limited to 1152 node positive patients with 8 or more nodes removed. RESULTS: The overall 15-year survival rate in the subgroup was 39% and 29% (p=0.015) after RT and no RT, respectively. RT reduced the 15-year loco-regional failure rate from 51...

  1. {sup 89}Zr-huJ591 immuno-PET imaging in patients with advanced metastatic prostate cancer

    Energy Technology Data Exchange (ETDEWEB)

    Pandit-Taskar, Neeta; Solomon, Stephen B.; Durack, Jeremy C.; Carrasquillo, Jorge A.; Lefkowitz, Robert A.; Osborne, Joseph R. [Memorial Sloan Kettering Cancer Center, Department of Radiology, New York, NY (United States); Weill Cornell Medical College, Department of Radiology, New York, NY (United States); O' Donoghue, Joseph A. [Memorial Sloan Kettering Cancer Center, Department of Medical Physics, New York, NY (United States); Beylergil, Volkan; Ruan, Shutian; Cheal, Sarah M. [Memorial Sloan Kettering Cancer Center, Department of Radiology, New York, NY (United States); Lyashchenko, Serge [Memorial Sloan Kettering Cancer Center, Department of Radiochemistry and Molecular Imaging Probes Core, New York, NY (United States); Gonen, Mithat [Memorial Sloan Kettering Cancer Center, Department of Epidemiology and Biostatistics, New York, NY (United States); Lewis, Jason S. [Memorial Sloan Kettering Cancer Center, Department of Radiology, New York, NY (United States); Memorial Sloan Kettering Cancer Center, Department of Radiochemistry and Molecular Imaging Probes Core, New York, NY (United States); Memorial Sloan Kettering Cancer Center, Program in Molecular Pharmacology and Chemistry, New York, NY (United States); Weill Cornell Medical College, Department of Radiology, New York, NY (United States); Holland, Jason P. [Memorial Sloan Kettering Cancer Center, Department of Radiology, New York, NY (United States); Harvard Medical School, Department of Radiology of Massachusetts General Hospital, Boston, MA (United States); Reuter, Victor E. [Memorial Sloan Kettering Cancer Center, Department of Pathology, New York, NY (United States); Weill Cornell Medical College, Department of Pathology, New York, NY (United States); Loda, Massimo F. [Dana-Farber Cancer Institute, Boston, MA (United States); Broad Institute of Harvard and MIT, Cambridge, MA (United States); Smith-Jones, Peter M. [Memorial Sloan Kettering Cancer Center, Department of Radiology, New York, NY (United States); Department of Psychiatry and Behavioral Science of Stony Brook University, Stony Brook, NY (United States); Weber, Wolfgang A.; Larson, Steven M. [Memorial Sloan Kettering Cancer Center, Department of Radiology, New York, NY (United States); Memorial Sloan Kettering Cancer Center, Program in Molecular Pharmacology and Chemistry, New York, NY (United States); Weill Cornell Medical College, Department of Radiology, New York, NY (United States); Bander, Neil H. [Memorial Sloan Kettering Cancer Center, Department of Surgery, New York, NY (United States); Weill Cornell Medical College, Department of Urology, New York, NY (United States); Scher, Howard I.; Morris, Michael J. [Memorial Sloan Kettering Cancer Center, Department of Medicine, New York, NY (United States); Weill Cornell Medical College, Department of Medicine, New York, NY (United States)

    2014-11-15

    Given the bone tropism of prostate cancer, conventional imaging modalities poorly identify or quantify metastatic disease. {sup 89}Zr-huJ591 positron emission tomography (PET) imaging was performed in patients with metastatic prostate cancer to analyze and validate this as an imaging biomarker for metastatic disease. The purpose of this initial study was to assess safety, biodistribution, normal organ dosimetry, and optimal imaging time post-injection for lesion detection. Ten patients with metastatic prostate cancer received 5 mCi of {sup 89}Zr-huJ591. Four whole-body scans with multiple whole-body count rate measurements and serum activity concentration measurements were obtained in all patients. Biodistribution, clearance, and lesion uptake by {sup 89}Zr-huJ591 immuno-PET imaging was analyzed and dosimetry was estimated using MIRD techniques. Initial assessment of lesion targeting of {sup 89}Zr-huJ591 was done. Optimal time for imaging post-injection was determined. The dose was well tolerated with mild chills and rigors seen in two patients. The clearance of {sup 89}Zr-huJ591 from serum was bi-exponential with biological half-lives of 7 ± 4.5 h (range 1.1-14 h) and 62 ± 13 h (range 51-89 h) for initial rapid and later slow phase. Whole-body biological clearance was 219 ± 48 h (range 153-317 h). The mean whole-body and liver residence time was 78.7 and 25.6 h, respectively. Dosimetric estimates to critical organs included liver 7.7 ± 1.5 cGy/mCi, renal cortex 3.5 ± 0.4 cGy/mCi, and bone marrow 1.2 ± 0.2 cGy/mCi. Optimal time for patient imaging after injection was 7 ± 1 days. Lesion targeting of bone or soft tissue was seen in all patients. Biopsies were performed in 8 patients for a total 12 lesions, all of which were histologically confirmed as metastatic prostate cancer. One biopsy-proven lesion was not positive on {sup 89}Zr-huJ591, while the remaining 11 lesions were {sup 89}Zr-huJ591 positive. Two biopsy-positive nodal lesions were noted only on

  2. EORTC QLQ-BM22 and QLQ-C30 quality of life scores in patients with painful bone metastases of prostate cancer treated with strontium-89 radionuclide therapy

    International Nuclear Information System (INIS)

    Kurosaka, Shinji; Satoh, Takefumi; Chow, E.

    2012-01-01

    Approximately 80% of patients with prostate cancer will develop bone metastases, which often lead to bone pain and skeletal-related events. Sr-89 is an established alternative for the palliation of bone pain in prostate cancer. We aimed to assess the effect of Sr-89 radionuclide therapy on quality of life (QOL) in prostate cancer patients with painful bone metastases. Thirteen patients received a single intravenous injection of Sr-89 at a dose of 2.0 MBq/kg. All patients underwent QOL evaluation prior to Sr-89 treatment and 1, 2, and 3 months afterward using the Japanese version of the European Organisation for Research and Treatment of Cancer developed a Quality of Life questionnaire for Patients with Bone Metastases 22(EORTC QLQ-BM22), EORTC Quality of Life Group core questionnaire (EORTC QLQ-C30), a visual analog scale (VAS), and face scale. We also evaluated prostate-specific antigen (PSA) and serum alkaline phosphatase (ALP) response and toxicity of the Sr-89 therapy. The pain characteristics subscale of the EORTC QLQ-BM22 was significantly reduced from 1 month onward compared with the baseline. The functional interference and psychosocial aspects subscales were significantly higher than baseline from 2 months onward. At 2 months, VAS indicated a significant reduction in pain as compared to the baseline. Sr-89 therapy caused a nonsignificant reduction in PSA and ALP levels. No patients had leukocyte toxicity, and one patient had grade 3 platelet toxicity. Sr-89 radionuclide therapy can provide not only reduced pain characteristics but also better psychosocial aspects and functional interference in patients with painful bone metastases of prostate cancer. (author)

  3. HER2,TOP2A, and TIMP-1 and responsiveness to adjuvant anthracycline-containing chemotherapy in high-risk breast cancer patients

    DEFF Research Database (Denmark)

    Ejlertsen, Bent; Jensen, Maj-Britt; Nielsen, Kirsten V.

    2010-01-01

    analyzed individually. PATIENTS AND METHODS The Danish Breast Cancer Cooperative Group (DBCG) 89D trial randomly assigned 980 high-risk Danish breast cancer patients to CMF or CEF. Archival tumor tissue was analyzed TIMP-1, and HER2-negative and TIMP-1 immunoreactive tumors were classified as HT...... nonresponsive and otherwise HT responsive. Similarly, the 2T panel was constructed by combining TOP2A and TIMP-1; tumors with normal TOP2A status and TIMP-1 immunoreactivity were classified as 2T-nonresponsive and otherwise 2T-responsive. Results In total, 623 tumors were available for analysis, of which 154......(interaction) containing chemotherapy than HER2, TIMP-1, or TOP2A individually, and compared with these, 2T classifies a larger proportion of patients as sensitive to anthracyclines....

  4. miR-146a C/G polymorphism increased the risk of head and neck cancer, but overall cancer risk: an analysis of 89 studies.

    Science.gov (United States)

    Sun, Dezhong; Zhang, Xiaoyan; Zhang, Xiaolei

    2018-02-28

    Several studies have evaluated the association of miR-146a C/G with head and neck cancer (HNC) susceptibility, and overall cancer risk, but with inconclusive outcomes. To drive a more precise estimation, we carried out this meta-analysis. The literature was searched from MEDLINE (mainly PubMed), Embase, the Cochrane Library, and Google Scholar databases to identify eligible studies. A total of 89 studies were included. The results showed that miR-146a C/G was significantly associated with increased HNC risk in dominant model ( I 2 =15.6%, P heterogeneity =0.282, odds ratio (OR) =1.088, 95% confidence interval (CI) =1.002-1.182, P =0.044). However, no cancer risk was detected under all genetic models. By further stratified analysis, we found that rs4919510 mutation contributed to the risk of HNC amongst Asians under homozygote model ( I 2 =0, P heterogeneity =0.541, OR =1.189, 95% CI =1.025-1.378, P =0.022), and dominant model ( I 2 =0, P heterogeneity =0.959, OR =1.155, 95% CI =1.016-1.312, P =0.028). Simultaneously, in the stratified analysis by source of controls, a significantly increased cancer risk amongst population-based studies was found under homozygote model, dominant model, recessive model, and allele comparison model. However, no significant association was found in the stratified analysis by ethnicity and source of control. The results indicated that miR-146a C/G polymorphism may contribute to the increased HNC susceptibility and could be a promising target to forecast cancer risk for clinical practice. However, no significant association was found in subgroup analysis by ethnicity and source of control. To further confirm these results, well-designed large-scale case-control studies are needed in the future. © 2018 The Author(s).

  5. Long-term disease stabilization by strontium 89 (89Sr) for castration and docetaxel-resistant prostate cancer. A case report

    International Nuclear Information System (INIS)

    Kamiyama, Yuki; Iguchi, Ryo; Makino, Yuki; Kanamaru, Sojun; Ito, Noriyuki; Imanaka, Kazufumi

    2012-01-01

    A 67-year old man was diagnosed with advanced prostate cancer with multiple pelvic lymph nodes and multiple bone metastases (cT2N1M1b), with an initial prostate specific antigen of 1,300 ng/ml. Prostate biopsy specimens revealed poorly differentiated adenocarcinoma, Gleason's score 5+3. He was treated with maximal androgen blockade (MAB) from 2001, but showed resistance to hormone therapy and docetaxel in 2007. External radiation therapy for bone pain was difficult due to multiple lesions. 89 Sr therapy was started in 2009. The therapy could be performed 5 times without any side effects. Good pain control and decreasing prostate specific antigen (PSA) was obtained at each dose. (author)

  6. Control Information Based Microcontroller At89c51 Using Telephone Handheld

    OpenAIRE

    Agung Perdananto; Fivtatianti Fivtatianti. H, Skom, MM

    2007-01-01

    In writing that I make with the title "AT89C51 MICROCONTROLLER BASED CONTROL INFORMATION USING a mobile phone" is intended to be a system that can be used to control lighting with media that is already common cell phone and using AT89C51 microcontroller that can be developed further.

  7. Postmastectomy irradiation in high-risk breast cancer patients

    International Nuclear Information System (INIS)

    Overgaard, M.; Juul Christensen, J.; Johansen, H.; Nybo-Rasmussen, A.; Brincker, H.; Kooy, P. van der; Frederiksen, P.L.; Laursen, F.; Panduro, J.; Soerensen, N.E.; Gadeberg, C.C.; Hjelm-Hansen, M.; Overgaard, J.; West Andersen, K.; Zedeler, K.

    1988-01-01

    All pre- and postmenopausal high-risk breast cancer patients in the protocols DBCG 77 of the Danish Breast Cancer Cooperative Group received postmastectomy irradiation before randomization to either adjuvant systemic therapy or no such treatment. The actuarial loco-regional recurrence rate at 9 years was 6-17%, with the lowest rate in patients who also received additional adjuvant chemotherapy or tamoxifen. In a subsequent study (DBCG 82) the role of postmastectomy irradiation together with systemic treatment was evaluated in high-risk patients. Pre- and menopausal patients were randomized to postmastectomy irradiation+CMF (cyclophosphamide, methotrexate, 5-fluorouracil), CMF alone or CMF+TAM (tamoxifen). Postmenopausal patients were randomized to postmastectomy irradiation+TAM, TAM or CMF+TAM. At 4 years the loco-regional recurrence rate was significantly lower in the irradiated patients (5-7% vs. 23-33%). Further, disease-free survival was significantly improved in both pre- and postmenopausal irradiated patients compared with those who had only systemic treatment. At present, there are no significant differences between survival in the treatment groups. Thus, adjuvant systemic treatment alone (chemotherapy and/or tamoxifen) did not prevent loco-regional recurrences in high-risk patients after mastectomy and axillary lymph node sampling. However, a longer observation time is necessary to evaluate the consequence of primary optimal loco-regional tumour control in high-risk breast cancer patients with respect to survival. (orig.)

  8. Clinical observation of 89Sr treatment efficacy of multiple bone metastases in breast and prostate cancer patients

    International Nuclear Information System (INIS)

    Yuan Chao; Li Weipeng; Hu Yongquan; Tao Jian

    2010-01-01

    Objective: To evaluate the efficacy of 89 Sr in treatment of multiple bone metastases of breast and prostate cancer patients. Methods: Seventy multiple bone metastases patients (30 females with breast cancer and 40 males with prostate cancer) were treated with 89 Sr. The clinical effectiveness was assessed by Karnofsky performance score and whole body bone scanning data. Results: The total pain relief rate was 79% in bone metastases of breast cancer and 85% in bone metastases of prostate cancer, respectively. There was no significant differences between the two groups (χ 2 =0.78, P>0.05). The Karnofsky score was significantly improved in both groups (t=2.46, P 89 Sr treatment was good, and the quality of life was improved in patients with multiple bone metastases breast or prostate cancer. (authors)

  9. Strontium-89 for prostate cancer with bone metastases. The potential of cancer control and improvement of overall survival

    International Nuclear Information System (INIS)

    Kuroda, Isao

    2014-01-01

    Strontium-89 (Sr-89) has been considered to have a tumoricidal effect with minimal adverse events. However, few reports have investigated these effects in detail. In this study, we examined the tumoricidal and pain-relief effects of Sr-89 on prostate cancer with bone metastasis as well as survival. A retrospective study was performed involving 31 prostate cancer patients with bone metastasis treated with Sr-89. Using prostate specific antigen (PSA) as an evaluation criterion of cancer control, patients were divided into PSA responder and non-responder groups, and the survival rates of these groups were compared. In addition, using the total amount of painkillers administered as an evaluation criterion of pain relief, patients were divided into pain responder and non-responder groups, and the survival rates of these groups were also compared. As secondary investigation items, age, PSA (ng/ml), pain site, extent of the disease, the presence or absence of castration-resistant prostatic cancer (CRPC), the presence or absence of a past medical history of treatment with docetaxel in CRPC cases, Gleason Score, hemoglobin (g/dl), platelet (Plt) (/μl), serum carboxyterminal telopeptide of type I collagen (ng/ml), and bone-alkaline phosphatase (BAP) (U/l) were investigated. Longer survival was expected for the PSA responder group than for the PSA non-responder group, and whether the spine was the pain site and the presence or absence of CRPC were useful as predictors of this. Plt was suggested to be a useful indicator. Furthermore, the survival time was significantly longer in the pain responder group than in the pain non-responder group, and whether the pain site was present in the spine was considered to be a predictor; however, no significant difference was noted in any of the items assumed to be biomarkers. Sr-89 has the potential to control PSA and prolong survival. A large-scale prospective study of the therapeutic effect of Sr-89 is expected. (author)

  10. Localized prostate cancer in elderly men aged 80-89, findings from a population-based registry.

    Science.gov (United States)

    Vatandoust, S; Kichenadasse, G; O'Callaghan, M; Vincent, A D; Kopsaftis, T; Walsh, S; Borg, M; Karapetis, C S; Moretti, K

    2018-03-30

    To investigate the rate of death due to Prostate Cancer (PCa) and disease characteristics in patients diagnosed with Localized Prostate Cancer (LPCa) at age 80-89 years in comparison with men diagnosed at age 70-79. This is a retrospective study of data from the South Australian Prostate Cancer Clinical Outcomes Collaborative (SA-PCCOC). Included were men diagnosed between 2005 and 2014, aged ≥70 with no evidence of metastatic disease at presentation. Propensity score matching and competing risk Fine and Grey regression were used to assess the chance of treatment (curative v non-curative) and treatment effect on PCa specific-mortality. Of the 1951 eligible patients, 1428 (76%) aged 70-79, and 460 (24%) aged 80-89 yr at diagnosis (median age of 74 (IQR=72-76) and 83 (IQR=81-85) respectively). The 80-89 group had higher Gleason scores and PSA values (all pcopyright. All rights reserved. This article is protected by copyright. All rights reserved.

  11. PAM50 breast cancer intrinsic subtypes and effect of gemcitabine in advanced breast cancer patients

    DEFF Research Database (Denmark)

    Jørgensen, Charlotte Levin Tykjær; Nielsen, Torsten O; Bjerre, Karsten D

    2014-01-01

    BACKGROUND: In vitro studies suggest basal breast cancers are more sensitive to gemcitabine relative to other intrinsic subtypes. The main objective of this study was to use specimens from a randomized clinical trial to evaluate whether the basal-like subtype identifies patients with advanced...... breast cancer who benefit from gemcitabine plus docetaxel (GD) compared to single agent docetaxel (D). MATERIAL AND METHODS: From patients randomly assigned to GD or D, RNA was isolated from archival formalin-fixed, paraffin-embedded primary breast tumor tissue and used for PAM50 intrinsic subtyping...... chemotherapy were analyzed by the Kaplan-Meier method, and Cox proportional hazards regression models. Data analysis was performed independently by the Danish Breast Cancer Cooperative Group (DBCG) statistical core and all statistical tests were two-sided. RESULTS: RNA from 270 patients was evaluable; 84...

  12. Prototipe Rele Proteksi Overheating pada Motor 1 Phasa Berbasis Mikrokontroler AT89C51

    Directory of Open Access Journals (Sweden)

    Endi Permata

    2016-03-01

    Full Text Available Rele proteksi panas berlebih berbasis mikrokontroler AT89S51 merupakan suatu alat yang digunakan untuk memproteksi motor agar tidak terjadinya kerusakan pada motor. Pada penelitian ini dibuat prototipe rele proteksi panas berlebih pada motor 1 phasa berbasis mikrokontroler AT89S51 berdasarkan kelas isolator yang dipakai pada motor yaitu Y dan A dengan sistem pengendalinya adalah miukrokontroler AT89C51. Mikrokontroler AT89C51 sebagai pengendali dari piranti – piranti lain yang digunakan seperti sensor suhu LM35, Op-Amp, dan ADC, apabila suhu yang terdeteksi oleh sensor tidak sesuai dengan penyetingan batasnya tersebut maka mikrokontroler AT89C51 memerintahkan ke relay 12 Vdc untuk membunyikan alarm dan juga menghidupkan kontaktor yang terhubung ke motor. Sehingga Motor terselamatkan dari gangguan panas berlebih yang dapat menyebabkan motor terbakar. Adapun untuk mengetahui pada suhu berapa terjadinya gangguan pada motor ditampilkan melalui display LCD 16x2.

  13. Annotating MYC status with 89Zr-transferrin imaging.

    Science.gov (United States)

    Holland, Jason P; Evans, Michael J; Rice, Samuel L; Wongvipat, John; Sawyers, Charles L; Lewis, Jason S

    2012-10-01

    A noninvasive technology that quantitatively measures the activity of oncogenic signaling pathways could have a broad impact on cancer diagnosis and treatment with targeted therapies. Here we describe the development of (89)Zr-desferrioxamine-labeled transferrin ((89)Zr-transferrin), a new positron emission tomography (PET) radiotracer that binds the transferrin receptor 1 (TFRC, CD71) with high avidity. The use of (89)Zr-transferrin produces high-contrast PET images that quantitatively reflect treatment-induced changes in MYC-regulated TFRC expression in a MYC-driven prostate cancer xenograft model. Moreover, (89)Zr-transferrin imaging can detect the in situ development of prostate cancer in a transgenic MYC prostate cancer model, as well as in prostatic intraepithelial neoplasia (PIN) before histological or anatomic evidence of invasive cancer. These preclinical data establish (89)Zr-transferrin as a sensitive tool for noninvasive measurement of oncogene-driven TFRC expression in prostate and potentially other cancers, with prospective near-term clinical application.

  14. TAXTOX - a retrospective study regarding the side effects of docetaxel given as part of the adjuvant treatment to patients with primary breast cancer in Denmark from 2007 to 2009

    DEFF Research Database (Denmark)

    Eckhoff, Lise; Nielsen, Mette; Moeller, Susanne

    2011-01-01

    was given as three cycles of cyclophosphamide (600 mg/m(2)) and epirubicin (90 mg/m(2)) followed by three cycles of docetaxel (100 mg/m(2)). Because of an apparent high incidence of side effects, especially febrile neutropenia (FN) and non-hematologic side effects, the DBCG (The Danish Breast Cancer...

  15. Equity and improvement in outcome of breast cancer in Denmark

    DEFF Research Database (Denmark)

    Andreasen, A H; Mouridsen, H T; Andersen, K W

    1994-01-01

    The trend in the prognosis for female breast cancer patients was investigated by comparing Kaplan-Meier survival curves of different patient cohorts diagnosed during the period 1948-87. The study is based on 71,448 patients from the Danish Cancer Registry. The cohorts were defined by age...... in other parts of Denmark. For patients diagnosed in 1978-87 the prognosis, however, reached an equal level in all parts of the country. Thus, it is reasonable to assume that the national programme introduced in 1977 by the Danish Breast Cancer Cooperative Group (DBCG) has played an important role...... and not only brought about therapeutic improvements in breast cancer treatment in Denmark, but also ensured equity in the outcome on a national scale....

  16. Therapeutic effects of strontium-89 combined with endocrine therapy for treatment of bone metastasis in patients with prostate cancer

    International Nuclear Information System (INIS)

    Guo Deming

    2009-01-01

    Objective: To evaluate the effects of strontium-89 ( 89 Sr) combined with endocrine therapy for the treatment of bone metastasis in patients with advanced prostate cancer. Methods: 45 cases of prostate cancer with bone metastasis were randomly divided into 2 groups: patients in study group (23 cases) were given 89 Sr combined with endocrine therapy while patients in control group (22 cases) were given endocrine therapy only. The effect on pain relief, the serum PSA level, hemogram and biochemical indicators of hepatic and renal function were observed. Results: The pain degree was not statistically significant between two groups before treatment (P>0.05) and was statistically significant after treatment (P 89 Sr radionuclide combined with endocrine therapy was more effective than endocrine therapy alone in relief of the pain from bone metastasis and reduction of metastasis size in patients with advaced prostatic cancer. (authors)

  17. Clinical observation on strontium-89-chloride therapy in elder patients with prostate cancer for palliation of pain from bone metastases

    International Nuclear Information System (INIS)

    Chen Weimin; Lin Tiansheng; Wang Shen; Chen Tanying

    2006-01-01

    Objective: To estimate clinical curative efficacy and adverse reaction of 89 Sr-chloride therapy for palliation of pain from bone metastases in the older patients with prostate cancer. Methods: 48 cases of older patients with metastatic prostate cancer with bone pain were studied after androgen deprivation therapy, 89 Sr- chloride were administrated iv for the palliative treatment of metastatic bone pain. The curative effects in patients were investigated, including palliation of pain, change of metastatic focus, the tumor sign of PSA, and the adverse reaction. Results: After 89 Sr-chloride therapy, the total palliation rate was 89.6%, inefficiency rate was 10.4%, while metastatic focus and PSA decreased to some extent. No severe adverse reaction occurred. Conclusions: It is shown that the curative efficacy of acesodyne is evident after 89 Sr-chloride therapy in older patients suffering from bone metastase with prostate cancer. It is an effective therapeutic method for the palliation of pain from bone metastases especially to the older patients with multiple metastatases. (authors)

  18. Prediction of metastasis from low-malignant breast cancer by gene expression profiling

    DEFF Research Database (Denmark)

    Thomassen, Mads; Tan, Qihua; Eiriksdottir, Freyja

    2007-01-01

    examined in these studies is the low-risk patients for whom outcome is very difficult to predict with currently used methods. These patients do not receive adjuvant treatment according to the guidelines of the Danish Breast Cancer Cooperative Group (DBCG). In this study, 26 tumors from low-risk patients...... with different characteristics and risk, expression-based classification specifically developed in low-risk patients have higher predictive power in this group.......Promising results for prediction of outcome in breast cancer have been obtained by genome wide gene expression profiling. Some studies have suggested that an extensive overtreatment of breast cancer patients might be reduced by risk assessment with gene expression profiling. A patient group hardly...

  19. Multifocality as a prognostic factor in breast cancer patients registered in Danish Breast Cancer Cooperative Group (DBCG) 1996-2001

    DEFF Research Database (Denmark)

    Joergensen, L.E.; Gunnarsdottir, K.A.; Lanng, C.

    2008-01-01

    The purpose of this study was to investigate the prognostic influence of multifocality in breast cancer patients. In a cohort of 7196 patients there were 945 patients with multifocality. We found no prognostic influence of multifocality on overall survival when controlling for known prognostic......, Gunnarsdottir KA, Rasmussen BB, Moeller S, Lanng C. The prognostic influence of multifocality in breast cancer patients. Breast 2004;13:188-193]....... factors. We found a small but significant influence on disease-free survival (HR=1.16 [1.03-1.31]) and a strong correlation between multifocality and known prognostic factors. This was in accordance with an earlier study done on a smaller population and in a different period of time [Pedersen L...

  20. Annotating STEAP1 regulation in prostate cancer with 89Zr immuno-PET.

    Science.gov (United States)

    Doran, Michael G; Watson, Philip A; Cheal, Sarah M; Spratt, Daniel E; Wongvipat, John; Steckler, Jeffrey M; Carrasquillo, Jorge A; Evans, Michael J; Lewis, Jason S

    2014-12-01

    Antibodies and antibody-drug conjugates targeting the cell surface protein 6 transmembrane epithelial antigen of prostate 1 (STEAP1) are in early clinical development for the treatment of castration-resistant prostate cancer (PCa). In general, antigen expression directly affects the bioactivity of therapeutic antibodies, and the biologic regulation of STEAP1 is unusually complicated in PCa. Paradoxically, STEAP1 can be induced or repressed by the androgen receptor (AR) in different human PCa models, while also expressed in AR-null PCa. Consequently, there is an urgent need to translate diagnostic strategies to establish which regulatory mechanism predominates in patients to situate the appropriate therapy within standard of care therapies inhibiting AR. To this end, we prepared and evaluated (89)Zr-labeled MSTP2109A ((89)Zr-2109A), a radiotracer for PET derived from a fully humanized monoclonal antibody to STEAP1 in preclinical PCa models. (89)Zr-2109A specifically localized to the STEAP1-positive human PCa models CWR22Pc, 22Rv1, and PC3. Moreover, (89)Zr-2109A sensitively measured treatment-induced changes (∼66% decline) in STEAP1 expression in CWR22PC in vitro and in vivo, a model we showed to express STEAP1 in an AR-dependent manner. These findings highlight the ability of immuno-PET with (89)Zr-2109A to detect acute changes in STEAP1 expression and argue for an expansion of ongoing efforts to image PCa patients with (89)Zr-2109A to maximize the clinical benefit associated with antibodies or antibody-drug conjugates to STEAP1. © 2014 by the Society of Nuclear Medicine and Molecular Imaging, Inc.

  1. 89Zr-Cobalamin PET Tracer

    DEFF Research Database (Denmark)

    Kuda-Wedagedara, Akhila N W; Workinger, Jayme L; Nexo, Ebba

    2017-01-01

    Vitamin B12, or cobalamin (Cbl), is an essential nutrient. Acquisition, transport, and cellular internalization of Cbl are dependent on specific binding proteins and associated receptors. The circulating transport protein transcobalamin (TC) promotes cellular uptake via binding to specific......-Cbl (CN-Cbl). In vitro studies employing the CD320 receptor-positive breast cancer cell line MDA-MB-453 showed a 6- to 10-fold greater uptake of 89Zr-Cbl when compared with the uptake in the presence of 200-fold excess of CN-Cbl at 37 °C. We used nude mice with MDA-MB-453 tumors to study the feasibility...

  2. Selection of high risk groups among prognostically favorable patients with breast cancer.

    Science.gov (United States)

    Andersen, J A; Fischermann, K; Hou-Jensen, K; Henriksen, E; Andersen, K W; Johansen, H; Brincker, H; Mouridsen, H T; Castberg, T; Rossing, N; Rørth, M

    1981-01-01

    In a prospective, nationwide, decentralized breast cancer project conducted by The Danish Breast Cancer Cooperative Group (DBCG) the recurrence rate within the first year after surgery was analysed in relation to tumor anaplasia. One thousand forty-eight patients met the requirements of eligibility, i.e. tumor size less than or equal to 5 cm with negative axillary nodes, and no skin or deep invasion. The recurrence rates in tumors with anaplasia Grades I, II, and III were 4, 9, and 14%, respectively (p = 0.001). Therefore, it seems possible, prospectively, among otherwise prognostically favorable patients, to select a group with high risk of recurrence which might benefit from adjuvant systemic therapy. PMID:7247527

  3. Cyclophosphamide, methotrexate, and fluorouracil; oral cyclophosphamide; levamisole; or no adjuvant therapy for patients with high-risk, premenopausal breast cancer

    DEFF Research Database (Denmark)

    Ejlertsen, Bent Laursen; Mouridsen, Henning T; Jensen, Maj-Britt

    2010-01-01

    BACKGROUND: The Danish Breast Cancer Cooperative Group (DBCG) 77B trial examined the relative efficacy of levamisole, single-agent oral cyclophosphamide, and the classic combination of cyclophosphamide, methotrexate, and 5-fluorouracil (CMF) against no adjuvant systemic therapy in high-risk breast...... cancer patients. The authors report the results from that trial after a potential follow-up of 25 years. METHODS: Between 1977 and 1983, 1146 premenopausal patients who had tumors >5 cm or positive axillary lymph nodes were assigned randomly to 1 of 4 options: no systemic therapy, levamisole 5 mg weekly...... for 48 weeks (the levamisole arm), oral cyclophosphamide 130 mg/m(2) on Days 1 through 14 every 4 weeks for 12 cycles (the C arm), or oral cyclophosphamide 80 mg/m(2) on Days 1 through 14 plus methotrexate 30 mg/m(2) and fluorouracil 500 mg/m(2) intravenously on Days 1 and 8 every 4 weeks for 12 cycles...

  4. Vitamin C and survival among women with breast cancer: a meta-analysis.

    Science.gov (United States)

    Harris, Holly R; Orsini, Nicola; Wolk, Alicja

    2014-05-01

    The association between dietary vitamin C intake and breast cancer survival is inconsistent and few studies have specifically examined vitamin C supplement use among women with breast cancer. The purpose of this study was to summarise results from prospective studies on the association between vitamin C supplement use and dietary vitamin C intake and breast cancer-specific mortality and total mortality. Studies were identified using the PubMed database through February 6, 2014 and by examining the references of retrieved articles. Prospective studies were included if they reported relative risks (RR) with 95% confidence intervals (95% CIs) for at least two categories or as a continuous exposure. Random-effects models were used to combine study-specific results. The ten identified studies examined vitamin C supplement use (n=6) and dietary vitamin C intake (n=7) and included 17,696 breast cancer cases, 2791 total deaths, and 1558 breast cancer-specific deaths. The summary RR (95% CI) for post-diagnosis vitamin C supplement use was 0.81 (95% CI 0.72-0.91) for total mortality and 0.85 (95% CI 0.74-0.99) for breast cancer-specific mortality. The summary RR for a 100mg per day increase in dietary vitamin C intake was 0.73 (95% CI 0.59-0.89) for total mortality and 0.78 (95% CI 0.64-0.94) for breast cancer-specific mortality. Results from this meta-analysis suggest that post-diagnosis vitamin C supplement use may be associated with a reduced risk of mortality. Dietary vitamin C intake was also statistically significantly associated with a reduced risk of total mortality and breast cancer-specific mortality. Copyright © 2014 Elsevier Ltd. All rights reserved.

  5. Disseminated intravascular coagulation in a patient with metastatic prostate cancer: Fatal outcome following strontium-89 therapy

    Energy Technology Data Exchange (ETDEWEB)

    Leong, C.; McKenzie, R.; Coupland, D.B. [Univ. of British Columbia, (Canada)] [and others

    1994-10-01

    A patient with metastatic prostate cancer was found to have low-grade disseminated intravascular coagulation (DIC). He had significant bone pain despite external-beam radiotherapy and was given {sup 89}Sr with subsequent thrombocytopenia and epistaxis. The patient died from generalized hemorrhage 36 days postinjection. Although it is not possible to establish a causal relationship between {sup 89}Sr and DIC, practitioners should be alert to complications associated with the primary disorder which might occur at a time to raise concern about the intervention. 8 refs., 1 tab.

  6. Design of three-phased SPWM based on AT89C52

    Science.gov (United States)

    Wu, Xiaorui

    2018-05-01

    According to the AT89C52 and the area equivalent principle, a three phase SPWM algorithm based on the 8 bit single chip is obtained. Through computer programming, three-phase SPWM wave generated by a single chip microcomputer is applied to the circuit of the static reactive power generator. The result shows that this method is feasible and can reduce the cost of SVG.

  7. A comparison of the palliative effects of strontium-89 and external beam radiotherapy in metastatic prostate cancer

    International Nuclear Information System (INIS)

    Quilty, P.M.; Kirk, D.; Bolger, J.J.; Dearnaley, D.P.; Mason, M.D.; Lewington, V.J.; Reed, N.S.E.; Russell, J.M.; Yardley, J.

    1994-01-01

    From 1988 to 1991, 284 patients with prostatic cancer and painful bone metastases were treated with either radiotherapy or strontium-89 (200 MBq). Patients were first stratified according to suitability for local or hemibody radiotherapy, then randomly allocated that form of treatment or strontium-89 (i.v. injection). After 4,8 and 12 weeks pain sites were mapped, toxicity monitored, and all additional palliative treatments recorded. There was no significant difference in median survival (after >80% had died); 33 weeks following strontium 8 9 and 28 weeks following radiotherapy (p=0.1). All treatments provided effective pain relief; improvement was sustained to 3 months in 63.6% after hemibody radiotherapy compared with 66.1% after strontium-89, and in 61% after local radiotherapy compared with 65.9% in the comparable strontium 8 9 group. Fewer patients reported new pain sites after strontium-89 than after local or hemibody radiotherapy (p < 0.05). Radiotherapy to a new site was required by 12 patients in the local radiotherapy group compared with 2 after strontium-89 (p < 0.01), although there was no significant difference between hemibody radiotherapy (6 patients) and strontium-89 (9 patients) in this respect. Platelets and leukocytes fell by an average 30-40% after strontium-89 but sequelae were uncommon, and other symptoms rare

  8. Evaluation of (89Zr-labeled human anti-CD147 monoclonal antibody as a positron emission tomography probe in a mouse model of pancreatic cancer.

    Directory of Open Access Journals (Sweden)

    Aya Sugyo

    Full Text Available INTRODUCTION: Pancreatic cancer is an aggressive cancer and its prognosis remains poor. Therefore, additional effective therapy is required to augment and/or complement current therapy. CD147, high expression in pancreatic cancer, is involved in the metastatic process and is considered a good candidate for targeted therapy. CD147-specfic imaging could be useful for selection of appropriate patients. Therefore, we evaluated the potential of a fully human anti-CD147 monoclonal antibody 059-053 as a new positron emission tomography (PET probe for pancreatic cancer. METHODS: CD147 expression was evaluated in four pancreatic cancer cell lines (MIA Paca-2, PANC-1, BxPC-3, and AsPC-1 and a mouse cell line A4 as a negative control. Cell binding, competitive inhibition and internalization assays were conducted with (125I-, (67Ga-, or (89Zr-labeled 059-053. In vivo biodistribution of (125I- or (89Zr-labeled 059-053 was conducted in mice bearing MIA Paca-2 and A4 tumors. PET imaging with [(89Zr]059-053 was conducted in subcutaneous and orthotopic tumor mouse models. RESULTS: Among four pancreatic cancer cell lines, MIA Paca-2 cells showed the highest expression of CD147, while A4 cells had no expression. Immunohistochemical staining showed that MIA Paca-2 xenografts also highly expressed CD147 in vivo. Radiolabeled 059-053 specifically bound to MIA Paca-2 cells with high affinity, but not to A4. [(89Zr]059-053 uptake in MIA Paca-2 tumors increased with time from 11.0±1.3% injected dose per gram (ID/g at day 1 to 16.9±3.2% ID/g at day 6, while [(125I]059-053 uptake was relatively low and decreased with time, suggesting that 059-053 was internalized into tumor cells in vivo and (125I was released from the cells. PET with [(89Zr]059-053 clearly visualized subcutaneous and orthotopic tumors. CONCLUSION: [(89Zr]059-053 is a promising PET probe for imaging CD147 expression in pancreatic cancer and has the potential to select appropriate patients with CD147

  9. Clinical tests analysis; Analyses d'essai clinique

    Energy Technology Data Exchange (ETDEWEB)

    DeSilvio, M.; Valicenti, R.; Grignon, D.; O' Asbell, S.; Colleen Lawton, Ch.R.; Thomas, J.R.; William, S.; Abrious, S.; Lang, P.; Baujat, B.; Aufry, H.; Bourhis, J.; Chan, A.; Onat, H.; Chua, D.; Mazeron, R.; Gerard, J.P.; Conroy, T.; Bonnetain, F.; Bouche, O.; Chapet, O.; Closon-Dejardin, M.T.; Berges, O.; Bijker, N.; Meijnen, P.; Peterse, J.L.; Bogaerts, J.; Van Hoorebeeck, I.; Julien, J.P.; Ontkova, M.; Bosset, J.F.; Collette, L.; Calais, G.; Mineur, L.; Maingon, P.; Radosevic-Jelic, L.; Boostan, H.; Nielsen, H.M.; Overgaard, M.; Grau, C.; Jensen, A.R.; Overgaard, J.; Beneyton, V.; Noel, G

    2007-05-15

    The different subjects treated in this analysis are as follow: Whole-pelvis, 'mini-pelvis' or prostate only external beam radiotherapy after neo-adjuvant and concurrent hormonal therapy in patients treated in the radiation therapy oncology group 9413 trial; chemotherapy in locally advanced nasopharyngeal carcinoma: an individual patient data meta-analysis of eight randomized trials and 1753 patients; preoperative radiotherapy with or without concurrent fluorouracil and leucovorin in T3-4 rectal cancers: results of F.F.C.D. 9203; breast-conservative treatment with or without radiotherapy in ductal carcinoma-in-situ: ten year results of European Organisation for Research and Treatment of Cancer randomized phase III trial 1085. A study by the E.O.R.T.C. Breast Cancer Cooperative Group and E.O.R.T.C. Radiotherapy Group; chemotherapy with preoperative radiotherapy in rectal cancer; locoregional recurrence after mastectomy in high-risk breast cancer-risk and prognosis. An analysis of patients from the D.B.C.G. 82 b and c randomization trials. (N.C.)

  10. Repeated 89Sr therapy in breast cancer patient with multiple bone metastases

    International Nuclear Information System (INIS)

    Lee, Jae Soung; Yang, Weon Il; Kim, Byung Il; Choi, Chang Woon; Lim, Sang Moo; Hong, Soung Woon

    2000-01-01

    The single 89 Sr therapy has been used for pain relief in patients with multiple bony metastases and it is known to be very effective without serious complications except mild bone marrow suppression. But usually repeated therapy is needed because it is not a completely curative therapy. This study was performed to evaluate the effects of repeated 89 Sr therapy on therapeutic outcome compared to first therapy. This study was performed retrospectively with fifteen breast cancer patients treated more than twice with 89 SrCl 2 against multiple bony metastases. There were total 42 cases-there were eight, four, two and one patients treated twice, three times, four times and six times respectively. The time interval between therapy was 179.1±107.5 (90-550) days. We scored zero to five about performance, analgesics, subjective pain, sleep pattern respectively and summed as the pain score (0-20). Before therapy and one month and three months after therapy the pain score was evaluated and blood leukocyte and platelet was estimated. Bone scan was performed before therapy and one, three and six months after therapy. The pain score was 6.5±2.4 (2-10) before first therapy. Among 42 cases the pain score was improved in 22 cases (52.4%), not changed in 8 cases (19.0%) and aggravated in 12 cases (28.6%). The pain score was not affected by therapy number. Bone scan showed various changes without statistical correlation with pain score. One month after therapy blood leukocyte and platelet was decreased more than 20% than before therapy in six cases (28.6%) and seven cases (16.7%) among 21 cases, respectively. The leukocyte and platelet was not more decreased as increased therapy number. The repeated 89 Sr therapy is not so different from the first therapy in effects and bone marrow suppression. Bone scan finding was independent to the pain score

  11. Design and construction of AT89C2051 micro controller based water level indicator for poly tank manufacturers

    International Nuclear Information System (INIS)

    Ashong, Cynthia Ama

    2011-08-01

    This project is aimed at designing and constructing an AT89C2051 Micro controller Based Water level Indicator by programming a micro controller that has high frequency, logic, clock circuitry and 2.7V to 6V operating range with 5V volts being logic level 1 and 0 Volts being logic level 0 using Assembler language and programming the AT89C2051 Microcontroller using Galep 4 programmer. The device component and assembly includes A T89C2051 Micro controller, sensor (copper probe), bread board, electric bell for alarm to indicate low water level and a bulb to indicate high water level (that is the water tank is full). The AT89C2051 Micro controller Based Water Level Indicator works by sounding a bell when the tank is empty or the water level is low and light a bulb when the poly tank is full. The boundary within which the device operates is at the upper water level and the lower water level of the device (tank). That is it can operate within the levels of high to low limit. The result is very useful since it will help in ensuring water security. It is satisfactory since the project is working and indicating that the water level is low or high (that is the tank is empty or full). (au)

  12. Relationship between the prognostic and predictive value of the intrinsic subtypes and a validated gene profile predictive of loco-regional control and benefit from post-mastectomy radiotherapy in patients with high-risk breast cancer

    DEFF Research Database (Denmark)

    Tramm, Trine; Kyndi, Marianne; Myhre, Simen

    2014-01-01

    , and has shown prognostic impact in terms of loco-regional failure and predictive impact for PMRT. Reports have also shown predictive value in terms of benefit of PMRT from intrinsic subtypes and derived approximations. The aim of this study was to examine: 1) the agreement between various methods...... for determining the intrinsic subtypes; and 2) the relationship between the prognostic and predictive impact of the DBCG-RT profile and the intrinsic subtypes. MATERIAL AND METHODS: Intrinsic subtypes and the DBCG-RT profile was determined from microarray analysis based on fresh frozen tissue from 191 patients...... and predictive information obtained from the DBCG-RT profile cannot be substituted by any approximation of the tumors intrinsic subtype. The predictive value of the intrinsic subtypes in terms of PMRT was influenced by the method used for assignment to the intrinsic subtypes....

  13. Male breast cancer: a nation-wide population-based comparison with female breast cancer.

    Science.gov (United States)

    Lautrup, Marianne D; Thorup, Signe S; Jensen, Vibeke; Bokmand, Susanne; Haugaard, Karen; Hoejris, Inger; Jylling, Anne-Marie B; Joernsgaard, Hjoerdis; Lelkaitis, Giedrius; Oldenburg, Mette H; Qvamme, Gro M; Soee, Katrine; Christiansen, Peer

    2018-05-01

    Describe prognostic parameters of Danish male breast cancer patients (MBCP) diagnosed from 1980-2009. Determine all-cause mortality compared to the general male population and analyze survival/mortality compared with Danish female breast cancer patients (FBCP) in the same period. The MBCP cohort was defined from three national registers. Data was extracted from medical journals. Data for FBCP is from the DBCG database. Overall survival (OS) was quantified by Kaplan-Meier estimates. Standardized mortality ratios (SMRs) were calculated based on mortality rate among patients relative to the mortality rate in the general population. The association between SMR and risk factors were analyzed in univariate and multivariable Poisson regression models. Separate models for each gender were used for the analyses. We found a marked difference in OS for the two genders. For the total population of MBCP, 5- and 10-year survivals were 55.1% and 31.7%, respectively. For FBCP, the corresponding figures were 76.8% and 59.3%. Median age at diagnosis for FBCP was 61 years and 70 years for MBCP. By applying SMR, the difference in mortality between genders equalized and showed pronounced age-dependency. For males <40 years, SMR was 9.43 and for females 19.56 compared to SMR for males 80 + years (0.95) and females 80 + years (0.89). During the period 1980-2009, the risk of dying gradually decreased for FBCP (p < .0001). The risk 1980-1984 was 35% higher than 2005-2009 (RR 1.35). Although the risk of dying for MBCP was also lowest in 2005-2009, there was no clear tendency (p = .1439). The risk was highest in 1990-1994 (RR =2.48). We found better OS for FBCP than for MBCP. But SMR showed similar mortality rate for the two genders, except for very young FBCP, who had higher SMR. Furthermore, significantly improved survival over time for FBCP was observed, with no clear tendency for MBCP.

  14. 10 CFR 1040.89-6 - Mediation.

    Science.gov (United States)

    2010-01-01

    ... 10 Energy 4 2010-01-01 2010-01-01 false Mediation. 1040.89-6 Section 1040.89-6 Energy DEPARTMENT... Enforcement Procedures § 1040.89-6 Mediation. (a) Referral of complaints for mediation. DOE will refer to the Federal Mediation and Conciliation Service, in accordance with 45 CFR 90.43(c)(3), all complaints that: (1...

  15. Prognostic significance of axillary dissection in breast cancer patients with micrometastases or isolated tumor cells in sentinel nodes

    DEFF Research Database (Denmark)

    Tvedskov, Tove Filtenborg; Jensen, Maj-Britt; Ejlertsen, Bent

    2015-01-01

    We estimated the impact of axillary lymph node dissection (ALND) on the risk of axillary recurrence (AR) and overall survival (OS) in breast cancer patients with micrometastases or isolated tumor cells (ITC) in sentinel nodes. We used the Danish Breast Cancer Cooperative Group (DBCG) database...... to identify patients with micrometastases or ITC in sentinel nodes following surgery for primary breast cancer between 2002 and 2008. A Cox proportional hazard regression model was developed to assess the hazard ratios (HR) for AR and OS between patients with and without ALND. We identified 2074 patients...... and 2.21 (95 % CI 0.54-8.95, P = 0.27), in patients with ITC after a median follow-up of 6 years and 3 months. There was no significant difference in overall survival between patients with and without ALND, when adjusting for age, co-morbidity, tumor size, histology type, malignancy grade...

  16. Hepatitis C virus infection and risk of cancer: a population-based cohort study

    Directory of Open Access Journals (Sweden)

    Lars Haukali Omland

    2010-06-01

    Full Text Available Lars Haukali Omland1, Dora Körmendiné Farkas2, Peter Jepsen2,3, Niels Obel1, Lars Pedersen21Department of Infectious Diseases, Rigshospitalet, Denmark; 2Department of Clinical Epidemiology, 3Department of Medicine V (Hepatology and Gastroenterology, Aarhus University Hospital, DenmarkBackground: Hepatitis C virus (HCV infection is associated with an increased risk of primary liver cancer; however, 5- and 10-year risk estimates are needed. The association of HCV with non-Hodgkin lymphoma (NHL is uncertain and the association with other cancers is unknown.Method: We conducted a nationwide, population-based cohort study of 4,349 HCV-infected patients in Denmark, computing standardized incidence ratios (SIR of cancer incidence in HCV infected patients compared with cancer incidence of the general population. We calculated 5-and 10-year risks of developing cancer, stratifying our analyses based on the presence of HIV coinfection and cirrhosis.Results: We recorded an increased risk of primary liver cancer (SIR: 76.63 [95% CI: 51.69–109.40], NHL (SIR: 1.89 [95% CI: 0.39–5.52], and several smoking- and alcohol-related cancers in HCV infected patients without HIV coinfection. HCV-infected patients without HIV coinfection had a 6.3% (95% CI: 4.6%–8.7% risk of developing cancer and 2.0% (95% CI: 1.1%–3.8% risk of developing primary liver cancer within 10 years.Conclusion: We confirmed the association of HCV infection with primary liver cancer and NHL. We also observed an association between HCV infection and alcohol- and smoking-related cancers.Keywords: hepatitis C virus, non-Hodgkin lymphoma, standardized incidence ratio, cancer

  17. Evaluation of and quality assurance in HER2 analysis in breast carcinomas from patients registered in Danish Breast Cancer Group (DBCG) in the period of 2002-2006. A nationwide study including correlation between HER-2 status and other prognostic variables.

    Science.gov (United States)

    Rasmussen, Birgitte Bruun; Andersson, Michael; Christensen, Ib J; Møller, Susanne

    2008-01-01

    In Denmark, analysis for HER2 is situated in the pathology laboratories dealing with breast pathology. The analysis was introduced during the late 1990's, and was gradually intensified in the following years up to now. The present study deals with the experience with the analysis during the last 5 years, from 2002 - 2006. All patients, registered in DBCG (Danish Breast Cancer Group) and with a HER2-test were included. The analysis followed international recommendations, with an initial immunohistochemical (IHC) analysis with a semiquantitative grading of the reaction in four grades, 0 and 1+, defined as HER2-negative, 2+, equivocal and 3+, HER2-positive. In the 2+ group, a FISH-test was applied to identify the presence of gene amplification, defined as a ratio >/=2. We investigated the number of analyses performed, the number of positive cases and the relation between the result of IHC and the result of FISH. Furthermore we looked at the relation to other prognostic factors. The number of analyses gradually increased during the years of investigation, from 30% of patients in 2002 to 71% in 2006. The increase was seen in all laboratories resulting in all laboratories but one having a substantial number of analyses. Sixty-two percent of all cases were HER2-negative, 18% were equivocal and 21% positive in the IHC-analysis. Of the 2+, equivocal cases, 23% had gene-amplification. Thus, 23% of patients were defined as HER2-positive and eligible for treatment with trastuzumab. There was a significant correlation to other prognostic factors. The results are in accordance with what is found elsewhere. The quality of the test is further assured by all laboratories participating in external quality assurance schemes.

  18. Downregulated CDKN1C/p57kip2 drives tumorigenesis and associates with poor overall survival in breast cancer.

    Science.gov (United States)

    Qiu, Zhu; Li, Yunhai; Zeng, Beilei; Guan, Xiaoqin; Li, Hongzhong

    2018-02-26

    CDKN1C, also known as p57 kip2 , is considered to be a potential tumor suppressor implicated in several kinds of human cancers. However, the current knowledge of CDKN1C in breast cancer remains obscure. In the present study, we demonstrated that CDKN1C was dramatically downregulated in breast cancer compared with normal tissues by using real-time quantitative polymerase chain reaction, western blot and two public data portals: The Cancer Genome Atlas (TCGA) and Oncomine datasets. Moreover, the expression of CDKN1C was correlated with age and tumor size in the TCGA cohort containing 708 cases of breast cancer. Low expression of CDKN1C was significantly associated with poor overall survival (OS) in the TCGA cohort and validated cohort composed of 1402 patients. Multivariate Cox regression analysis indicated that CDKN1C was an independent prognostic factor for worse OS (HR = 1.78, 95% CI: 1.09-2.89, p = 0.020). Furthermore, gene set enrichment analysis (GSEA) revealed that CDKN1C was significantly correlated with gene signatures involving DNA repair, cell cycle, glycolysis, adipogenesis, and two critical signaling pathways mTORC1 and PI3K/Akt/mTOR. In conclusion, our data suggested an essential role of CDKN1C in the tumorgenesis of breast cancer. Targeting CDKN1C may be a promising strategy for anticancer therapeutics. Copyright © 2018 Elsevier Inc. All rights reserved.

  19. Second primary cancers after adjuvant radiotherapy in early breast cancer patients: A national population based study under the Danish Breast Cancer Cooperative Group (DBCG)

    International Nuclear Information System (INIS)

    Grantzau, Trine; Mellemkjær, Lene; Overgaard, Jens

    2013-01-01

    Background and purpose: To analyze the long-term risk of second primary solid non-breast cancer in a national population-based cohort of 46,176 patients treated for early breast cancer between 1982 and 2007. Patients and methods: All patients studied were treated according to the national guidelines of the Danish Breast Cancer Cooperative Group. The risk of second primary cancers was estimated by Standardised incidence ratios (SIRs) and multivariate Cox regression models were used to estimate adjusted hazard ratios (HR) among irradiated women compared to non-irradiated. All irradiated patients were treated on linear accelerators. Second cancers were a priori categorized into two groups; radiotherapy-associated- (oesophagus, lung, heart/mediastinum, pleura, bones, and connective tissue) and non-radiotherapy-associated sites (all other cancers). Results: 2358 second cancers had occurred during the follow-up. For the radiotherapy-associated sites the HR among irradiated women was 1.34 (95% CI 1.11–1.61) with significantly increased HRs for the time periods of 10–14 years (HR 1.55; 95% CI 1.08–2.24) and ⩾15 years after treatment (HR 1.79; 95% CI 1.14–2.81). There was no increased risk for the non-radiotherapy-associated sites (HR 1.04; 95% CI 0.94–1.1). The estimated attributable risk related to radiotherapy for the radiotherapy-associated sites translates into one radiation-induced second cancer in every 200 women treated with radiotherapy. Conclusions: Radiotherapy treated breast cancer patients have a small but significantly excess risk of second cancers

  20. Organized nation-wide implementation of sentinel lymph node biopsy in Denmark

    DEFF Research Database (Denmark)

    Friis, E.; Galatius, H.; Garne, J.P.

    2008-01-01

    they could include patients into the study. As a result of this strategy the sentinel lymph node staging was fully implemented in all Danish surgical breast cancer centres within three years and all sentinel node biopsies in the period were recorded in the DBCG data centre. Furthermore, the strategy...

  1. Hilar and mediastinal lymph node metastases from lung cancer

    International Nuclear Information System (INIS)

    Koganemaru, Michihiko; Fujimoto, Kiminori; Nishimura, Hiroshi; Tabuchi, Akinori; Ohtake, Hisashi; Nishimura, Yutaka

    1990-01-01

    Sixty-one patients with primary lung cancer, who had CT and MR imaging before surgery, were studied. MR imaging used spin-echo sequences with T1 weighted image and T2 weighted image (C-MRI), and included STIR technique (Stir-MRI). The accuracy of diagnosis of mediastinal lymphadenopathy (regarding 10 mm or larger in short transverse diameter as positive) was 89% by CT, 84% by C-MRI and 89% by Stir-MRI. The accuracy of diagnosis of hilar lymphadenopathy was 42% by CT, 67% by C-MRI, and 75% by Stir-MRI. The accuracy of diagnosis of mediastinal lymph node metastases was 89% by CT, 94% by C-MRI and 96% by Stir-MRI. The accuracy of diagnosis of hilar lymph node metastases was 78% by CT, 87% by C-MRI and 89% by Stir-MRI. The possibility of enhancement of diagnostic accuracy of lymph node metastases from lung cancer was suggested by combining MR imaging including STIR technique, with CT. (author)

  2. Different fatty acid metabolism effects of (−-Epigallocatechin-3-Gallate and C75 in Adenocarcinoma lung cancer

    Directory of Open Access Journals (Sweden)

    Relat Joana

    2012-07-01

    Full Text Available Abstract Background Fatty acid synthase (FASN is overexpressed and hyperactivated in several human carcinomas, including lung cancer. We characterize and compare the anti-cancer effects of the FASN inhibitors C75 and (−-epigallocatechin-3-gallate (EGCG in a lung cancer model. Methods We evaluated in vitro the effects of C75 and EGCG on fatty acid metabolism (FASN and CPT enzymes, cellular proliferation, apoptosis and cell signaling (EGFR, ERK1/2, AKT and mTOR in human A549 lung carcinoma cells. In vivo, we evaluated their anti-tumour activity and their effect on body weight in a mice model of human adenocarcinoma xenograft. Results C75 and EGCG had comparable effects in blocking FASN activity (96,9% and 89,3% of inhibition, respectively. In contrast, EGCG had either no significant effect in CPT activity, the rate-limiting enzyme of fatty acid β-oxidation, while C75 stimulated CPT up to 130%. Treating lung cancer cells with EGCG or C75 induced apoptosis and affected EGFR-signaling. While EGCG abolished p-EGFR, p-AKT, p-ERK1/2 and p-mTOR, C75 was less active in decreasing the levels of EGFR and p-AKT. In vivo, EGCG and C75 blocked the growth of lung cancer xenografts but C75 treatment, not EGCG, caused a marked animal weight loss. Conclusions In lung cancer, inhibition of FASN using EGCG can be achieved without parallel stimulation of fatty acid oxidation and this effect is related mainly to EGFR signaling pathway. EGCG reduce the growth of adenocarcinoma human lung cancer xenografts without inducing body weight loss. Taken together, EGCG may be a candidate for future pre-clinical development.

  3. Strontium-89 in palliative treatment of widespread painful bone metastases: Response rate and duration

    International Nuclear Information System (INIS)

    Haddad, Peiman; Ghadiri, Farhad

    2005-01-01

    Full text: Intravenous injection of Strontium-89 (Sr-89) is an accepted palliative treatment for bone metastases. We evaluated the pain relief achieved with this radiopharmaceutical in patients with widespread painful bone metastases from prostate and breast cancers. Pain intensity on a 9-grade scale and use of narcotics was recorded before and after Sr-89 injection, and the ensuing palliative effect was divided into complete, partial and no response. The duration of response was also recorded. Thirty-five patients with widespread painful bone metastases were treated with Sr-89, of whom 22 had prostate and 13 breast cancers. Mean follow-up was 227 days, during which death was recorded for 32 patients. Fourteen patients (40%) had a complete response, 9 (26%) partial and 12 (34%) no response. In the 23 responding patients, mean duration of response was 6 months. In 17 patients the response was present until death. There was no significant relationship between pain response and patients' age or type of primary cancer. No side effects were recorded other than mild and temporary drop in white blood cell and platelet counts. Three patients with a complete response had a second injection of Sr-89 after progression of pain. One of these patients had a second partial response; the other 2 did not show a response to the second injection. The use of Sr-89 for treatment of widespread painful bone metastases from prostate and breast cancers in our department showed a 66% rate of response and a mean response duration of 6 months, with no significant side effects. (author)

  4. Combined gold seed implantation and external radiotherapy for stage B2 or C prostate cancer

    International Nuclear Information System (INIS)

    Carey, P.O.; Lippert, M.C.; Constable, W.C.; Jones, D.; Talton, B.M.

    1988-01-01

    Patients with clinical stage B2 or C prostatic carcinoma represent a group for which there are several treatment options. We followed the course and outcome of 72 patients with clinical stages B and C prostate cancer who were treated with surgical staging, insertion of gold grains and external radiation at our institutions between 1975 and 1984. Of the patients 44 (61 per cent) had clinical stage B disease and the majority (89 per cent) of these were stage B2 lesions. The remaining 28 patients (39 per cent) had clinical stage C tumors. In our series 27 per cent of the clinical stage B and 68 per cent of the clinical stage C cancer patients had positive lymph nodes. The 5-year survival free of disease was 52 per cent for patients with both stages of disease. The 7-year survival free of disease was 47 per cent for patients with clinical stage B and 14 per cent for those with clinical stage C cancer. Lymph node status did not have a statistically significant effect on total survival but survival free of disease correlated significantly with node status. Local treatment failures were defined as patients who required transurethral prostatic resection or orchiectomy for palliation of obstructive symptoms related to local tumor regrowth. By these criteria we prevented local progression in 78 per cent of the patients at 5 years

  5. Preparation of 14C-labeled 8,9-didehydro-6,8-dimethyl-2-methylthioergoline mesylate, a dopamine antagonist potentially useful in the treatment of schizophrenia

    International Nuclear Information System (INIS)

    Wheeler, W.J.

    1988-01-01

    We have prepared 14 C-labeled 8,9-didehydro-6,8-dimethyl-2-methyl-thioergoline mesylate (LY 170542), a dopamine antagonist potentially useful as an anti-psychotic. The 14 C-label was introduced via a novel application of the Wittig reaction on 1-(4'-toluene-sulfonyl)-8,9-didehydro-6-methyl-ergolin-8-one and subsequent reduction of 1-(4'-toluenesulfonyl)-17-[ 14 C]-lysergene by lithium/ammonia at -33 0 C. The 17-[ 14 C]-agroclavine thus prepared was converted into 17-[ 14 C]-LY 170542 by reaction with methanesulfenyl chloride/methanesulfonic acid. (author)

  6. Similar substrate specificity of cynomolgus monkey cytochrome P450 2C19 to reported human P450 2C counterpart enzymes by evaluation of 89 drug clearances.

    Science.gov (United States)

    Hosaka, Shinya; Murayama, Norie; Satsukawa, Masahiro; Uehara, Shotaro; Shimizu, Makiko; Iwasaki, Kazuhide; Iwano, Shunsuke; Uno, Yasuhiro; Yamazaki, Hiroshi

    2015-12-01

    Cynomolgus monkeys are used widely in preclinical studies as non-human primate species. The amino acid sequence of cynomolgus monkey cytochrome P450 (P450 or CYP) 2C19 is reportedly highly correlated to that of human CYP2C19 (92%) and CYP2C9 (93%). In the present study, 89 commercially available compounds were screened to find potential substrates for cynomolgus monkey CYP2C19. Of 89 drugs, 34 were metabolically depleted by cynomolgus monkey CYP2C19 with relatively high rates. Among them, 30 compounds have been reported as substrates or inhibitors of, either or both, human CYP2C19 and CYP2C9. Several compounds, including loratadine, showed high selectivity to cynomolgus monkey CYP2C19, and all of these have been reported as human CYP2C19 and/or CYP2C9 substrates. In addition, cynomolgus monkey CYP2C19 formed the same loratadine metabolite as human CYP2C19, descarboethoxyloratadine. These results suggest that cynomolgus monkey CYP2C19 is generally similar to human CYP2C19 and CYP2C9 in its substrate recognition functionality. Copyright © 2015 John Wiley & Sons, Ltd.

  7. Molecular subtyping of breast cancer improves identification of both high and low risk patients

    DEFF Research Database (Denmark)

    Rossing, Maria; Østrup, Olga; Majewski, Wiktor W.

    2018-01-01

    classification and final reports were available prior to the multidisciplinary conference. Using a prognostic standard mortality rate index (PSMRi) developed by the Danish Breast Cancer Group (DBCG) 39 patients were assigned with an intermediate risk and among these 16 (41%) were furthermore diagnosed...... by the multi-gene signature assigned with a luminal A tumor and consequently spared adjuvant chemotherapy. There was overall agreement between mRNA derived and IHC hormone receptor status, whereas IHC Ki67 protein proliferative index proved inaccurate, compared to the mRNA derived index. Forty-one patients...... with basal-like (basL) subtypes were screened for predisposing mutations regardless of clinical predisposition. Of those 17% carried pathogenic mutations. Conclusion: Transcriptome based subtyping of breast tumors evidently reduces the need for adjuvant chemotherapy and improves identification of women...

  8. Health-related quality of life in early breast cancer.

    Science.gov (United States)

    Groenvold, Mogens

    2010-09-01

    The treatment of primary breast cancer usually consists of surgery often followed by adjuvant therapy (radiotherapy, chemotherapy, hormonal treatment, etc.) to reduce the risk of recurrence. The cancer diagnosis and the treatments may have significant impact on the patients' quality of life. This thesis deals with scientific aspects and clinical results of a study aimed at assessing the impact of breast cancer (and its treatment) on the patients' quality of life. Studies such as this assessing the problems and symptoms experienced by the patients are often referred to as health-related quality of life (HRQL) research. HRQL research deals with subjective experiences and raises challenging, scientific questions. Therefore, much attention was directed towards methodological issues in this clinically motivated project. The study was a prospective, longitudinal, questionnaire-based investigation of women with newly diagnosed breast cancer registered in the Danish Breast Cancer Co-operative Group's DBCG 89 Program. The patients were sub-divided into low-risk and high-risk patients. High-risk patients were offered randomisation in one of three randomised adjuvant therapy trials involving chemotherapy, ovarian ablation, and endocrine therapy. After a literature study and interviews with breast cancer patients, a questionnaire was composed that included two widely used standard questionnaires (EORTC QLQ-C30 and Hospital Anxiety and Depression (HAD) Scale) and a DBCG 89 Questionnaire developed for this study. A total of 1,898 eligible patients were invited by post to participate in the study involving six assessments over a 2-year period, and 1,713 patients (90%) completed the first questionnaire. Furthermore, a questionnaire was sent to 872 women selected at random from the general population; 608 (70%) responded. The multi-item scales of the two standard questionnaires were analysed for so-called differential item functioning (DIF) in order to investigate whether the

  9. EURALERT-89 user's guide

    International Nuclear Information System (INIS)

    Mueller, H.; Friedland, W.; Proehl, G.; Paretzke, H.G.

    1990-09-01

    EURALERT-89 is a dose assessment program system including countermeasures which has been developed in the framework of the C.E.C. research programme 'Radiological aspects of nuclear accident scenarios'. For this purpose the ECOSYS model for calculating the transfer of radionuclides through the environment, the contamination of foodstuffs and potential doses has been adapted to real-time use in the different European countries. In this user's guide the file names are given in the form SUBD/FNAM; this means that the data file with name FNAM is in the subdirectory SUBD. Remember that writing the path of a file depends on the computer used. With EURALERT-89 it is relatively simple to get an estimate of the most important informations (deposition, maximum specific activities in foodstuffs, most important dose values) for all locations which are included in the input file. This goal can be achieved with only a few commands. (orig./HP)

  10. 26 CFR 5c.168(f)(8)-9 - Pass-through leases-transfer of only the investment tax credit to a party other than the ultimate...

    Science.gov (United States)

    2010-04-01

    ... investment tax credit to a party other than the ultimate user of the property. [Reserved] 5c.168(f)(8)-9...) INCOME TAX (CONTINUED) TEMPORARY INCOME TAX REGULATIONS UNDER THE ECONOMIC RECOVERY TAX ACT OF 1981 § 5c.168(f)(8)-9 Pass-through leases—transfer of only the investment tax credit to a party other than the...

  11. Study of Λ+c production and Pentaquark search in WA89 CERN experiment data

    International Nuclear Information System (INIS)

    Charignon, F.

    1995-01-01

    This thesis is dedicated to the study of the Λ c + charmed baryon and to the ''Pentaquark'' search, within the framework of the CERN WA89 experiment. This fixed target experiment is using a 330 GeV/c hyperon beam. Its aim is the production and the study of baryons carrying charm and strangeness as well as the search of multiquarks. The experimental setup is built around the CERN Omega spectrometer. Production and decay vertices of charmed particles are reconstructed by means of microstrip detectors. Multiwire proportional chambers reconstruct the trajectories in the Omega magnetic field and particle identification is provided by a Ring Imaging Cherenkov detector. An invariant mass signal has been obtained for the Λ c + in the proton-kaon-pion decay channel. Distorsion effects occurring in the event reconstruction have been taken into account in the estimation of the Λ c + lifetime and production cross-section. Finally, the exotic multiquark state ''Pentaquark'' was investigated in the channel proton-phi-pion but no signal was observed. (author). 86 refs., 56 figs

  12. High-dose vitamin C and cancer

    Directory of Open Access Journals (Sweden)

    Ahmet Unlu, M.D.

    2016-01-01

    Full Text Available Vitamin C (ascorbic acid, ascorbate is a basic compound that is of great importance with its role in various enzymatic reactions including the synthesis of collagen, as well as with its redox functions. Vitamin C has become the center of interest in cancer studies, in consequence of the facts that connective tissue changes and vitamin C deficiency were first alleged to be associated with cancer in the 1950s; and that high doses of vitamin C was asserted to be cytotoxic for cancer cells, later on. The results of the first study carried out in the 1970s were promising; but afterwards, the studies were ascertained to be faulty. Despite the positive results achieved from some laboratory and animal experiments, randomized clinical trials did not verify those findings, and no clear benefit of vitamin C for cancer treatment could be demonstrated. As for studies, where its use in combination with other cancer treatment regimens was assessed, conflicting results were obtained. Although intake of high doses of vitamin C is alleged to be harmless, based on that it is in the group of water soluble vitamins and is not stored in the body, there are many side effects and drug interactions reported in the literature. For now, it is better to abstain from this treatment, until the benefit of the treatment (if any is clearly demonstrated, considering the potential side effects and interactions.

  13. Association Studies of HFE C282Y and H63D Variants with Oral Cancer Risk and Iron Homeostasis Among Whites and Blacks

    Directory of Open Access Journals (Sweden)

    Nathan R. Jones

    2015-12-01

    Full Text Available Background: Polymorphisms in the hemochromatosis (HFE gene are associated with excessive iron absorption from the diet, and pro-oxidant effects of iron accumulation are thought to be a risk factor for several types of cancer. Methods: The C282Y (rs1800562 and H63D (rs1799945 polymorphisms were genotyped in 301 oral cancer cases and 437 controls and analyzed in relation to oral cancer risk, and serum iron biomarker levels from a subset of 130 subjects. Results: Individuals with the C282Y allele had lower total iron binding capacity (TIBC (321.2 ± 37.2 µg/dL vs. 397.7 ± 89.0 µg/dL, p = 0.007 and higher percent transferrin saturation (22.0 ± 8.7 vs. 35.6 ± 22.9, p = 0.023 than wild type individuals. Iron and ferritin levels approached significantly higher levels for the C282Y allele (p = 0.0632 and p = 0.0588, respectively. Conclusions: Iron biomarker levels were elevated by the C282Y allele, but neither (rs1800562 nor (rs1799945 was associated with oral cancer risk in blacks and whites.

  14. Vitamin C supplement intake and postmenopausal breast cancer risk: interaction with dietary vitamin C.

    Science.gov (United States)

    Cadeau, Claire; Fournier, Agnès; Mesrine, Sylvie; Clavel-Chapelon, Françoise; Fagherazzi, Guy; Boutron-Ruault, Marie-Christine

    2016-07-01

    Experimental and epidemiologic studies have yielded conflicting results on the relation between vitamin C intake and breast cancer risk. We investigated the relation between vitamin C supplement intake and breast cancer risk while considering dietary vitamin C intake. Between 1995 and 2008, 2482 invasive breast cancer cases occurred in 57,403 postmenopausal women from the Etude Epidémiologique auprès de femmes de la Mutuelle Générale de l'Education Nationale (E3N) prospective cohort during 581,085 person-years. We estimated vitamin C intake from foods with the use of a validated food-frequency questionnaire that was sent to subjects in 1993-1995 and vitamin C supplement use via questionnaires sent in 1995, 2000, 2002, and 2005. Multivariable HRs (95% CIs) for primary invasive breast cancer were estimated with the use of Cox regression models. All statistical tests were 2-sided. Vitamin C supplement use (ever compared with never) was not associated with breast cancer risk overall; it was associated with higher breast cancer risk in women in the fourth quartile of vitamin C intake from foods (HR: 1.32; 95% CI: 1.04, 1.67) but not in other quartiles of dietary vitamin C intake (P-interaction = 0.03). We observed that vitamin C supplement use was associated with increased postmenopausal breast cancer risk in women with high vitamin C intake from foods. Our data suggest a potential U- or J-shaped relation between total vitamin C intake and postmenopausal breast cancer risk that deserves further investigation. © 2016 American Society for Nutrition.

  15. APC/C Dysfunction Limits Excessive Cancer Chromosomal Instability.

    Science.gov (United States)

    Sansregret, Laurent; Patterson, James O; Dewhurst, Sally; López-García, Carlos; Koch, André; McGranahan, Nicholas; Chao, William Chong Hang; Barry, David J; Rowan, Andrew; Instrell, Rachael; Horswell, Stuart; Way, Michael; Howell, Michael; Singleton, Martin R; Medema, René H; Nurse, Paul; Petronczki, Mark; Swanton, Charles

    2017-02-01

    Intercellular heterogeneity, exacerbated by chromosomal instability (CIN), fosters tumor heterogeneity and drug resistance. However, extreme CIN correlates with improved cancer outcome, suggesting that karyotypic diversity required to adapt to selection pressures might be balanced in tumors against the risk of excessive instability. Here, we used a functional genomics screen, genome editing, and pharmacologic approaches to identify CIN-survival factors in diploid cells. We find partial anaphase-promoting complex/cyclosome (APC/C) dysfunction lengthens mitosis, suppresses pharmacologically induced chromosome segregation errors, and reduces naturally occurring lagging chromosomes in cancer cell lines or following tetraploidization. APC/C impairment caused adaptation to MPS1 inhibitors, revealing a likely resistance mechanism to therapies targeting the spindle assembly checkpoint. Finally, CRISPR-mediated introduction of cancer somatic mutations in the APC/C subunit cancer driver gene CDC27 reduces chromosome segregation errors, whereas reversal of an APC/C subunit nonsense mutation increases CIN. Subtle variations in mitotic duration, determined by APC/C activity, influence the extent of CIN, allowing cancer cells to dynamically optimize fitness during tumor evolution. We report a mechanism whereby cancers balance the evolutionary advantages associated with CIN against the fitness costs caused by excessive genome instability, providing insight into the consequence of CDC27 APC/C subunit driver mutations in cancer. Lengthening of mitosis through APC/C modulation may be a common mechanism of resistance to cancer therapeutics that increase chromosome segregation errors. Cancer Discov; 7(2); 218-33. ©2017 AACR.See related commentary by Burkard and Weaver, p. 134This article is highlighted in the In This Issue feature, p. 115. ©2017 American Association for Cancer Research.

  16. The pig as a model for therapeutic human anti-cancer vaccine development, elucidating the T-cell reactivity against IDO and RhoC

    DEFF Research Database (Denmark)

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

    is important. Previous development of therapeutic cancer vaccines has largely been based on studies in mice and the majority of these candidate vaccines failed to establish therapeutic responses in subsequent human clinical trials. Since the porcine immunome is more closely related to the human counterpart, we...... here introduce pigs as a superior large animal model for human cancer vaccine development via the use of our unique technology for swine leukocyte antigen (SLA) production. IDO and RhoC, both known to be important in human cancer development and progression, were used as vaccine targets. Pigs were......, and peptide-SLA complex stability measurements revealed 89 stable (t½ ≥ 0.5 hour) complexes. Vaccine-induced peptide-specific CTL responses were monitored using IFN-γ release as a read out. We found responses to IDO- and RhoC-derived peptides across all groups; surprisingly non-stably binding peptides also...

  17. Neoadjuvant letrozole for postmenopausal estrogen receptor-positive, HER2-negative breast cancer patients, a study from the Danish Breast Cancer Cooperative Group (DBCG)

    DEFF Research Database (Denmark)

    Skriver, Signe Korsgaard; Laenkholm, Anne-Vibeke; Rasmussen, Birgitte Bruun

    2018-01-01

    response and 55% of patients had partial pathological response. ER at 100%, ductal subtype, tumor size below 2 cm and lymph node-negative status was significantly associated with a better response to NET and malignancy grade 3 with a poorer response to NET. One patient progressed during treatment......INTRODUCTION: Neoadjuvant endocrine treatment (NET) is a low-toxicity approach to achieve operability in locally advanced breast cancer, and to facilitate breast conservation in early breast cancer, particular in patients with highly estrogen receptor (ER) positive and HER2-negative disease. Here......, we report the results obtained by neoadjuvant letrozole in patients with early breast cancer in a phase-II design. MATERIAL AND METHODS: A total of 119 postmenopausal women with ER-positive, HER2-negative operable breast cancer were assigned to four months of neoadjuvant letrozole before definitive...

  18. Elevated c-Src and c-Yes expression in malignant skin cancers

    Directory of Open Access Journals (Sweden)

    Lee Jang

    2010-08-01

    Full Text Available Abstracts Background Src family kinases (SFKs play an important role in cancer proliferation, survival, motility, invasiveness, metastasis, and angiogenesis. Among the SFKs, c-Src and c-Yes are particularly over-expressed or hyper-activated in many human epithelial cancers. However, only a few studies have attempted to define the expression and role of c-Src and c-Yes in cutaneous carcinomas. Objectives To investigate the expression of c-Src and c-Yes in cutaneous carcinomas to include malignant melanoma (MM, squamous cell carcinoma (SCC and basal cell carcinoma (BCC. Methods We examined 6 normal skin tissues and 18 malignant skin tumor tissues using western blotting for the expression of c-Src and c-Yes. In another set, 16 specimens of MM, 16 SCCs and 16 BCCs were analyzed for the expression of c-Src and c-Yes using immunohistochemical staining. Results Western blotting showed that c-Src was expressed in all malignant skin tumors, but not in normal skin, while c-Yes was expressed in MM and SCC, but not in BCC and normal skin. Immunohistochemical staining results of c-Src and c-Yes in MM, SCC, and BCC mirrored those of the western blot analysis. Conclusions c-Src, rather than c-Yes, plays a key role in the proliferation and progression of malignant skin cancers.

  19. {sup 89}Zr-labeled nivolumab for imaging of T-cell infiltration in a humanized murine model of lung cancer

    Energy Technology Data Exchange (ETDEWEB)

    England, Christopher G.; Ehlerding, Emily B.; Ellison, Paul A.; Hernandez, Reinier; Barnhart, Todd E. [University of Wisconsin - Madison, Department of Medical Physics, Madison, WI (United States); Jiang, Dawei [Health Science Center, Shenzhen University, Guangdong Key Laboratory for Biomedical Measurements and Ultrasound Imaging, School of Biomedical Engineering, Guangzhou (China); University of Wisconsin - Madison, Department of Radiology, Madison, WI (United States); Rekoske, Brian T. [University of Wisconsin - Madison, Department of Medicine, Madison, WI (United States); McNeel, Douglas G. [University of Wisconsin - Madison, Department of Medicine, Madison, WI (United States); University of Wisconsin Carbone Cancer Center, Madison, WI (United States); Huang, Peng [Health Science Center, Shenzhen University, Guangdong Key Laboratory for Biomedical Measurements and Ultrasound Imaging, School of Biomedical Engineering, Guangzhou (China); Cai, Weibo [University of Wisconsin - Madison, Department of Medical Physics, Madison, WI (United States); University of Wisconsin - Madison, Department of Radiology, Madison, WI (United States); University of Wisconsin Carbone Cancer Center, Madison, WI (United States)

    2018-01-15

    Nivolumab is a human monoclonal antibody specific for programmed cell death-1 (PD-1), a negative regulator of T-cell activation and response. Acting as an immune checkpoint inhibitor, nivolumab binds to PD-1 expressed on the surface of many immune cells and prevents ligation by its natural ligands. Nivolumab is only effective in a subset of patients, and there is limited evidence supporting its use for diagnostic, monitoring, or stratification purposes. {sup 89}Zr-Df-nivolumab was synthesized to map the biodistribution of PD-1-expressing tumor infiltrating T-cells in vivo using a humanized murine model of lung cancer. The tracer was developed by radiolabeling the antibody with the positron emitter zirconium-89 ({sup 89}Zr). Imaging results were validated by ex vivo biodistribution studies, and PD-1 expression was validated by immunohistochemistry. Data obtained from PET imaging were used to determine human dosimetry estimations. The tracer showed elevated binding to stimulated PD-1 expressing T-cells in vitro and in vivo. PET imaging of {sup 89}Zr-Df-nivolumab allowed for clear delineation of subcutaneous tumors through targeting of localized activated T-cells expressing PD-1 in the tumors and salivary glands of humanized A549 tumor-bearing mice. In addition to tumor uptake, salivary and lacrimal gland infiltration of T-cells was noticeably visible and confirmed via histological analysis. These data support our claim that PD-1-targeted agents allow for tumor imaging in vivo, which may assist in the design and development of new immunotherapies. In the future, noninvasive imaging of immunotherapy biomarkers may assist in disease diagnostics, disease monitoring, and patient stratification. (orig.)

  20. Lactobacillus salivarius strain FDB89 induced longevity in Caenorhabditis elegans by dietary restriction.

    Science.gov (United States)

    Zhao, Yang; Zhao, Liang; Zheng, Xiaonan; Fu, Tianjiao; Guo, Huiyuan; Ren, Fazheng

    2013-04-01

    In this study, we utilized the nematode Caenorhabditis elegans to assess potential life-expanding effect of Lactobacillus salivarius strain FDB89 (FDB89) isolated from feces of centenarians in Bama County (Guangxi, China). This study showed that feeding FDB89 extended the mean life span in C. elegans by up to 11.9% compared to that of control nematodes. The reduced reproductive capacities, pharyngeal pumping rate, growth, and increased superoxide dismutase (SOD) activity and XTT reduction capacity were also observed in FDB89 feeding worms. To probe the anti-aging mechanism further, we incorporated a food gradient feeding assay and assayed the life span of eat-2 mutant. The results demonstrated that the maximal life span of C. elegans fed on FDB89 was achieved at the concentration of 1.0 mg bacterial cells/plate, which was 10-fold greater than that of C. elegans fed on E. coli OP50 (0.1 mg bacterial cells/plate). However, feeding FDB89 could not further extend the life span of eat-2 mutant. These results indicated that FDB89 modulated the longevity of C. elegans in a dietary restriction-dependent manner and expanded the understanding of anti-aging effect of probiotics.

  1. The cAMP-dependent protein kinase inhibitor H-89 attenuates the bioluminescence signal produced by Renilla Luciferase.

    Directory of Open Access Journals (Sweden)

    Katie J Herbst

    2009-05-01

    Full Text Available Investigations into the regulation and functional roles of kinases such as cAMP-dependent protein kinase (PKA increasingly rely on cellular assays. Currently, there are a number of bioluminescence-based assays, for example reporter gene assays, that allow the study of the regulation, activity, and functional effects of PKA in the cellular context. Additionally there are continuing efforts to engineer improved biosensors that are capable of detecting real-time PKA signaling dynamics in cells. These cell-based assays are often utilized to test the involvement of PKA-dependent processes by using H-89, a reversible competitive inhibitor of PKA.We present here data to show that H-89, in addition to being a competitive PKA inhibitor, attenuates the bioluminescence signal produced by Renilla luciferase (RLuc variants in a population of cells and also in single cells. Using 10 microM of luciferase substrate and 10 microM H-89, we observed that the signal from RLuc and RLuc8, an eight-point mutation variant of RLuc, in cells was reduced to 50% (+/-15% and 54% (+/-14% of controls exposed to the vehicle alone, respectively. In vitro, we showed that H-89 decreased the RLuc8 bioluminescence signal but did not compete with coelenterazine-h for the RLuc8 active site, and also did not affect the activity of Firefly luciferase. By contrast, another competitive inhibitor of PKA, KT5720, did not affect the activity of RLuc8.The identification and characterization of the adverse effect of H-89 on RLuc signal will help deconvolute data previously generated from RLuc-based assays looking at the functional effects of PKA signaling. In addition, for the current application and future development of bioluminscence assays, KT5720 is identified as a more suitable PKA inhibitor to be used in conjunction with RLuc-based assays. These principal findings also provide an important lesson to fully consider all of the potential effects of experimental conditions on a cell

  2. Association between H-RAS T81C genetic polymorphism and gastrointestinal cancer risk: A population based case-control study in China

    Directory of Open Access Journals (Sweden)

    Li Qilong

    2008-09-01

    Full Text Available Abstract Background Gastrointestinal cancer, such as gastric, colon and rectal cancer, is a major medical and economic burden worldwide. However, the exact mechanism of gastrointestinal cancer development still remains unclear. RAS genes have been elucidated as major participants in the development and progression of a series of human tumours and the single nucleotide polymorphism at H-RAS cDNA position 81 was demonstrated to contribute to the risks of bladder, oral and thyroid carcinoma. Therefore, we hypothesized that this polymorphisms in H-RAS could influence susceptibility to gastrointestinal cancer as well, and we conducted this study to test the hypothesis in Chinese population. Methods A population based case-control study, including 296 cases with gastrointestinal cancer and 448 healthy controls selected from a Chinese population was conducted. H-RAS T81C polymorphism was genotyped by Polymerase Chain Reaction-Restriction Fragment Length Polymorphism (PCR-RFLP assay. Results In the healthy controls, the TT, TC and CC genotypes frequencies of H-RAS T81C polymorphism, were 79.24%, 19.87% and 0.89%, respectively, and the C allele frequency was 10.83%. Compared with TT genotype, the TC genotype was significantly associated with an increased risk of gastric cancer (adjusted OR = 3.67, 95%CI = 2.21–6.08, while the CC genotype showed an increased risk as well (adjusted OR = 3.29, 95%CI = 0.54–19.86, but it was not statistically significant. In contrast, the frequency of TC genotype was not significantly increased in colon cancer and rectal cancer patients. Further analysis was performed by combining TC and CC genotypes compared against TT genotype. As a result, a statistically significant risk with adjusted OR of 3.65 (95%CI, 2.22–6.00 was found in gastric cancer, while no significant association of H-RAS T81C polymorphism with colon cancer and rectal cancer was observed. Conclusion These findings indicate, for the first time, that there

  3. Association between H-RAS T81C genetic polymorphism and gastrointestinal cancer risk: A population based case-control study in China

    International Nuclear Information System (INIS)

    Zhang, Yongjing; Jin, Mingjuan; Liu, Bing; Ma, Xinyuan; Yao, Kaiyan; Li, Qilong; Chen, Kun

    2008-01-01

    Gastrointestinal cancer, such as gastric, colon and rectal cancer, is a major medical and economic burden worldwide. However, the exact mechanism of gastrointestinal cancer development still remains unclear. RAS genes have been elucidated as major participants in the development and progression of a series of human tumours and the single nucleotide polymorphism at H-RAS cDNA position 81 was demonstrated to contribute to the risks of bladder, oral and thyroid carcinoma. Therefore, we hypothesized that this polymorphisms in H-RAS could influence susceptibility to gastrointestinal cancer as well, and we conducted this study to test the hypothesis in Chinese population. A population based case-control study, including 296 cases with gastrointestinal cancer and 448 healthy controls selected from a Chinese population was conducted. H-RAS T81C polymorphism was genotyped by Polymerase Chain Reaction-Restriction Fragment Length Polymorphism (PCR-RFLP) assay. In the healthy controls, the TT, TC and CC genotypes frequencies of H-RAS T81C polymorphism, were 79.24%, 19.87% and 0.89%, respectively, and the C allele frequency was 10.83%. Compared with TT genotype, the TC genotype was significantly associated with an increased risk of gastric cancer (adjusted OR = 3.67, 95%CI = 2.21–6.08), while the CC genotype showed an increased risk as well (adjusted OR = 3.29, 95%CI = 0.54–19.86), but it was not statistically significant. In contrast, the frequency of TC genotype was not significantly increased in colon cancer and rectal cancer patients. Further analysis was performed by combining TC and CC genotypes compared against TT genotype. As a result, a statistically significant risk with adjusted OR of 3.65 (95%CI, 2.22–6.00) was found in gastric cancer, while no significant association of H-RAS T81C polymorphism with colon cancer and rectal cancer was observed. These findings indicate, for the first time, that there is an H-RAS T81C polymorphism existing in Chinese population

  4. Efficacy of c-Met inhibitor for advanced prostate cancer

    International Nuclear Information System (INIS)

    Tu, William H; Zhu, Chunfang; Clark, Curtis; Christensen, James G; Sun, Zijie

    2010-01-01

    Aberrant expression of HGF/SF and its receptor, c-Met, often correlates with advanced prostate cancer. Our previous study showed that expression of c-Met in prostate cancer cells was increased after attenuation of androgen receptor (AR) signalling. This suggested that current androgen ablation therapy for prostate cancer activates c-Met expression and may contribute to development of more aggressive, castration resistant prostate cancer (CRPC). Therefore, we directly assessed the efficacy of c-Met inhibition during androgen ablation on the growth and progression of prostate cancer. We tested two c-Met small molecule inhibitors, PHA-665752 and PF-2341066, for anti-proliferative activity by MTS assay and cell proliferation assay on human prostate cancer cell lines with different levels of androgen sensitivity. We also used renal subcapsular and castrated orthotopic xenograft mouse models to assess the effect of the inhibitors on prostate tumor formation and progression. We demonstrated a dose-dependent inhibitory effect of PHA-665752 and PF-2341066 on the proliferation of human prostate cancer cells and the phosphorylation of c-Met. The effect on cell proliferation was stronger in androgen insensitive cells. The c-Met inhibitor, PF-2341066, significantly reduced growth of prostate tumor cells in the renal subcapsular mouse model and the castrated orthotopic mouse model. The effect on cell proliferation was greater following castration. The c-Met inhibitors demonstrated anti-proliferative efficacy when combined with androgen ablation therapy for advanced prostate cancer

  5. Mechanistic studies on β-ketoacyl thiolase from Zoogloea ramigera: Identification of the active-site nucleophile as Cys89, its mutation to Ser89, and kinetic and thermodynamic characterization of wild-type and mutant enzymes

    International Nuclear Information System (INIS)

    Thompson, S.; Mayerl, F.; Walsh, C.T.; Peoples, O.P.; Masamune, S.; Sinskey, A.J.

    1989-01-01

    Thiolase proceeds via covalent catalysis involving an acetyl-S-enzyme. The active-site thiol nucleophile is identified as Cys 89 by acetylation with [ 14 C]acetyl-CoA, rapid denaturation, tryptic digestion, and sequencing of the labeled peptide. The native acetyl enzyme is labile to hydrolytic decomposition with t 1/2 of 2 min at pH 7, 25 degree C. Cys 89 has been converted to the alternate nucleophile Ser 89 by mutagenesis and the C89S enzyme overproduced, purified, and assessed for activity. The Ser 89 enzyme retains 1% of the V max of the Cys 89 enzyme in the direction of acetoacetyl-CoA thiolytic cleavage and 0.05% of the V max in the condensation of two acetyl-CoA molecules. A covalent acetyl-O-enzyme intermediate is detected on incubation with [ 14 C]acetyl-CoA and isolation of the labeled Ser 89 -containing tryptic peptide. Comparisons of the Cys 89 and Ser 89 enzymes have been made for kinetic and thermodynamic stability of the acetyl enzyme intermediates both by isolation and by analysis of [ 32 P]CoASH/acetyl-CoA partial reactions and for rate-limiting steps in catalysis with trideuterioacetyl-CoA

  6. CHEK2 c.1100delC allele is rarely identified in Greek breast cancer cases.

    Science.gov (United States)

    Apostolou, Paraskevi; Fostira, Florentia; Papamentzelopoulou, Myrto; Michelli, Maria; Panopoulos, Christos; Fountzilas, George; Konstantopoulou, Irene; Voutsinas, Gerassimos E; Yannoukakos, Drakoulis

    2015-04-01

    The CHEK2 gene encodes a protein kinase that plays a crucial role in maintenance of genomic integrity and the DNA repair mechanism. CHEK2 germline mutations are associated with increased risk of breast cancer and other malignancies. From a clinical perspective, the most significant mutation identified is the c.1100delC mutation, which is associated with an approximately 25% lifetime breast cancer risk. The distribution of this mutation shows wide geographical variation; it is more prevalent in the Northern European countries and less common, or even absent, in Southern Europe. In order to estimate the frequency of the CHEK2 c.1100delC mutation in Greek breast cancer patients, we genotyped 2,449 patients (2,408 females and 41 males), which was the largest series ever tested for c.1100delC. The mean age of female and male breast cancer diagnosis was 49 and 59 years, respectively. All patients had previously tested negative for the Greek BRCA1 founder and recurrent mutations. The CHEK2 c.1100delC mutation was detected in 0.16% (4 of 2,408) of females, all of whom were diagnosed with breast cancer before the age of 50 years. Only one c.1100delC carrier was reported with breast cancer family history. The present study indicates that the CHEK2 c.1100delC mutation does not contribute substantially to hereditary breast cancer in patients of Greek descent. Copyright © 2015 Elsevier Inc. All rights reserved.

  7. Identification of copy number variations and translocations in cancer cells from Hi-C data.

    Science.gov (United States)

    Chakraborty, Abhijit; Ay, Ferhat

    2017-10-18

    with CNV events for a breast cancer cell line (r=0.89) and capture most of the CNVs we simulate using Avesim. For HiCtrans predictions, we report evidence from the literature for 30 out of 90 translocations for eight of our cancer cell lines. Furthermore, we show that our tools identify and correctly classify relatively understudied rearrangements such as double minutes (DMs) and homogeneously staining regions (HSRs). Considering the inherent limitations of existing techniques for karyotyping (i.e., missing balanced rearrangements and those near repetitive regions), the accurate identification of CNVs and translocations in a cost-effective and high-throughput setting is still a challenge. Our results show that the set of tools we develop effectively utilize moderately sequenced Hi-C libraries (100-300 million reads) to identify known and de novo chromosomal rearrangements/abnormalities in well-established cancer cell lines. With the decrease in required number of cells and the increase in attainable resolution, we believe that our framework will pave the way towards comprehensive mapping of genomic rearrangements in primary cells from cancer patients using Hi-C. CNV calling: https://github.com/ay-lab/HiCnvTranslocation calling: https://github.com/ay-lab/HiCtransHi-C simulation: https://github.com/ay-lab/AveSim. © The Author (2017). Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com

  8. C-C motif ligand 5 promotes migration of prostate cancer cells in the prostate cancer bone metastasis microenvironment.

    Science.gov (United States)

    Urata, Satoko; Izumi, Kouji; Hiratsuka, Kaoru; Maolake, Aerken; Natsagdorj, Ariunbold; Shigehara, Kazuyoshi; Iwamoto, Hiroaki; Kadomoto, Suguru; Makino, Tomoyuki; Naito, Renato; Kadono, Yoshifumi; Lin, Wen-Jye; Wufuer, Guzailinuer; Narimoto, Kazutaka; Mizokami, Atsushi

    2018-03-01

    Chemokines and their receptors have key roles in cancer progression. The present study investigated chemokine activity in the prostate cancer bone metastasis microenvironment. Growth and migration of human prostate cancer cells were assayed in cocultures with bone stromal cells. The migration of LNCaP cells significantly increased when co-cultured with bone stromal cells isolated from prostate cancer bone metastases. Cytokine array analysis of conditioned medium from bone stromal cell cultures identified CCL5 as a concentration-dependent promoter of LNCaP cell migration. The migration of LNCaP cells was suppressed when C-C motif ligand 5 (CCL5) neutralizing antibody was added to cocultures with bone stromal cells. Knockdown of androgen receptor with small interfering RNA increased the migration of LNCaP cells compared with control cells, and CCL5 did not promote the migration of androgen receptor knockdown LNCaP. Elevated CCL5 secretion in bone stromal cells from metastatic lesions induced prostate cancer cell migration by a mechanism consistent with CCL5 activity upstream of androgen receptor signaling. © 2017 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.

  9. Validity, reliability and understanding of the EORTC-C30 and EORTC-BR23, quality of life questionnaires specific for breast cancer

    Directory of Open Access Journals (Sweden)

    Fernanda Alessandra Silva Michels

    2013-06-01

    Full Text Available Objective: To validate and assess reliability and understanding of the EORTC–C30 quality of life questionnaire and its breast cancer specific module, the EORTC-BR23. Methods: This study was conducted at the AC Camargo Cancer Hospital, São Paulo, Brazil. A total of 100 women diagnosed with breast cancer were interviewed. Internal consistency, confirmatory factorial analysis, convergent validity, construct validity and degree of understanding were examined. Reliability was assessed by comparison of means at times 1 and 2, inter-class coefficient and Bland-Altman graphics. Results: Cronbach’s alpha ranged from 0.72 to 0.86 for the EORTC-C30 and from 0.78 to 0.83 for the EORTC-BR23 questionnaire. Most questions were confirmed in the confirmatory factorial analysis. In the construct validity analysis, the questionnaires were capable of differentiating patients with or without lymphedema, apart from the symptom scales of both questionnaires. Both questionnaires presented a significant correlation in most domains of the SF-36, in the convergent validity analysis. Only a few criticisms were reported concerning questions, and the mean grade of understanding was high (C30 = 4.91 and BR23 = 4.89. The questionnaires presented good rates of reliability, with the exception of the functional scale of the C30 and the symptom scale of the BR23. Conclusions: The EORTC-C30 and EORTC-BR23 quality of life questionnaires were validated, presented good rates of reliability and are easily understood, allowing them to be used in Brazil to assess quality of life among women with breast cancer.

  10. The analyzing power Asub(y)[(theta) for 12C(n,nsub(0,1))12C betwen 8.9 and] 14.9 MeV neutron energy

    International Nuclear Information System (INIS)

    Woye, E.; Tornow, W.; Mack, G.; Clegg, T.B.; Wylie, W.

    1983-01-01

    The analyzing power Asub(#betta#)(theta) for 12 C(n,n) 12 C elastic scattering and for inelastic scattering to the first excited state (Jsup(π) = 2 + , Q = -4.44 MeV) of 12 C was measured in the energy range from 8.9 to 14.9 MeV in 1 MeV steps. A pulsed polarized neutron beam was produced via the 2 H(d vector,n vector) 3 He polarization transfer reaction. Monte Carlo simulations were used to correct the data for finite geometry and multiple scattering effects. The Asub(#betta#) data, together with publsihed cross-section data, were analyzed in the framework of the spherical optical model and in the coupled-channels formalism. A good description of the data has been achieved. (orig.)

  11. RhoC a new target for therapeutic vaccination against metastatic cancer

    DEFF Research Database (Denmark)

    Wenandy, L.; Sorensen, R.B.; Straten, P.T.

    2008-01-01

    Most cancer deaths are due to the development of metastases. Increased expression of RhoC is linked to enhanced metastatic potential in multiple cancers. Consequently, the RhoC protein is an attractive target for drug design. The clinical application of immunotherapy against cancer is rapidly...... of cancer makes RhoC a very attractive target for anti-cancer immunotherapy. Herein, we describe an HLA-A3 restricted epitope from RhoC, which is recognized by cytotoxic T cells. Moreover, RhoC-specific T cells show cytotoxic potential against HLA-matched cancer cells of different origin. Thus, RhoC may...... moving forward in multiple areas, including the adoptive transfer of anti-tumor-reactive T cells and the use of "therapeutic" vaccines. The over-expression of RhoC in cancer and the fact that immune escape by down regulation or loss of expression of this protein would reduce the morbidity and mortality...

  12. Health-related quality of life after adjuvant and salvage postoperative radiotherapy for prostate cancer - A prospective analysis

    International Nuclear Information System (INIS)

    Pinkawa, Michael; Fischedick, Karin; Asadpour, Branka; Gagel, Bernd; Piroth, Marc D.; Holy, Richard; Krenkel, Barbara; Eble, Michael J.

    2008-01-01

    Background and purpose: The aim of the study was to analyze health-related quality of life changes after postoperative radiotherapy (RT) for prostate cancer. Materials and methods: A group of 101 patients has been surveyed prospectively before (time A), at the last day (B), two months after (C) and >1 year after (D) RT using a validated questionnaire (Expanded Prostate Cancer Index Composite) with urinary, bowel, sexual and hormonal domains. The prostatic fossa was treated with a four-field box technique up to a total dose of 66.6 Gy. Results: While median urinary scores reached baseline levels already two months after radiotherapy (function/bother scores at time A-B-C-D: 94/89-89/75-94/89-94/89; A vs. B: p 1 year, only minor HRQOL changes occurred in comparison to baseline scores

  13. Post-mastectomy radiotherapy in Denmark: From 2D to 3D treatment planning guidelines of The Danish Breast Cancer Cooperative Group

    DEFF Research Database (Denmark)

    Thomsen, Mette Skovhus; Berg, Martin; Nielsen, Hanne M.

    2008-01-01

    centres participated. This work also included a definition of the tissue structures needed to be outlined on the planning CT-scan. The work was initiated in 2003 and the guidelines were approved by the DBCG Radiotherapy Committee in 2006. The first of January 2007 the 3D guidelines had been fully...

  14. cGAS/STING Pathway in Cancer: Jekyll and Hyde Story of Cancer Immune Response.

    Science.gov (United States)

    Bose, Debojit

    2017-11-18

    The last two decades have witnessed enormous growth in the field of cancer immunity. Mechanistic insights of cancer immunoediting have not only enhanced our understanding but also paved the way to target and/or harness the innate immune system to combat cancer, called cancer immunotherapy. Cyclic GMP-AMP synthase (cGAS)/Stimulator of interferon genes(STING) pathway has recently emerged as nodal player in cancer immunity and is currently being explored as potential therapeutic target. Although therapeutic activation of this pathway has shown promising anti-tumor effects in vivo, evidence also indicates the role of this pathway in inflammation mediated carcinogenesis. This review highlights our current understanding of cGAS/STING pathway in cancer, its therapeutic targeting and potential alternate approaches to target this pathway. Optimal therapeutic targeting and artificial tunability of this pathway still demand in depth understanding of cGAS/STING pathway regulation and homeostasis.

  15. cGAS/STING Pathway in Cancer: Jekyll and Hyde Story of Cancer Immune Response

    Directory of Open Access Journals (Sweden)

    Debojit Bose

    2017-11-01

    Full Text Available The last two decades have witnessed enormous growth in the field of cancer immunity. Mechanistic insights of cancer immunoediting have not only enhanced our understanding but also paved the way to target and/or harness the innate immune system to combat cancer, called cancer immunotherapy. Cyclic GMP-AMP synthase (cGAS/Stimulator of interferon genes(STING pathway has recently emerged as nodal player in cancer immunity and is currently being explored as potential therapeutic target. Although therapeutic activation of this pathway has shown promising anti-tumor effects in vivo, evidence also indicates the role of this pathway in inflammation mediated carcinogenesis. This review highlights our current understanding of cGAS/STING pathway in cancer, its therapeutic targeting and potential alternate approaches to target this pathway. Optimal therapeutic targeting and artificial tunability of this pathway still demand in depth understanding of cGAS/STING pathway regulation and homeostasis.

  16. Association of interleukin-1β -511 C/T polymorphism with tobacco-associated cancer in northeast India: a study on oral and gastric cancer.

    Science.gov (United States)

    Lakhanpal, Meena; Yadav, Dhirendra Singh; Devi, Thoudam Regina; Singh, Laishram Chandreshwor; Singh, Khangembam Jitenkumar; Latha, Santhi P; Chauhan, Pradeep Singh; Verma, Yogesh; Zomavia, Eric; Sharma, Jagannath; Chandra Kataki, Amal; Saxena, Sunita; Kapur, Sujala

    2014-01-01

    The IL-1β -511 C/T polymorphism is associated with increased IL-1 production and with increased risk of developing cancers. In this study, 251 patients (125 with gastric cancer [GC] and 126 with oral cancer [OC]) and 207 normal controls from northeast (NE) India were genotyped for the IL-1β -511 C/T polymorphism by PCR-restriction fragment length polymorphism (RFLP) and sequencing. Analysis of results showed betel-quid chewing to be a major risk factor (OR = 2.01, 95% CI = 1.05-3.87; P = 0.035) for OC. Inheritance of the IL-1β -511 CT or TT resulted in a 2.6- to 3.05-fold increase in the risk of developing OC relative to that of participants who possessed the reference genotype (OR = 2.57, 95% CI = 1.06-6.22; P = 0.036 and OR = 3.05, 95% CI = 1.22-7.63; P = 0.017), after adjusting for potential confounders. The dominant genetic model also confirmed the presence of the T allele as a significant risk factor for OC (OR = 2.72, 95% CI = 1.15-6.42; P = 0.02). In GC, interaction of the CT genotype with tobacco and betel-quid chewing habits conferred a significant 78% and 89% reduced risk of cancer, respectively. In conclusion, for the NE Indian population, the IL-1β -511 CC and CT genotypes were significantly associated with increased risk of OC. However, the interaction of the CT genotype with risk habits may play a preventive role for GC but not for OC. Copyright © 2014 Elsevier Inc. All rights reserved.

  17. Mortality and recurrence rates among systemically untreated high risk breast cancer patients included in the DBCG 77 trials

    DEFF Research Database (Denmark)

    Jensen, Maj Britt; Nielsen, Torsten O.; Knoop, Ann S.

    2018-01-01

    Background: Following loco-regional treatment for early breast cancer accurate prognostication is essential for communicating benefits of systemic treatment. The aim of this study was to determine time to recurrence and long-term mortality rates in high risk patients according to patient characte......Background: Following loco-regional treatment for early breast cancer accurate prognostication is essential for communicating benefits of systemic treatment. The aim of this study was to determine time to recurrence and long-term mortality rates in high risk patients according to patient...... and EGFR positive. Multivariate categorical and fractional polynomials (MFP) models were used to construct prognostic subsets by clinicopathologic characteristics. Results: In a multivariate model, mortality rate was significantly associated with age, tumor size, nodal status, invasion, histological type...

  18. Isocitrate dehydrogenase 1 R132C mutation occurs exclusively in microsatellite stable colorectal cancers with the CpG island methylator phenotype.

    Science.gov (United States)

    Whitehall, V L J; Dumenil, T D; McKeone, D M; Bond, C E; Bettington, M L; Buttenshaw, R L; Bowdler, L; Montgomery, G W; Wockner, L F; Leggett, B A

    2014-11-01

    The CpG Island Methylator Phenotype (CIMP) is fundamental to an important subset of colorectal cancer; however, its cause is unknown. CIMP is associated with microsatellite instability but is also found in BRAF mutant microsatellite stable cancers that are associated with poor prognosis. The isocitrate dehydrogenase 1 (IDH1) gene causes CIMP in glioma due to an activating mutation that produces the 2-hydroxyglutarate oncometabolite. We therefore examined IDH1 alteration as a potential cause of CIMP in colorectal cancer. The IDH1 mutational hotspot was screened in 86 CIMP-positive and 80 CIMP-negative cancers. The entire coding sequence was examined in 81 CIMP-positive colorectal cancers. Forty-seven cancers varying by CIMP-status and IDH1 mutation status were examined using Illumina 450K DNA methylation microarrays. The R132C IDH1 mutation was detected in 4/166 cancers. All IDH1 mutations were in CIMP cancers that were BRAF mutant and microsatellite stable (4/45, 8.9%). Unsupervised hierarchical cluster analysis identified an IDH1 mutation-like methylation signature in approximately half of the CIMP-positive cancers. IDH1 mutation appears to cause CIMP in a small proportion of BRAF mutant, microsatellite stable colorectal cancers. This study provides a precedent that a single gene mutation may cause CIMP in colorectal cancer, and that this will be associated with a specific epigenetic signature and clinicopathological features.

  19. Measurement of urinary calcium using AT89C51RD2 microcontroller.

    Science.gov (United States)

    Neelamegam, P; Jamaludeen, A; Rajendran, A; Raghunathan, R

    2009-04-01

    A simple and inexpensive absorption technique for determination of calcium ion in urine samples is developed, comprising a light emitting diode (650 nm) as the light source and photodiode as the detector with AT89C51RD2 microcontroller. The design of the system and details of interface, calibration, and procedure of operation are explained in this paper. Software is developed to monitor sample processing and to display the results in liquid crystal display screen. With 15 microl sample volume, a linear output is obtained in the range of 2.5-7.5 mM calcium with a detection limit of 0.06 mM. Interferences from other cations such as monovalent ion and divalent ion are investigated in the expected range, which are normally present in clinical samples, and absorption changes over the pH range of 3-12 are also determined. This system has been demonstrated successfully for the successive assay of calcium in urine samples, with the results comparing well to those achieved and in good agreement with values obtained with the current clinical spectrophotometric method at 95% of confidence level.

  20. Study of {Lambda}{sup +}{sub c} production and Pentaquark search in WA89 CERN experiment data; Etude de la production du {Lambda}{sup +}{sub c} et recherche du Pentaquark dans les donnees de l`experience WA89 du CERN

    Energy Technology Data Exchange (ETDEWEB)

    Charignon, F

    1995-01-01

    This thesis is dedicated to the study of the {Lambda}{sub c}{sup +} charmed baryon and to the ``Pentaquark`` search, within the framework of the CERN WA89 experiment. This fixed target experiment is using a 330 GeV/c hyperon beam. Its aim is the production and the study of baryons carrying charm and strangeness as well as the search of multiquarks. The experimental setup is built around the CERN Omega spectrometer. Production and decay vertices of charmed particles are reconstructed by means of microstrip detectors. Multiwire proportional chambers reconstruct the trajectories in the Omega magnetic field and particle identification is provided by a Ring Imaging Cherenkov detector. An invariant mass signal has been obtained for the {Lambda}{sub c}{sup +} in the proton-kaon-pion decay channel. Distorsion effects occurring in the event reconstruction have been taken into account in the estimation of the {Lambda}{sub c}{sup +} lifetime and production cross-section. Finally, the exotic multiquark state ``Pentaquark`` was investigated in the channel proton-phi-pion but no signal was observed. (author). 86 refs., 56 figs.

  1. The unpaved journey of vitamin C in cancer treatment.

    Science.gov (United States)

    Chen, Qi; Polireddy, Kishore; Chen, Ping; Dong, Ruochen

    2015-12-01

    Effectiveness and low-toxicity to normal tissues are ideal properties for a cancer treatment, and one that numerous research programs are aiming for. Vitamin C has long been used in the field of Complementary and Alternative Medicine as a cancer treatment, with profound safety and anecdotal efficacy. Recent studies revealed the scientific basis for this use, and indicated that vitamin C, at supra-nutritional doses, holds considerable promise as an effective and low-toxic therapeutic strategy to treat cancer. Reviewed here are the early controversies surrounding vitamin C and cancer treatment, the breakthrough discoveries that led to the current advancement, and recent clinical studies, as well as research into its mechanisms of action.

  2. c-Raf in KRas Mutant Cancers: A Moving Target.

    Science.gov (United States)

    McCormick, Frank

    2018-02-12

    Therapies for KRas cancers remain a major clinical need. In the current issue of Cancer Cell, Sanclemente and coworkers in Mariano Barbacid's group validate c-Raf as a prime target for these cancers. c-Raf ablation caused regression of advanced KRas G12V /Trp53 tumors, without obvious systemic toxicity and without affecting MAPK signaling. Copyright © 2018 Elsevier Inc. All rights reserved.

  3. The TFIIH Subunit p89 (XPB Localizes to the Centrosome during Mitosis

    Directory of Open Access Journals (Sweden)

    Achim Weber

    2010-01-01

    Full Text Available Background: The general transcription factor II H (TFIIH, comprised of a core complex and an associated CAK-complex, functions in transcription, DNA repair and cell cycle control. Mutations of the two largest subunits, p89 (XPB and p80 (XPD, cause the hereditary cancer-prone syndrome xeroderma pigmentosum.

  4. Nuclear osteopontin-c is a prognostic breast cancer marker.

    Science.gov (United States)

    Zduniak, K; Ziolkowski, P; Ahlin, C; Agrawal, A; Agrawal, S; Blomqvist, C; Fjällskog, M-L; Weber, G F

    2015-02-17

    Although Osteopontin has been known as a marker for cancer progression, the elevated production of this cytokine is not specific for cancer. We have identified the splice variant Osteopontin-c as being absent from healthy tissue but associated with about 75% of breast cancer cases. However, in previous studies of Osteopontin-c, follow-up information was not available. Here we have analysed 671 patients, comprising a cohort of 291 paraffin blocks plus a population-based case-control study of 380 arrayed breast tumor tissues. We find that high staining intensity of nuclear Osteopontin-c is strongly associated with mortality in patients with early breast cancer. Cytosolic staining for exon 4, reflective of Osteopontin-a and -b also predicts poor outcome. By contrast, total Osteopontin does not correlate with prognosis. These diverse assessments of Osteopontin also do not correlate with each other, suggesting distinct expression patterns for the variant forms. Consistent with its role in tumor progression, not tumor initiation, Osteopontin-c is not correlated with proliferation markers (Ki-67, cyclin A, cyclin B, cyclin E and cyclin D), neither is it correlated with ER, PR or HER2. The addition of Osteopontin-c immunohistochemistry to standard pathology work-ups may have prognostic benefit in early breast cancer diagnosis.

  5. 40 CFR 89.404 - Test procedure overview.

    Science.gov (United States)

    2010-07-01

    ... engine operating conditions to be conducted on an engine dynamometer. The exhaust gases, generated raw or... matter. For more information on particulate matter sampling see § 89.112(c). The test cycles consist of... (raw analysis), and the power output during each mode. The measured values are weighted and used to...

  6. The cytosolic chaperonin CCT/TRiC and cancer cell proliferation.

    Directory of Open Access Journals (Sweden)

    Chafika Boudiaf-Benmammar

    Full Text Available The molecular chaperone CCT/TRiC plays a central role in maintaining cellular proteostasis as it mediates the folding of the major cytoskeletal proteins tubulins and actins. CCT/TRiC is also involved in the oncoprotein cyclin E, the Von Hippel-Lindau tumour suppressor protein, cyclin B and p21(ras folding which strongly suggests that it is involved in cell proliferation and tumor genesis. To assess the involvement of CCT/TRiC in tumor genesis, we quantified its expression levels and activity in 18 cancer, one non-cancer human cell lines and a non-cancer human liver. We show that the expression levels of CCT/TRiC in cancer cell lines are higher than that in normal cells. However, CCT/TRiC activity does not always correlate with its expression levels. We therefore documented the expression levels of CCT/TRiC modulators and partners PhLP3, Hop/P60, prefoldin and Hsc/Hsp70. Our analysis reveals a functional interplay between molecular chaperones that might account for a precise modulation of CCT/TRiC activity in cell proliferation through changes in the cellular levels of prefoldin and/or Hsc/p70 and CCT/TRiC client protein availability. Our observation and approaches bring novel insights in the role of CCT/TRiC-mediated protein folding machinery in cancer cell development.

  7. Nucleus--nucleus total cross sections for light nuclei at 1.55 and 2.89 GeV/C/nucleon

    International Nuclear Information System (INIS)

    Jaros, J.A.

    1975-11-01

    Total cross sections have been measured for protons, deuterons, alphas, and 12 C on hydrogen, deuterium, helium, and carbon targets at 1.55 and 2.89 GeV/c/nucleon using the ''good geometry'' transmission method. In addition, the inelastic cross sections and elastic slope parameters were measured for reactions initiated by deuterons, alphas, and 12 C. The factorization relation sigma/sub T/(AA) = sigma/sub T/(AB) 2 /sigma/sub T/(BB) is violated for some of these reactions. The results generally agree with Glauber theory predictions except in their detailed energy behavior. It is found that sigma/sub T/ approximately equal to 144 (A/sub T//sup 1 / 3 / + A/sub P//sup 1 / 3 / - 1.48) 2 and sigma/sub IN/ approximately equal to 78 (A/sub T//sup 1 / 3 / + A/sub P//sup 1 / 3 / - 1.25) 2 , where A/sub T/(A/sub P/) is the atomic mass number of the target (projectile) and the cross sections are given in mb

  8. Application of 11C-choline PET/CT imaging for differentiating malignant from benign prostate lesions

    International Nuclear Information System (INIS)

    Li Xin; Wang Muwen; Liu Qingwei; Zhu Renjuan; Liu Lihui; Yuan Xianshun; Yao Shuzhan; Liu Songtao

    2006-01-01

    Objective: To investigate the potential of 11 C-choline PET/CT imaging for differentiating prostate cancer from benign prostate hyperplasia. Methods: A total of 45 patients with prostate lesions under- went 11 C-choline PET/CT imaging before transrectal needle biopsy. PET/CT imaging was performed 5 min after injection of 7.4 MBq/kg 11 C-choline in supine position over lower abdomen (3 min per bed with 2 beds), including the pelvis, and the whole body with 6 beds when necessary. After attenuation correction and iterative reconstruction, PET data were analyzed semi-quantitatively by measuring maximum standardized uptake values (SUV max ) in prostate lesions (P, target) and the muscles (M, non-target) and then P/M ratios were calculated. Also visual analysis was performed in different transverse, sagittal views and slices as well as three-dimensional images. Results: Eighteen prostate cancer and 27 benign prostate hyperplasia [and(or) chronic prostatitis] were all confirmed by pathology. The mean P/M ratio of prostate cancer was 4.02± 1.88, while in benign lesions was 1.87±1.21. The statistical differences of P/M ratios between them were significant (t=2.07, P 11 C-choline PET/CT imaging were 88.89%, 88.89% and 92.31% respectively. Conclusions: 11 C-choline PET/CT imaging is a valuable non-invasive technology in the diagnosis of pros- tate cancer. The P/M ratio can differentiate prostate cancer from benign lesions better than SUV. (authors)

  9. Prostaglandin E2 and the protein kinase A pathway mediate arachidonic acid induction of c-fos in human prostate cancer cells

    Science.gov (United States)

    Chen, Y.; Hughes-Fulford, M.

    2000-01-01

    Arachidonic acid (AA) is the precursor for prostaglandin E2 (PGE2) synthesis and increases growth of prostate cancer cells. To further elucidate the mechanisms involved in AA-induced prostate cell growth, induction of c-fos expression by AA was investigated in a human prostate cancer cell line, PC-3. c-fos mRNA was induced shortly after addition of AA, along with a remarkable increase in PGE2 production. c-fos expression and PGE2 production induced by AA was blocked by a cyclo-oxygenase inhibitor, flurbiprofen, suggesting that PGE2 mediated c-fos induction. Protein kinase A (PKA) inhibitor H-89 abolished induction of c-fos expression by AA, and partially inhibited PGE2 production. Protein kinase C (PKC) inhibitor GF109203X had no significant effect on c-fos expression or PGE2 production. Expression of prostaglandin (EP) receptors, which mediate signal transduction from PGE2 to the cells, was examined by reverse transcription polymerase chain reaction in several human prostate cell lines. EP4 and EP2, which are coupled to the PKA signalling pathway, were expressed in all cells tested. Expression of EP1, which activates the PKC pathway, was not detected. The current study showed that induction of the immediate early gene c-fos by AA is mediated by PGE2, which activates the PKA pathway via the EP2/4 receptor in the PC-3 cells.

  10. Low background α β measuring and acquisition PC card based on single chip microcomputer 89C51 and Max528 DAC

    International Nuclear Information System (INIS)

    Liu Weihong; Pan Zhongtao; Zhang Liqiong

    1996-01-01

    A low background α β measuring and data acquisition PC card based on 89C51 microcomputer and eight bites eight channels digital to analog converter are introduced. It has four digital threshold adjustments and two high voltage controllers on one card and has functions of processing signals from nuclear detector, such as amplifying, comparing, shaping, coincidence or anti-coincidence, counting and saving data

  11. Effective dose to immuno-PET patients due to metastable impurities in cyclotron produced zirconium-89

    Science.gov (United States)

    Alfuraih, Abdulrahman; Alzimami, Khalid; Ma, Andy K.; Alghamdi, Ali; Al Jammaz, Ibrahim

    2014-11-01

    Immuno-PET is a nuclear medicine technique that combines positron emission tommography (PET) with radio-labeled monoclonal antibodies (mAbs) for tumor characterization and therapy. Zirconium-89 (89Zr) is an emerging radionuclide for immuno-PET imaging. Its long half-life (78.4 h) gives ample time for the production, the administering and the patient uptake of the tagged radiopharmaceutical. Furthermore, the nuclides will remain in the tumor cells after the mAbs are catabolized so that time series studies are possible without incurring further administration of radiopharmarceuticals. 89Zr can be produced in medical cyclotrons by bombarding an yttrium-89 (89Y) target with a proton beam through the 89Y(p,n)89Zr reaction. In this study, we estimated the effective dose to the head and neck cancer patients undergoing 89Zr-based immune-PET procedures. The production of 89Zr and the impurities from proton irradiation of the 89Y target in a cyclotron was calculated with the Monte Carlo code MCNPX and the nuclear reaction code TALYS. The cumulated activities of the Zr isotopes were derived from real patient data in literature and the effective doses were estimated using the MIRD specific absorbed fraction formalism. The estimated effective dose from 89Zr is 0.5±0.2 mSv/MBq. The highest organ dose is 1.8±0.2 mSv/MBq in the liver. These values are in agreement with those reported in literature. The effective dose from 89mZr is about 0.2-0.3% of the 89Zr dose in the worst case. Since the ratio of 89mZr to 89Zr depends on the cooling time as well as the irradiation details, contaminant dose estimation is an important aspect in optimizing the cyclotron irradiation geometry, energy and time.

  12. RELATIONSHIP BETWEEN TYPE C BEHAVIOR AND BREAST CANCER

    Directory of Open Access Journals (Sweden)

    ÁNGELA MARÍA TORRES MARIÑO

    2006-10-01

    Full Text Available The main objective of this study was to investigate deeply the relationship between Type C behavior pattern andbreast cancer through an analytical observation design of cases and controls. Three groups of variables were established:demographical, medical and risk factors, including in the last one the Type C behavior, for three groups: a women withbreast cancer, b women with cervix cancer, and c healthy women. The changing answer for ‘having breast cancer’ isdetermined by the family history of sickness, having hormone replace therapy, the history of the ovarian and endometrialcancer, and the age of the participants. One concludes that the behavior pattern, so and as is raised until the moment,is related more to the way the disease is faced, than a type of premorbid personality. New factors are proposed in baseof the Five Factor Model, the Temperament and Character set out.

  13. Receptor tyrosine kinase (c-Kit inhibitors: a potential therapeutic target in cancer cells

    Directory of Open Access Journals (Sweden)

    Abbaspour Babaei M

    2016-08-01

    Full Text Available Maryam Abbaspour Babaei,1 Behnam Kamalidehghan,2,3 Mohammad Saleem,4–6 Hasniza Zaman Huri,1,7 Fatemeh Ahmadipour1 1Department of Pharmacy, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia; 2Department of Medical Genetics, National Institute of Genetic Engineering and Biotechnology (NIGEB, Shahrak-e Pajoohesh, 3Medical Genetics Department, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran; 4Department of Urology, 5Department of Laboratory Medicine and Pathology, Masonic Cancer Center, University of Minnesota, 6Section of Molecular Therapeutics & Cancer Health Disparity, The Hormel Institute, Austin, MN, USA; 7Clinical Investigation Centre, University Malaya Medical Centre, Lembah Pantai, Kuala Lumpur, Malaysia Abstract: c-Kit, a receptor tyrosine kinase, is involved in intracellular signaling, and the mutated form of c-Kit plays a crucial role in occurrence of some cancers. The function of c-Kit has led to the concept that inhibiting c-Kit kinase activity can be a target for cancer therapy. The promising results of inhibition of c-Kit for treatment of cancers have been observed in some cancers such as gastrointestinal stromal tumor, acute myeloid leukemia, melanoma, and other tumors, and these results have encouraged attempts toward improvement of using c-Kit as a capable target for cancer therapy. This paper presents the findings of previous studies regarding c-Kit as a receptor tyrosine kinase and an oncogene, as well as its gene targets and signaling pathways in normal and cancer cells. The c-Kit gene location, protein structure, and the role of c-Kit in normal cell have been discussed. Comprehending the molecular mechanism underlying c-Kit-mediated tumorogenesis is consequently essential and may lead to the identification of future novel drug targets. The potential mechanisms by which c-Kit induces cellular transformation have been described. This study aims to elucidate the function of c

  14. Danish Breast Cancer Cooperative Group--DBCG: History, organization, and status of scientific achievements at 30-year anniversary

    DEFF Research Database (Denmark)

    Blichert-Toft, M.; Christiansen, Peter; Mouridsen, H.T.

    2008-01-01

    treatment programmes including in situ lesions and primary invasive breast cancer. Probands are subdivided into risk groups based on a given risk pattern and allocated to various treatment programmes accordingly. The scientific initiatives are conducted in the form of register- and cohort analysis...... on a risk scale. The main achievements resulted in a reduction of relative risk of death amounting up to 20% and increased 5-year overall survival ascending from 60% to roughly 80%. This article is partly based on a Danish paper to be published in the Centenary Jubilee book of the Danish Surgical Society...

  15. Correlation of the secretion of insulin and C-peptide in cancer patients

    Energy Technology Data Exchange (ETDEWEB)

    Modnikov, O P; Lomtev, N G [Kirgizskij Nauchno-Issledovatel' skij Inst. Onkologii i Radiologii, Frunze (USSR)

    1983-08-01

    Insulin and C-peptide levels were studied with a radioimmunoassay in the peripheral blood serum of 44 patients with gastric and cervical cancer and 22 healthy persons. Hyperfunction of the pancreatic insular apparatus was shown in cancer patients which was expressed in a statistically significant increase in the C-peptide level. In gastric cancer patients hyperfunction of the insular apparatus was accompanied by hypoinsulinemia, and in cervical cancer patients by hormoinsulinemia. An analysis has shown that the ratio insulin/C-peptide in gastric and cervical cancer patients was about the same and significantly lower than the control. A conclusion has been made that in spite of difference in the initial insulin concentration, the same phenomenon - acceleration of the metabolic clearance of insulin - occurs in patients with cancer of the above sites. The C-peptide level decreased, the ratio insulin/C-peptide increased, i.e. hyperfunction of the insular apparatus disappeared and the metabolic clearance of insulin slowed down.

  16. Correlation of the sectetion of insulin and C-peptide in cancer patients

    International Nuclear Information System (INIS)

    Modnikov, O.P.; Lomtev, N.G.

    1983-01-01

    Insulin and C-peptide levels were studied with a radioimmunoassay in the peripheral blood serum of 44 patients with gastric and cervical cancer and 22 healthy persons. Hyperfunction of the pancreatic insular apparatus was shown in cancer patients which was expressed in a statistically significant increase in the C-peptide level. In gastric cancer patients hyperfunction of the insular apparatus was accompanied by hypoinsulinemia, and in cervical cancer patients by hormoinsulinemia. An analysis has shown that the ratio insulin/C-peptide in gastric and cervical cancer patients was about the same and significantly lower than the control. A conclusion has been made that in spite of difference in the initial insulin concentration, the same phenomenon - acceleration of the metabolic clearance of insulin - occurs in patients with cancer of the above sites. The C-peptide level decreased, the ratio insulin/C-peptide increased, i.e. hyperfunction of the insular apparatus disappeared and the metabolic clearance of insulin slowed down

  17. 29 CFR 1960.89 - Organization.

    Science.gov (United States)

    2010-07-01

    ... 29 Labor 9 2010-07-01 2010-07-01 false Organization. 1960.89 Section 1960.89 Labor Regulations Relating to Labor (Continued) OCCUPATIONAL SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF LABOR (CONTINUED... Field Federal Safety and Health Councils § 1960.89 Organization. (a) Field council officers shall...

  18. The polymorphism of CYP2E1 Rsa I/Pst I gene and susceptibility to respiratory system cancer: a systematic review and meta-analysis of 34 studies.

    Science.gov (United States)

    Xu, Li; Yang, Mingyuan; Zhao, Tiejun; Jin, Hai; Xu, Zhiyun; Li, Ming; Chen, Hezhong

    2014-12-01

    The purpose of this articles is to determine whether the cytochrome P450 2E1 (CYP2E1) Rsa I/Pst I gene polymorphism is correlated with respiratory system cancers. Respiratory system cancers included lung cancer, laryngeal cancer, nasopharyngeal cancer, and cancers of other respiratory organs, which are the most common malignant tumors worldwide; the significant relationship between CYP2E1 Rsa I/Pst I gene polymorphism and some respiratory system cancer have been reported, but results of some other studies are controversial. The pooled odds ratio (OR) with 95% confidence interval (CI) was calculated to assess the association. PubMed, EMBASE, Cochrane Library Databases, China National Knowledge Infrastructure, and Wanfang Database (up to July 20, 2014) were searched for all case-control studies those mainly studied the relationship between CYP2E1 Rsa I/Pst I gene polymorphism and the susceptibility of respiratory system cancer. A total of 332 articles were collected, among which 34 studies that involved 7028 cases and 9822 controls fulfilled the inclusion criteria after being assessed by 2 reviewers. When stratified by cancer site, the C2/C2 polymorphism could increase the risk of nasopharyngeal cancer under the homozygote model (C2C2 vs C1C1: OR = 1.85, 95% CI = 1.20-2.85, P = 0.005) and recessive model (C2C2 vs C1C2/C1C1: OR = 1.89, 95% CI = 1.23-2.89, P = 0.003). Protection effect was found in lung cancer in heterozygote model (C1C2 vs C1C1: OR = 0.82, 95% CI = 0.74-0.91, P Rsa I/Pst I gene polymorphism may reduce the risk of respiratory system cancer. Furthermore, significant association was also found in Asian populations.

  19. A study of the 89Y (n,n'γ)89Y reaction

    International Nuclear Information System (INIS)

    Nardelli, G.; Tornielli, G.

    1985-01-01

    Energy levels of 89 Y were populated by the 89 Y(n,n'γ) reaction at neutron energies between 2.2 and 4.8 MeV. A time gated (HP)Ge spectrometer was used to detect the deexcitation γ-rays. Forty-three levels through 4537 KeV excitation energy were identified in this way, two of which were previously unreported. Spins and parities were determined within the framework of the statistical theory from the angular distributions and excitation functions of the observed γ-rays. A complete level and decay scheme for 89 Y up to an excitation of 4.32 MeV is presented

  20. 14 CFR 151.89 - Roads.

    Science.gov (United States)

    2010-01-01

    ... 14 Aeronautics and Space 3 2010-01-01 2010-01-01 false Roads. 151.89 Section 151.89 Aeronautics... AID TO AIRPORTS Project Programming Standards § 151.89 Roads. (a) Federal-aid Airport Program funds may not be used to resolve highway problems. Only those airport entrance roads that are definitely...

  1. 40 CFR 89.206 - Trading.

    Science.gov (United States)

    2010-07-01

    ... 40 Protection of Environment 20 2010-07-01 2010-07-01 false Trading. 89.206 Section 89.206... EMISSIONS FROM NEW AND IN-USE NONROAD COMPRESSION-IGNITION ENGINES Averaging, Banking, and Trading Provisions § 89.206 Trading. (a) Requirements for Tier 1 engines rated at or above 37 kW. (1) A nonroad...

  2. 40 CFR 89.205 - Banking.

    Science.gov (United States)

    2010-07-01

    ... 40 Protection of Environment 20 2010-07-01 2010-07-01 false Banking. 89.205 Section 89.205... EMISSIONS FROM NEW AND IN-USE NONROAD COMPRESSION-IGNITION ENGINES Averaging, Banking, and Trading Provisions § 89.205 Banking. (a) Requirements for Tier 1 engines rated at or above 37 kW. (1) A manufacturer...

  3. Site-specifically {sup 89}Zr-labeled monoclonal antibodies for ImmunoPET

    Energy Technology Data Exchange (ETDEWEB)

    Tinianow, Jeff N.; Gill, Herman S.; Ogasawara, Annie; Flores, Judith E.; Vanderbilt, Alexander N.; Luis, Elizabeth; Vandlen, Richard; Darwish, Martine; Junutula, Jagath R.; Williams, Simon-P. [Genentech Research and Early Development, Genentech Inc., South San Francisco, CA 94080 (United States); Marik, Jan [Genentech Research and Early Development, Genentech Inc., South San Francisco, CA 94080 (United States)], E-mail: marik.jan@gene.com

    2010-04-15

    Three thiol reactive reagents were developed for the chemoselective conjugation of desferrioxamine (Df) to a monoclonal antibody via engineered cysteine residues (thio-trastuzumab). The in vitro stability and in vivo imaging properties of site-specifically radiolabeled {sup 89}Zr-Df-thio-trastuzumab conjugates were investigated. Methods: The amino group of desferrioxamine B was acylated by bromoacetyl bromide, N-hydroxysuccinimidyl iodoacetate, or N-hydroxysuccinimidyl 4-[N-maleimidomethyl]cyclohexane-1-carboxylate to obtain thiol reactive reagents bromoacetyl-desferrioxamine (Df-Bac), iodoacetyl-desferrioxamine (Df-Iac) and maleimidocyclohexyl-desferrioxamine (Df-Chx-Mal), respectively. Df-Bac and Df-Iac alkylated the free thiol groups of thio-trastuzumab by nucleophilic substitution forming Df-Ac-thio-trastuzumab, while the maleimide reagent Df-Chx-Mal reacted via Michael addition to provide Df-Chx-Mal-thio-trastuzumab. The conjugates were radiolabeled with {sup 89}Zr and evaluated for serum stability, and their positron emission tomography (PET) imaging properties were investigated in a BT474M1 (HER2-positive) breast tumor mouse model. Results: The chemoselective reagents were obtained in 14% (Df-Bac), 53% (Df-Iac) and 45% (Df-Chx-Mal) yields. Site-specific conjugation of Df-Chx-Mal to thio-trastuzumab was complete within 1 h at pH 7.5, while Df-Iac and Df-Bac respectively required 2 and 5 h at pH 9. Each Df modified thio-trastuzumab was chelated with {sup 89}Zr in yields exceeding 75%. {sup 89}Zr-Df-Ac-thio-trastuzumab and {sup 89}Zr-Df-Chx-Mal-thio-trastuzumab were stable in mouse serum and exhibited comparable PET imaging capabilities in a BT474M1 (HER2-positive) breast cancer model reaching 20-25 %ID/g of tumor uptake and a tumor to blood ratio of 6.1-7.1. Conclusions: The new reagents demonstrated good reactivity with engineered thiol groups of trastuzumab and very good chelation properties with {sup 89}Zr. The site-specifically {sup 89}Zr-labeled thio

  4. Characterization of ORF89 - A latency-related gene of white spot syndrome virus

    International Nuclear Information System (INIS)

    Hossain, M.S.; Khadijah, Siti; Kwang, Jimmy

    2004-01-01

    Open reading frame 89 (ORF89) is one of the three genes that are believed to be involved in the latent infection of white spot syndrome virus (WSSV). Here, we report the structure and functional characterization of ORF89. cDNA sequencing, 5' RLM-RACE, and 3' RLM-RACE showed that ORF89 gene is transcribed into an unspliced mRNA of 4436 nucleotides, which is predicted to encode a protein of 1437 amino acids. ORF89 expressed an approximately 165-kDa protein in Sf9 cells that localized in the nucleus. Amino acids 678-683 were found to be essential for nuclear localization. Cotransfection assays demonstrated that ORF89 protein repressed its own promoter as well as those of a protein kinase and the thymidine-thymidylate kinase genes of WSSV. SYBR Green real-time PCR indicated that the repression occurred at the transcriptional level

  5. Deep phenotyping of 89 xeroderma pigmentosum patients reveals unexpected heterogeneity dependent on the precise molecular defect

    Science.gov (United States)

    Fassihi, Hiva; Sethi, Mieran; Fawcett, Heather; Wing, Jonathan; Chandler, Natalie; Mohammed, Shehla; Craythorne, Emma; Morley, Ana M. S.; Lim, Rongxuan; Turner, Sally; Henshaw, Tanya; Garrood, Isabel; Giunti, Paola; Hedderly, Tammy; Abiona, Adesoji; Naik, Harsha; Harrop, Gemma; McGibbon, David; Jaspers, Nicolaas G. J.; Botta, Elena; Nardo, Tiziana; Stefanini, Miria; Young, Antony R.; Sarkany, Robert P. E.; Lehmann, Alan R.

    2016-01-01

    Xeroderma pigmentosum (XP) is a rare DNA repair disorder characterized by increased susceptibility to UV radiation (UVR)-induced skin pigmentation, skin cancers, ocular surface disease, and, in some patients, sunburn and neurological degeneration. Genetically, it is assigned to eight complementation groups (XP-A to -G and variant). For the last 5 y, the UK national multidisciplinary XP service has provided follow-up for 89 XP patients, representing most of the XP patients in the United Kingdom. Causative mutations, DNA repair levels, and more than 60 clinical variables relating to dermatology, ophthalmology, and neurology have been measured, using scoring systems to categorize disease severity. This deep phenotyping has revealed unanticipated heterogeneity of clinical features, between and within complementation groups. Skin cancer is most common in XP-C, XP-E, and XP-V patients, previously considered to be the milder groups based on cellular analyses. These patients have normal sunburn reactions and are therefore diagnosed later and are less likely to adhere to UVR protection. XP-C patients are specifically hypersensitive to ocular damage, and XP-F and XP-G patients appear to be much less susceptible to skin cancer than other XP groups. Within XP groups, different mutations confer susceptibility or resistance to neurological damage. Our findings on this large cohort of XP patients under long-term follow-up reveal that XP is more heterogeneous than has previously been appreciated. Our data now enable provision of personalized prognostic information and management advice for each XP patient, as well as providing new insights into the functions of the XP proteins. PMID:26884178

  6. Effect of high-dose intravenous vitamin C on inflammation in cancer patients

    Directory of Open Access Journals (Sweden)

    Mikirova Nina

    2012-09-01

    Full Text Available Abstract Background An inflammatory component is present in the microenvironment of most neoplastic tissues. Inflammation and elevated C-reactive protein (CRP are associated with poor prognosis and decreased survival in many types of cancer. Vitamin C has been suggested as having both a preventative and therapeutic role in a number of pathologies when administered at much higher-than-recommended dietary allowance levels. Since in vitro studies demonstrated inhibition of pro-inflammatory pathways by millimolar concentrations of vitamin C, we decided to analyze the effects of high dose IVC therapy in suppression of inflammation in cancer patients. Methods 45 patients with prostate cancer, breast cancer, bladder cancer, pancreatic cancer, lung cancer, thyroid cancer, skin cancer and B-cell lymphoma were treated at the Riordan Clinic by high doses of vitamin C (7.5 g -50 g after standard treatments by conventional methods. CRP and tumor markers were measured in serum or heparin-plasma as a routine analysis. In addition, serum samples were collected before and after the IVCs for the cytokine kit tests. Results According to our data positive response to treatment, which was demonstrated by measurements of C- reactive protein, was found in 75% of patients and progression of the inflammation in 25% of patients. IVC treatments on all aggressive stage cancer patients showed the poor response of treatment. There was correlation between tumor markers (PSA, CEA, CA27.29 and CA15-3 and changes in the levels of C-reactive protein. Our test of the effect of IVC on pro-inflammatory cytokines demonstrated that inflammation cytokines IL-1α, IL-2, IL-8, TNF-α, chemokine eotaxin and CRP were reduced significantly after treatments. Conclusions The high dose intravenous ascorbic acid therapy affects C-reactive protein levels and pro-inflammation cytokines in cancer patients. In our study, we found that modulation of inflammation by IVC correlated with decreases

  7. Simulasi Penerapan Mikrokontroller At89c51 Dalam Proses Penyortiran Balok Kayu Berdasarkan Kriteria Panjang Dan Ketebalan

    Directory of Open Access Journals (Sweden)

    Arief Hendra Saptadi

    2008-08-01

    Full Text Available The main problem on sorting out the wood logs in traditional wood industry was that the process should be done manually. Hence, it required an automated system to perform sorting process with a higher precision level. The purpose of this research was to create a simulation of automated wood log sorting process based on specified length and thickness. The sorting system consisted of AT89C51 microcontroller system, keypad (in order to enter the required value of length and thickness, LCD (in order to display the result of sorting process, conveyor belt, two pairs of light sensor (consisting of photodiode and LED, each, and three DC motors which were driven by five relay circuits. At the beginning of sorting process, an operator was to type the selection range (i.e. the minimum and maximum value of required length and thickness via the keypad provided. The wood log mounted on conveyor belt would be measured by light sensors to determine the value of length and thickness. Based on the values, AT89C51 microcontroller system would then compare them to the selection range. If the log being sorted out fulfilled the requirements, it would be directed to "Accepted" compartment, or else to "Rejected" one. From the test performed, it was concluded that the length measurement was more precise for short logs. While the error rate was much higher for thin logs on thickness measurement. The process of sorting out and counting the wood logs was performed successfully. The system could use the narrowing mechanism at the mounting part of conveyor belt and better supporting ace on thickness sensor, in order to minimize the error rate on length and thickness measurement, respectively. In addition, the system could be developed to measure the volume of an object, providing that the object being measured was having a square or full-circle cross-sectional area.

  8. Lack of association between NADPH quinone oxidoreductase 1 (NQO1 gene C609T polymorphism and lung cancer: a case-control study and a meta-analysis.

    Directory of Open Access Journals (Sweden)

    Shujie Guo

    Full Text Available BACKGROUND: The association between NAD(PH:quinone oxidoreductase 1 (NQO1 gene C609T polymorphism (rs1800566 and lung cancer has been widely evaluated, and a definitive answer so far is lacking. We first conducted a case-control study to assess this association in northeastern Han Chinese, and then performed a meta-analysis to further address this issue. METHODOLOGY/PRINCIPAL FINDINGS: This case-control study involved 684 patients clinically diagnosed as lung cancer and 602 age-matched cancer-free controls from Harbin city, Heilongjiang province, China. Genotyping was conducted using the PCR-LDR (ligase detection reactions method. Meta-analysis was managed by STATA software. Data and study quality were assessed in duplicate. Our case-control association study indicated no significant difference in the genotype and allele distributions of C609T polymorphism between lung cancer patients and controls, consistent with the results of the further meta-analysis involving 7286 patients and 9167 controls under both allelic (odds ratio (OR = 0.99; 95% confidence interval (CI: 0.92-1.06; P = 0.692 and dominant (OR = 0.98; 95% CI: 0.89-1.08; P = 0.637 models. However, there was moderate evidence of between-study heterogeneity and low probability of publication bias. Further subgroup analyses by ethnicity, source of controls and sample size detected no positive associations in this meta-analysis. CONCLUSIONS: Our study in northeastern Han Chinese, along with the meta-analysis, failed to confirm the association of NQO1 gene C609T polymorphism with lung cancer risk, even across different ethnic populations.

  9. CHEK2∗1100delC Mutation and Risk of Prostate Cancer

    Directory of Open Access Journals (Sweden)

    Victoria Hale

    2014-01-01

    Full Text Available Although the causes of prostate cancer are largely unknown, previous studies support the role of genetic factors in the development of prostate cancer. CHEK2 plays a critical role in DNA replication by responding to double-stranded breaks. In this review, we provide an overview of the current knowledge of the role of a genetic variant, 1100delC, of CHEK2 on prostate cancer risk and discuss the implication for potential translation of this knowledge into clinical practice. Currently, twelve articles that discussed CHEK2∗1100delC and its association with prostate cancer were identified. Of the twelve prostate cancer studies, five studies had independent data to draw conclusive evidence from. The pooled results of OR and 95% CI were 1.98 (1.23–3.18 for unselected cases and 3.39 (1.78–6.47 for familial cases, indicating that CHEK2∗1100delC mutation is associated with increased risk of prostate cancer. Screening for CHEK2∗1100delC should be considered in men with a familial history of prostate cancer.

  10. Nutrition and cancer Nutrición y cáncer

    Directory of Open Access Journals (Sweden)

    WALTER C WILLETT

    1997-07-01

    Full Text Available Evidence from both animal and epidemiologic studies indicate that throughout life excessive energy intake in relation to requirements increases risk of human cancer. Rapid growth rates in childhood lead to earlier age at menarche, which in turn increases risk of breast cancer, and accumulation of body fat in adulthood in related to cancers of the colon, kidney, and endometrium as well as postmenopausal breast cancer. Higher intake of vegetables and fruits has been associated with lower risks of many cancers. The constituents responsible for these apparent protective effects remain uncertain, although evidence supports a contribution of folic acid. Recent evidence suggests that the percentage of energy from fat in the diet is not a major cause of cancers of the breast or colon. Higher intake of meat and dairy products has been associated with greater risk of prostate cancer, which may be related to their saturated fat content. Also, red meat consumption has been associated with risk of colon cancer in numerous studies, but this appears to be unrelated to its fat content. Excessive consumption of alcohol increases risks of upper gastrointestinal tract and even moderate intake appears to increase cancers of the breast and large bowel. Although many details remain to be learned, evidence is strong that remaining physically active and lean throughout life, consuming an abundance of fruits and vegetables, and avoiding high intakes of red meat, foods high in animal fat, and excessive alcohol will substantially reduce risk of human cancer.La evidencia que proporcionan tanto los estudios en animales como los epidemiológicos, indica que el consumo excesivo de energía incrementa el riesgo de cáncer en los humanos. Las tasas de crecimiento rápidas durante la niñez pueden conducir a una menarquia temprana, lo que aumenta el riesgo de cáncer de mama, y la acumulación de grasa corporal en la madurez está relacionada con el cáncer de colon, riñón y

  11. GUCY2C-directed CAR-T cells oppose colorectal cancer metastases without autoimmunity.

    Science.gov (United States)

    Magee, Michael S; Kraft, Crystal L; Abraham, Tara S; Baybutt, Trevor R; Marszalowicz, Glen P; Li, Peng; Waldman, Scott A; Snook, Adam E

    2016-01-01

    Adoptive T-cell therapy (ACT) is an emerging paradigm in which T cells are genetically modified to target cancer-associated antigens and eradicate tumors. However, challenges treating epithelial cancers with ACT reflect antigen targets that are not tumor-specific, permitting immune damage to normal tissues, and preclinical testing in artificial xenogeneic models, preventing prediction of toxicities in patients. In that context, mucosa-restricted antigens expressed by cancers exploit anatomical compartmentalization which shields mucosae from systemic antitumor immunity. This shielding may be amplified with ACT platforms employing antibody-based chimeric antigen receptors (CARs), which mediate MHC-independent recog-nition of antigens. GUCY2C is a cancer mucosa antigen expressed on the luminal surfaces of the intestinal mucosa in mice and humans, and universally overexpressed by colorectal tumors, suggesting its unique utility as an ACT target. T cells expressing CARs directed by a GUCY2C-specific antibody fragment recognized GUCY2C, quantified by expression of activation markers and cytokines. Further, GUCY2C CAR-T cells lysed GUCY2C-expressing, but not GUCY2C-deficient, mouse colorectal cancer cells. Moreover, GUCY2C CAR-T cells reduced tumor number and morbidity and improved survival in mice harboring GUCY2C-expressing colorectal cancer metastases. GUCY2C-directed T cell efficacy reflected CAR affinity and surface expression and was achieved without immune-mediated damage to normal tissues in syngeneic mice. These observations highlight the potential for therapeutic translation of GUCY2C-directed CAR-T cells to treat metastatic tumors, without collateral autoimmunity, in patients with metastatic colorectal cancer.

  12. Excess breast cancer risk in first degree relatives of CHEK2∗1100delC positive familial breast cancer cases

    NARCIS (Netherlands)

    Adank, Muriel A.; Verhoef, Senno; Oldenburg, Rogier A.; Schmidt, Marjanka K.; Hooning, Maartje J.; Martens, John W. M.; Broeks, Annegien; Rookus, Matti; Waisfisz, Quinten; Witte, Birgit I.; Jonker, Marianne A.; Meijers-Heijboer, Hanne

    2013-01-01

    The CHEK2∗1100delC mutation confers a relative risk of two for breast cancer (BC) in the general population. This study aims to explore the excess cancer risk due to the CHEK2∗1100delC mutation within a familial non-BRCA1/2 breast cancer setting. Cancer incidences were compared between first degree

  13. Short-chain C6 ceramide sensitizes AT406-induced anti-pancreatic cancer cell activity

    International Nuclear Information System (INIS)

    Zhao, Xiaoguang; Sun, Baoyou; Zhang, Jingjing; Zhang, Ruishen; Zhang, Qing

    2016-01-01

    Our previous study has shown that AT406, a first-in-class small molecular antagonist of IAPs (inhibitor of apoptosis proteins), inhibits pancreatic cancer cell proliferation in vitro and in vivo. The aim of this research is to increase AT406's sensitivity by adding short-chain C6 ceramide. We show that co-treatment of C6 ceramide dramatically potentiated AT406-induced caspase/apoptosis activation and cytotoxicity in established (Panc-1 and Mia-PaCa-2 lines) and primary human pancreatic cancer cells. Reversely, caspase inhibitors largely attenuated C6 ceramide plus AT406-induced above cancer cell death. Molecularly, C6 ceramide downregulated Bcl-2 to increase AT406's sensitivity in pancreatic cancer cells. Intriguingly, C6 ceramide-mediated AT406 sensitization was nullified with Bcl-2 shRNA knockdown or pretreatment of the Bcl-2 inhibitor ABT-737. In vivo, liposomal C6 ceramide plus AT406 co-administration dramatically inhibited Panc-1 xenograft tumor growth in severe combined immunodeficient (SCID) mice. The combined anti-tumor activity was significantly more potent than either single treatment. Expressions of IAPs (cIAP1/XIAP) and Bcl-2 were downregulated in Panc-1 xenografts with the co-administration. Together, we demonstrate that C6 ceramide sensitizes AT406-mediated anti-pancreatic cancer cell activity possibly via downregulating Bcl-2. - Highlights: • C6 ceramide dramatically potentiates AT406-induced pancreatic cancer cell death. • C6 ceramide facilitates AT406-induced pancreatic cancer cell apoptosis. • C6 ceramide downregulates Bcl-2 to increase AT406's sensitivity in pancreatic cancer cells. • Liposomal C6 ceramide enhances AT406-induced anti-pancreatic cancer activity in vivo.

  14. Follicular thyroid cancer avid on C-11 Methionine PET/CT

    OpenAIRE

    Jochumsen, Mads Ryø; Iversen, Peter; Arveschoug, Anne Kirstine

    2018-01-01

    Summary A case of follicular thyroid cancer with intense focal Methionine uptake on 11C-Methionine PET/CT is reported here. The use of 11C-Methionine PET in differentiated thyroid cancer is currently being investigated as a surrogate tracer compared to the more widely used 18F-FDG PET. This case illustrates the potential incremental value of this modality, not only in the localizing of parathyroid adenoma, but also indicating that 11C-Methionine PET might have a potential of increasing the pr...

  15. c-Myc-Dependent Cell Competition in Human Cancer Cells.

    Science.gov (United States)

    Patel, Manish S; Shah, Heta S; Shrivastava, Neeta

    2017-07-01

    Cell Competition is an interaction between cells for existence in heterogeneous cell populations of multicellular organisms. This phenomenon is involved in initiation and progression of cancer where heterogeneous cell populations compete directly or indirectly for the survival of the fittest based on differential gene expression. In Drosophila, cells having lower dMyc expression are eliminated by cell competition through apoptosis when present in the milieu of cells having higher dMyc expression. Thus, we designed a study to develop c-Myc (human homolog) dependent in vitro cell competition model of human cancer cells. Cells with higher c-Myc were transfected with c-myc shRNA to prepare cells with lower c-Myc and then co-cultured with the same type of cells having a higher c-Myc in equal ratio. Cells with lower c-Myc showed a significant decrease in numbers when compared with higher c-Myc cells, suggesting "loser" and "winner" status of cells, respectively. During microscopy, engulfment of loser cells by winner cells was observed with higher expression of JNK in loser cells. Furthermore, elimination of loser cells was prevented significantly, when co-cultured cells were treated with the JNK (apoptosis) inhibitor. Above results indicate elimination of loser cells in the presence of winner cells by c-Myc-dependent mechanisms of cell competition in human cancer cells. This could be an important mechanism in human tumors where normal cells are eliminated by c-Myc-overexpressed tumor cells. J. Cell. Biochem. 118: 1782-1791, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  16. C-type natriuretic peptide in prostate cancer

    DEFF Research Database (Denmark)

    Nielsen, Soeren Junge; Iversen, Peter; Rehfeld, Jens F.

    2009-01-01

    C-type natriuretic peptide (CNP) is expressed in the male reproductive organs in pigs. To examine whether the human prostate also expresses the CNP gene, we measured CNP and N-terminal proCNP in prostate cancer tissue extracts and performed immunohistochemical biopsy staining. Additionally, pro......CNP-derived peptides were quantitated in plasma from patients with prostate cancer. Blood was collected from healthy controls and patients before surgery for localized prostate cancer. Tissue extracts were prepared from tissue biopsies obtained from radical prostatectomy surgery. N-terminal proCNP, proCNP (1......-50) and CNP were measured in plasma and tissue extracts. Biopsies were stained for CNP-22 and N-terminal proCNP. Tissue extracts from human prostate cancer contained mostly N-terminal proCNP [median 5.3 pmol/g tissue (range 1.0-12.9)] and less CNP [0.14 pmol/g tissue (0.01-1.34)]. Immunohistochemistry...

  17. Use of Strontium Chloride (89Sr) in evaluation of painful bone metastases arising from carcinoma of prostate gland

    International Nuclear Information System (INIS)

    Mahapatra, G.N.; Shetty, Jayarama K.; More, M.

    2004-01-01

    Full text: Bone metastases that develop in patients with advanced prostatic cancer often cause deep, unremitting pain adversely affecting quality of life, pathologic fracture, immobility, anxiety and depression. Currently, a number of therapies specifically targeted for the treatment of pain from bone metastases are available. These include analgesics, chemotherapy, hormonal therapy, surgery, external beam radiation and systemically administered radiopharmaceuticals. Strontium Chloride (89Sr - Metastron) injection has been used as systemically administered radio therapeutic agent for the palliation of osteoblastic skeletal metastases. It imitates the biodistribution of calcium invivo and is avidly taken up by bony metastases. Twenty-five known prostatic cancer patients with painful bone metastases were assessed following a single injection of 89Sr (2.0 MBq / Kg body weight). Six patients (24%) showed dramatic improvement, 9 patients (36%) have substantial improvement, 5 patients (20%) have some improvements while 5 patients (20%) did not have any improvement. These improvements were assessed in various scoring rates such as improvement in the intensity of pain, fall in the total and free PSA titre, regression in the demonstrated area of metastases in bone scan. The last group of 5 patients who do not show any improvement were also tried with second injection of 89Sr. These patients were followed-up with measurement of total platelets count, differential cell count (DC) and total leucocyte count. Two patients have moderate improvement in the pain relief and rest three patients were refractory to the multiple schedules of injection. We conclude that 89Sr has a significant effect in improving palliation of the distressing symptoms associated with prostate cancer as against the major drawback of external beam radiotherapy limits to the number of sites that can be treated at a time or recurrence at the treated site or new areas of bony pain requiring several hospital

  18. Thymosin beta 10 Prompted the VEGF-C Expression in Lung Cancer Cell

    Directory of Open Access Journals (Sweden)

    Zixuan LI

    2014-05-01

    Full Text Available Background and objective Our previous study found that thymosin β10 overexpressed in lung cancer and positively correlated with differentiation, lymph node metastasis and stage of lung cancer. In this reasearch we aim to study the effects and mechanism of exogenous human recombinant Tβ10 on the expression of VEGF-C on non-small cell lung cancer. Methods After SPC, A549 and LK2 cells were treated with 100 ng/mL recombinant human Tβ10, the mRNA level of VEGF-C were detected by RT-PCR. The mean while the protein expression of VEGF-C, P-AKT and AKT were determined by Western blot assay. Results Exogenous recombinant human Tβ10 were significantly promote the expression levels of VEGF-C mRNA and protein while promoting the phosphorylation of AKT. Exogenous Tβ10 can promote the expression of VEGF-C mRNA and protein in lung cancer cell lines A549 and LK2 (P<0.05, and this effect can be inhibited by use AKT inhibitor LY294002 (P<0.05. Conclusion Tβ10 human recombinant proteins can promote the expression of VEGF-C by activating AKT phosphorylation in lung cancer cell lines.

  19. DNA methylation regulates expression of VEGF-C, and S-adenosylmethionine is effective for VEGF-C methylation and for inhibiting cancer growth

    Energy Technology Data Exchange (ETDEWEB)

    Da, M.X. [Department of Surgical Oncology, Gansu Provincial Hospital, Lanzhou (China); Zhang, Y.B. [Department of Surgery, Ningxia Medical University, Yinchuan (China); Yao, J.B. [Department of Surgical Oncology, Gansu Provincial Hospital, Lanzhou (China); Duan, Y.X. [Department of Surgery, Ningxia Medical University, Yinchuan (China)

    2014-09-30

    DNA hypomethylation may activate oncogene transcription, thus promoting carcinogenesis and tumor development. S-adenosylmethionine (SAM) is a methyl donor in numerous methylation reactions and acts as an inhibitor of intracellular demethylase activity, which results in hypermethylation of DNA. The main objectives of this study were to determine whether DNA hypomethylation correlated with vascular endothelial growth factor-C (VEGF-C) expression, and the effect of SAM on VEGF-C methylation and gastric cancer growth inhibition. VEGF-C expression was assayed by Western blotting and RT-qPCR in gastric cancer cells, and by immunohistochemistry in tumor xenografts. VEGF-C methylation was assayed by bisulfite DNA sequencing. The effect of SAM on cell apoptosis was assayed by flow cytometry analyses and its effect on cancer growth was assessed in nude mice. The VEGF-C promoters of MGC-803, BGC-823, and SGC-7901 gastric cancer cells, which normally express VEGF-C, were nearly unmethylated. After SAM treatment, the VEGF-C promoters in these cells were highly methylated and VEGF-C expression was downregulated. SAM also significantly inhibited tumor growth in vitro and in vivo. DNA methylation regulates expression of VEGF-C. SAM can effectively induce VEGF-C methylation, reduce the expression of VEGF-C, and inhibit tumor growth. SAM has potential as a drug therapy to silence oncogenes and block the progression of gastric cancer.

  20. Investigation of cAMP microdomains as a path to novel cancer diagnostics.

    Science.gov (United States)

    Desman, Garrett; Waintraub, Caren; Zippin, Jonathan H

    2014-12-01

    Understanding of cAMP signaling has greatly improved over the past decade. The advent of live cell imaging techniques and more specific pharmacologic modulators has led to an improved understanding of the intricacies by which cAMP is able to modulate such a wide variety of cellular pathways. It is now appreciated that cAMP is able to activate multiple effector proteins at distinct areas in the cell leading to the activation of very different downstream targets. The investigation of signaling proteins in cancer is a common route to the development of diagnostic tools, prognostic tools, and/or therapeutic targets, and in this review we highlight how investigation of cAMP signaling microdomains driven by the soluble adenylyl cyclase in different cancers has led to the development of a novel cancer biomarker. Antibodies directed against the soluble adenylyl cyclase (sAC) are highly specific markers for melanoma especially for lentigo maligna melanoma and are being described as "second generation" cancer diagnostics, which are diagnostics that determine the 'state' of a cell and not just identify the cell type. Due to the wide presence of cAMP signaling pathways in cancer, we predict that further investigation of both sAC and other cAMP microdomains will lead to additional cancer biomarkers. This article is part of a Special Issue entitled: The role of soluble adenylyl cyclase in health and disease. Copyright © 2014 Elsevier B.V. All rights reserved.

  1. 14 CFR 33.89 - Operation test.

    Science.gov (United States)

    2010-01-01

    ... 14 Aeronautics and Space 1 2010-01-01 2010-01-01 false Operation test. 33.89 Section 33.89... STANDARDS: AIRCRAFT ENGINES Block Tests; Turbine Aircraft Engines § 33.89 Operation test. (a) The operation test must include testing found necessary by the Administrator to demonstrate— (1) Starting, idling...

  2. TU-F-12A-01: Quantitative Non-Linear Compartment Modeling of 89Zr- and 124I- Labeled J591 Monoclonal Antibody Kinetics Using Serial Non-Invasive Positron Emission Tomography Imaging in a Pre-Clinical Human Prostate Cancer Mouse Model

    Energy Technology Data Exchange (ETDEWEB)

    Fung, EK; Cheal, SM; Chalasani, S; Fareedy, SB; Punzalan, B; Humm, JL; Osborne, JR; Larson, SM; Zanzonico, PB [Memorial Sloan Kettering Cancer Center, New York, NY (United States); Otto, B; Bander, NH [Weill Cornell Medical College, New York, NY (United States)

    2014-06-15

    Purpose: To examine the binding kinetics of human IgG monoclonal antibody J591 which targets prostate-specific membrane antigen (PSMA) in a pre-clinical mouse cancer model using quantitative PET compartmental analysis of two radiolabeled variants. Methods: PSMA is expressed in normal human prostate, and becomes highly upregulated in prostate cancer, making it a promising therapeutic target. Two forms of J591, radiolabeled with either {sup 89}Zr or {sup 124}I, were prepared. {sup 89}Zr is a radiometal that becomes trapped in the cell upon internalization by the antigen-antibody complex, while radioiodine leaves the cell. Mice with prostate cancer xenografts underwent non-invasive serial imaging on a Focus 120 microPET up to 144 hours post-injection of J591. A non-linear compartmental model describing the binding and internalization of antibody in tumor xenograft was developed and applied to the PET-derived time-activity curves. The antibody-antigen association rate constant (ka), total amount of antigen per gram tumor (Ag-total), internalization rate of antibody-antigen complex, and efflux rate of radioisotope from tumor were fitted using the model. The surface-bound and the internalized activity were also estimated. Results: Values for ka, Ag-total, and internalization rate were found to be similar regardless of radiolabel payload used. The efflux rate, however, was ∼ 9-fold higher for {sup 124}I-J591 than for {sup 89}Zr-J591. Time-dependent surface-bound and internalized radiotracer activity were similar for both radiolabels at early times post-injection, but clearly differed beyond 24 hours. Conclusion: Binding and internalization of J591 to PSMA-expressing tumor xenografts were similar when radiolabeled with either {sup 89}Zr or {sup 124}I payload. The difference in efflux of radioactivity from tumor may be attributable to differential biological fate intracellularly of the radioisotopes. This has great significance for radioimmunotherapy and antibody

  3. Imaging the L-type amino acid transporter-1 (LAT1 with Zr-89 immunoPET.

    Directory of Open Access Journals (Sweden)

    Oluwatayo F Ikotun

    Full Text Available The L-type amino acid transporter-1 (LAT1, SLC7A5 is upregulated in a wide range of human cancers, positively correlated with the biological aggressiveness of tumors, and a promising target for both imaging and therapy. Radiolabeled amino acids such as O-(2-[(18F]fluoroethyl-L-tyrosine (FET that are transport substrates for system L amino acid transporters including LAT1 have met limited success for oncologic imaging outside of the brain, and thus new strategies are needed for imaging LAT1 in systemic cancers. Here, we describe the development and biological evaluation of a novel zirconium-89 labeled antibody, [(89Zr]DFO-Ab2, targeting the extracellular domain of LAT1 in a preclinical model of colorectal cancer. This tracer demonstrated specificity for LAT1 in vitro and in vivo with excellent tumor imaging properties in mice with xenograft tumors. PET imaging studies showed high tumor uptake, with optimal tumor-to-non target contrast achieved at 7 days post administration. Biodistribution studies demonstrated tumor uptake of 10.5 ± 1.8 percent injected dose per gram (%ID/g at 7 days with a tumor to muscle ratio of 13 to 1. In contrast, the peak tumor uptake of the radiolabeled amino acid [(18F]FET was 4.4 ± 0.5 %ID/g at 30 min after injection with a tumor to muscle ratio of 1.4 to 1. Blocking studies with unlabeled anti-LAT1 antibody demonstrated a 55% reduction of [(89Zr]DFO-Ab2 accumulation in the tumor at 7 days. These results are the first report of direct PET imaging of LAT1 and demonstrate the potential of immunoPET agents for imaging specific amino acid transporters.

  4. Estadiamento inicial dos casos de câncer de mama e colo do útero em mulheres brasileiras Initial staging of breast and cervical cancer in Brazilian women

    Directory of Open Access Journals (Sweden)

    Luiz Claudio Santos Thuler

    2005-11-01

    nas regiões onde estes hospitais estão localizados houve melhora na detecção precoce destes tipos de câncer.PURPOSE: to analyze time trends in the clinical staging at the moment of diagnosis in patients with breast and cervix cancer based on data produced by the Brazilian Public Health System (SUS. METHODS: in the first part of this study we identified the published documents describing clinical staging of patients at the moment of diagnosis. Considering their scarcity and poor representativity we conducted the second part of this study through an active search for information. A form was sent via regular mail to all cancer centers in the country (n=173 requesting information about the tumor site and stage at diagnosis by year, in the period of 1995-2002. The statistical analysis was performed using the "R" statistical package. The results are reported as percentage and boxplots. RESULTS: in the first part of the study (1990-1994 we described data from 18 hospitals concerning 7,458 patients with breast cancer and 7,216 patients with cervix cancer. The median of the percentage of cancers diagnosed at an advanced stage (stages III or IV was 52.6 and 56.8%, respectively. In the second part of the study (1995-2002 data were collected from 89 cancer hospitals and 7 chemotherapy or radiotherapy clinics. There was a total of 43,442 cases of breast cancer and 29,263 of cervix cancer. The response rate based on the potential contact list was 55%. The median percentage of patients in advanced stage was 45.3% for breast cancer and 42.5% for cervix cancer. CONCLUSIONS: few studies have examined the time trends in staging of cancer at diagnosis in Brazilian hospitals. Data obtained from Hospital Cancer Registries showed that in the last decade there was a reduction in the percentage of cervix and breast cancer at the advanced stage. This reduction can be due to an improvement in early detection of these cancers.

  5. 7 CFR 301.89-1 - Definitions.

    Science.gov (United States)

    2010-01-01

    ... 7 Agriculture 5 2010-01-01 2010-01-01 false Definitions. 301.89-1 Section 301.89-1 Agriculture..., DEPARTMENT OF AGRICULTURE DOMESTIC QUARANTINE NOTICES Karnal Bunt § 301.89-1 Definitions. Actual price... part) for or capable of propagation, including a tree, a tissue culture, a plantlet culture, pollen, a...

  6. 49 CFR 89.45 - Department determination.

    Science.gov (United States)

    2010-10-01

    ... 49 Transportation 1 2010-10-01 2010-10-01 false Department determination. 89.45 Section 89.45... Referral of Debts to IRS for Tax Refund Offset § 89.45 Department determination. (a) Following review of... supporting rationale. (b) If the Department either sustains or amends its determination, it shall notify the...

  7. 7 CFR 993.89 - Effective time.

    Science.gov (United States)

    2010-01-01

    ... 7 Agriculture 8 2010-01-01 2010-01-01 false Effective time. 993.89 Section 993.89 Agriculture... Order Regulating Handling Miscellaneous Provisions § 993.89 Effective time. The provisions of this subpart, as well as any amendments to this subpart, shall become effective at such time as the Secretary...

  8. 49 CFR 230.89 - Reverse gear.

    Science.gov (United States)

    2010-10-01

    ... 49 Transportation 4 2010-10-01 2010-10-01 false Reverse gear. 230.89 Section 230.89 Transportation... Reversing Gear § 230.89 Reverse gear. (a) General provisions. Reverse gear, reverse levers, and quadrants... quadrant. Proper counterbalance shall be provided for the valve gear. (b) Air-operated power reverse gear...

  9. 7 CFR 160.89 - Medicinal preparations.

    Science.gov (United States)

    2010-01-01

    ... 7 Agriculture 3 2010-01-01 2010-01-01 false Medicinal preparations. 160.89 Section 160.89... STANDARDS FOR NAVAL STORES Sales and Shipments § 160.89 Medicinal preparations. A compound or mixture containing spirits of turpentine or rosin, or both, with other drugs, when sold for medicinal purposes, is...

  10. An investigation of narrow meson resonance production in antiproton-proton and antiproton-neutron interactions at 6.1 and 8.9 GeV/c

    International Nuclear Information System (INIS)

    Azooz, F.; Butterworth, I.; Dornan, P.J.

    1984-04-01

    The authors made a comprehensive search for narrow meson resonance production in reactions of the type p-barN → π +- sub(fast)X and p-barN → psub(fast)(sub(n-bar)sup(p-bar)X at 6.1 and 8.9 GeV.c in a triggered bubble chamber experiment at the SLAC Hybrid Facility. From a study of all accessible inclusive, semi-inclusive and exclusive states, upper limits are given for production of non-strange resonances with width 2 . The authors find two further peaks of statistical significance in excess of 4 standard deviations with masses in the M approx. 2 GeV/c 2 region, and one further multipion peak with mass approx. 1.54 GeV/c 2 . (author)

  11. Why did the breast cancer lymph node status distribution improve in Denmark in the pre-mammography screening period of 1978-1994?

    International Nuclear Information System (INIS)

    Rostgaard, Klaus; Lynge, Elsebeth; Vaeth, Michael; Rootzen, Helle

    2010-01-01

    Background. Danish breast cancer patients diagnosed in 1978-1994 experienced a trend over time towards a more favourable distribution of lymph node status at time of diagnosis, which was not due to mammography screening. We investigated how this trend could be explained by patient characteristics at diagnosis: age (biological processes), calendar period (e.g. environmental changes), birth cohort (living conditions over a life time), post-menopausal status (a predictor of less favourable nodal status), and tumour diameter (a marker of detection time). Material and methods. The data set consisted of 22 955 patients aged 30-69 years at time of diagnosis with known lymph node status, known tumour diameter, known menopausal status, and clinically detected tumours, available from the Danish Breast Cancer Cooperative Group (DBCG). Age, period, cohort, menopausal status, and tumour diameter were used as predictors in generalised linear models with either node-positive status (at least one of the excised lymph nodes being tumour-positive) or severely node-positive status (at least half of the excised lymph nodes being tumour-positive) as outcomes. Lymph node status was assessed both empirically and estimated using an EM algorithm in order to reduce misclassification. Results and discussion. We found that the improved lymph node status distribution was most likely a period effect due to a combination of earlier detection of clinical tumours, explaining most of the trend in node-positive breast cancer and half of the trend in severely node-positive breast cancer, and some unknown factor affecting lymph node status but not necessarily other tumour characteristics

  12. 21 CFR 1250.89 - Swimming pools.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Swimming pools. 1250.89 Section 1250.89 Food and... SANITATION Sanitation Facilities and Conditions on Vessels § 1250.89 Swimming pools. (a) Fill and draw swimming pools shall not be installed or used. (b) Swimming pools of the recirculation type shall be...

  13. Follicular thyroid cancer avid on C-11 Methionine PET/CT

    Directory of Open Access Journals (Sweden)

    Mads Ryø Jochumsen

    2018-01-01

    Full Text Available A case of follicular thyroid cancer with intense focal Methionine uptake on 11C-Methionine PET/CT is reported here. The use of 11C-Methionine PET in differentiated thyroid cancer is currently being investigated as a surrogate tracer compared to the more widely used 18F-FDG PET. This case illustrates the potential incremental value of this modality, not only in the localizing of parathyroid adenoma, but also indicating that 11C-Methionine PET might have a potential of increasing the pretest likelihood of thyroid malignancy in a cold nodule with highly increased Sestamibi uptake.

  14. Targeting the Anti-Apoptotic Protein c-FLIP for Cancer Therapy

    International Nuclear Information System (INIS)

    Safa, Ahmad R.; Pollok, Karen E.

    2011-01-01

    Cellular FLICE (FADD-like IL-1beta-converting enzyme)-inhibitory protein (c-FLIP) is a major resistance factor and critical anti-apoptotic regulator that inhibits tumor necrosis factor-alpha (TNF-alpha), Fas-L, and TNF-related apoptosis-inducing ligand (TRAIL)-induced apoptosis as well as chemotherapy-triggered apoptosis in malignant cells. c-FLIP is expressed as long (c-FLIP L ), short (c-FLIP S ), and c-FLIP R splice variants in human cells. c-FLIP binds to FADD and/or caspase-8 or -10 in a ligand-dependent and-independent fashion, which in turn prevents death-inducing signaling complex (DISC) formation and subsequent activation of the caspase cascade. Moreover, c-FLIP L and c-FLIP S are known to have multifunctional roles in various signaling pathways, as well as activating and/or upregulating several cytoprotective signaling molecules. Upregulation of c-FLIP has been found in various tumor types, and its downregulation has been shown to restore apoptosis triggered by cytokines and various chemotherapeutic agents. Hence, c-FLIP is an important target for cancer therapy. For example, small interfering RNAs (siRNAs) that specifically knockdown the expression of c-FLIP L in diverse human cancer cell lines augmented TRAIL-induced DISC recruitment and increased the efficacy of chemotherapeutic agents, thereby enhancing effector caspase stimulation and apoptosis. Moreover, small molecules causing degradation of c-FLIP as well as decreasing mRNA and protein levels of c-FLIP L and c-FLIP S splice variants have been found, and efforts are underway to develop other c-FLIP-targeted cancer therapies. This review focuses on (1) the functional role of c-FLIP splice variants in preventing apoptosis and inducing cytokine and drug resistance; (2) the molecular mechanisms that regulate c-FLIP expression; and (3) strategies to inhibit c-FLIP expression and function

  15. CHEK2 (∗) 1100delC Mutation and Risk of Prostate Cancer

    DEFF Research Database (Denmark)

    Hale, Victoria; Weischer, Maren; Park, Jong Y

    2014-01-01

    Although the causes of prostate cancer are largely unknown, previous studies support the role of genetic factors in the development of prostate cancer. CHEK2 plays a critical role in DNA replication by responding to double-stranded breaks. In this review, we provide an overview of the current...... knowledge of the role of a genetic variant, 1100delC, of CHEK2 on prostate cancer risk and discuss the implication for potential translation of this knowledge into clinical practice. Currently, twelve articles that discussed CHEK2 (∗)1100delC and its association with prostate cancer were identified....... Of the twelve prostate cancer studies, five studies had independent data to draw conclusive evidence from. The pooled results of OR and 95% CI were 1.98 (1.23-3.18) for unselected cases and 3.39 (1.78-6.47) for familial cases, indicating that CHEK2 (∗)1100delC mutation is associated with increased risk...

  16. Patient-initiated breast cancer screening

    International Nuclear Information System (INIS)

    Chilcote, W.

    1990-01-01

    This paper reviews the results of a breast cancer screening program sponsored by organizations at workplace or community locations. A comprehensive mobile breast cancer screening program, including education, breast physical examination, and mammography, was provided to 89 local organizations at $50.00 per examination over an 18-month period. The examination was patient initiated, following the ACS screening guidelines. Estimates of eligible women were provided by each organization. A total of 5,030 women at 89 organizations were screened for breast cancer. Approximately 25,727 women were eligible

  17. 9 CFR 89.4 - Watering.

    Science.gov (United States)

    2010-01-01

    ... 9 Animals and Animal Products 1 2010-01-01 2010-01-01 false Watering. 89.4 Section 89.4 Animals and Animal Products ANIMAL AND PLANT HEALTH INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE INTERSTATE TRANSPORTATION OF ANIMALS (INCLUDING POULTRY) AND ANIMAL PRODUCTS STATEMENT OF POLICY UNDER THE TWENTY-EIGHT HOUR...

  18. Imaging HER2 in response to T-DM1 therapy in breast cancer xenografts

    Energy Technology Data Exchange (ETDEWEB)

    Massicano, Adriana Vidal; Aweda, Tolulope; Marqueznostra, Bernadette; El Sayed, Reeta; Beacham, Rebecca; Lapi, Suzanne [University Of Alabama, Birmingham, AL (United States)

    2017-07-01

    days post injection. After baseline imaging, mice received saline (control group) or 15 mg/kg TDM1 (study group) via tail-vein and the imaging schedule was repeated two weeks post T-DM1 injection. The tumor sizes were measured with calipers weekly. Results: Pertuzumab was conjugated to p-NCS-Bz-DFO at a molar ratio of 1:16 and successfully radiolabeled with {sup 89}Zr (20 μCi/μg) with radiochemical yield higher than 95%. {sup 89}Zr-Pertuzumab has shown good stability in NaCl 0.9% at room temperature and at 4 °C as well in human serum and PBS at 37 °C. Two weeks post T-DM1 therapy, the tumor volume in control group increased in 219% whereas, in the study group, the tumors decreased 48% in volume. The {sup 18}F-FDG images showed non-specific uptake in heart and brown fat with relatively little tumor uptake. In contrast, {sup 89}Zr-Pertuzumab images showed more specificity in vivo with good tumor delineation which lead to a clear visualization of changes in tumors size after T-DM1 therapy. Conclusions: {sup 89}Zr-Pertuzumab may provide a novel imaging probe for monitoring the response of breast cancer patients to T-DM1 therapy. (author)

  19. Pairwise comparison of 89Zr- and 124I-labeled cG250 based on positron emission tomography imaging and nonlinear immunokinetic modeling: in vivo carbonic anhydrase IX receptor binding and internalization in mouse xenografts of clear-cell renal cell carcinoma

    International Nuclear Information System (INIS)

    Cheal, Sarah M.; Punzalan, Blesida; Doran, Michael G.; Osborne, Joseph R.; Evans, Michael J.; Lewis, Jason S.; Zanzonico, Pat; Larson, Steven M.

    2014-01-01

    The PET tracer, 124 I-cG250, directed against carbonic anhydrase IX (CAIX) shows promise for presurgical diagnosis of clear-cell renal cell carcinoma (ccRCC) (Divgi et al. in Lancet Oncol 8:304-310, 2007; Divgi et al. in J Clin Oncol 31:187-194, 2013). The radiometal 89 Zr, however, may offer advantages as a surrogate PET nuclide over 124 I in terms of greater tumor uptake and retention (Rice et al. in Semin Nucl Med 41:265-282, 2011). We have developed a nonlinear immunokinetic model to facilitate a quantitative comparison of absolute uptake and antibody turnover between 124 I-cG250 and 89 Zr-cG250 using a human ccRCC xenograft tumor model in mice. We believe that this unique model better relates quantitative imaging data to the salient biological features of tumor antibody-antigen binding and turnover. We conducted experiments with 89 Zr-cG250 and 124 I-cG250 using a human ccRCC cell line (SK-RC-38) to characterize the binding affinity and internalization kinetics of the two tracers in vitro. Serial PET imaging was performed in mice bearing subcutaneous ccRCC tumors to simultaneously detect and quantify time-dependent tumor uptake in vivo. Using the known specific activities of the two tracers, the equilibrium rates of antibody internalization and turnover in the tumors were derived from the PET images using nonlinear compartmental modeling. The two tracers demonstrated virtually identical tumor cell binding and internalization but showed markedly different retentions in vitro. Superior PET images were obtained using 89 Zr-cG250, owing to the more prolonged trapping of the radiolabel in the tumor and simultaneous washout from normal tissues. Estimates of cG250/CAIX complex turnover were 1.35 - 5.51 x 10 12 molecules per hour per gram of tumor (20 % of receptors internalized per hour), and the ratio of 124 I/ 89 Zr atoms released per unit time by tumor was 17.5. Pairwise evaluation of 89 Zr-cG250 and 124 I-cG250 provided the basis for a nonlinear immunokinetic

  20. MicroRNA-128 suppresses paclitaxel-resistant lung cancer by inhibiting MUC1-C and BMI-1 in cancer stem cells.

    Science.gov (United States)

    Koh, Hyebin; Park, Hyeri; Chandimali, Nisansala; Huynh, Do Luong; Zhang, Jiao Jiao; Ghosh, Mrinmoy; Gera, Meeta; Kim, Nameun; Bak, Yesol; Yoon, Do-Young; Park, Yang Ho; Kwon, Taeho; Jeong, Dong Kee

    2017-12-15

    The existence of cancer stem cells (CSCs) is the main reason for failure of cancer treatment caused by drug resistance. Therefore, eradicating cancers by targeting CSCs remains a significant challenge. In the present study, because of the important role of BMI-1 proto-oncogene, polycomb ring finger (BMI-1) and C-terminal Mucin1 (MUC1-C) in tumor growth and maintenance of CSCs, we aimed to confirm that microRNA miR-128, as an inhibitor of BMI-1 and MUC1-C, could effectively suppress paclitaxel (PTX)-resistant lung cancer stem cells. We showed that CSCs have significantly higher expression levels of BMI-1, MUC1-C, stemness proteins, signaling factors, and higher malignancy compared with normal tumor cells. After transfection with miR-128, the BMI-1 and MUC1-C levels in CSCs were suppressed. When miR-128 was stably expressed in PTX-resistant lung cancer stem cells, the cells showed decreased proliferation, metastasis, self-renewal, migration, invasive ability, clonogenicity, and tumorigenicity in vitro and in vivo and increased apoptosis compared with miR-NC (negative control) CSCs. Furthermore, miR-128 effectively decreased the levels of β-catenin and intracellular signaling pathway-related factors in CSCs. MiR-128 also decreased the luciferase activity of MUC1 reporter constructs and reduced the levels of transmembrane MUC1-C and BMI-1. These results suggested miR-128 as an attractive therapeutic strategy for PTX-resistant lung cancer via inhibition of BMI-1 and MUC1-C.

  1. Therapeutic radiation at a young age is linked to secondary thyroid cancer. The Late Effects Study Group

    International Nuclear Information System (INIS)

    Tucker, M.A.; Jones, P.H.; Boice, J.D. Jr.; Robison, L.L.; Stone, B.J.; Stovall, M.; Jenkin, R.D.; Lubin, J.H.; Baum, E.S.; Siegel, S.E.

    1991-01-01

    We estimated the risk of thyroid cancer among 9170 patients who had survived 2 or more years after the diagnosis of a cancer in childhood. As compared with the general population, patients had a 53-fold increased risk (95% confidence interval, 34-80). Risk increased significantly with time since treatment for the initial cancer (P = 0.03). Detailed treatment data were obtained for 23 cases and 89 matched controls from the childhood cancer cohort. Sixty-eight % of the thyroid cancers arose within the field of radiation. Radiation doses to the thyroid of greater than 200 cGy were associated with a 13-fold increased risk (95% confidence interval, 1.7-104). The risk of thyroid cancer rose with increasing dose (P less than 0.001), but this was derived almost entirely from the increase from less than 200 to greater than 200 cGy. The risk of thyroid cancer did not decrease, however, at radiation doses as high as 6000 cGy

  2. High-Risk Premenopausal Luminal A Breast Cancer Patients Derive no Benefit from Adjuvant Cyclophosphamide-based Chemotherapy: Results from the DBCG77B Clinical Trial.

    Science.gov (United States)

    Nielsen, Torsten O; Jensen, Maj-Brit; Burugu, Samantha; Gao, Dongxia; Jørgensen, Charlotte L Tykjaer; Balslev, Eva; Ejlertsen, Bent

    2017-02-15

    Purpose: Luminal A breast cancers have better prognosis than other molecular subtypes. Luminal A cancers may also be insensitive to adjuvant chemotherapy, although there is little high-level evidence to confirm this concept. The primary hypothesis in this formal prospective-retrospective analysis was to assess interaction between subtype (Luminal A vs. other) and treatment (chemotherapy vs. not) for the primary endpoint (10-year invasive disease-free survival) of a breast cancer trial randomizing women to adjuvant chemotherapy, analyzed in multivariate Cox proportional hazards models using the Wald interaction test. Experimental Design: The Danish Breast Cancer Cooperative Group 77B clinical trial randomized 1,072 premenopausal women to no systematic treatment (control), levamisole, cyclophosphamide, or cyclophosphamide-methotrexate-fluorouracil arms. All arms included radiotherapy but no endocrine therapy. Researchers with no access to clinical data performed intrinsic subtype analysis on tissue microarrays using published immunohistochemical methods based on estrogen receptor, progesterone receptor, HER2, Ki67, and basal markers. Results: Patients ( n = 709) had tissue available; chemotherapy benefit in these patients was similar to the original trial (HR, 0.56). Immunohistochemistry classified 165 as Luminal A, 319 Luminal B, 58 HER2-enriched, and 82 core basal (among 91 triple-negative). Patients with Luminal A breast tumors did not benefit from chemotherapy [HR, 1.06; 95% confidence interval (CI), 0.53-2.14; P = 0.86], whereas patients with non-luminal A subtypes did (HR, 0.50; 95% CI, 0.38-0.66; P benefit from adjuvant cyclophosphamide-based chemotherapy. Clin Cancer Res; 23(4); 946-53. ©2016 AACR . ©2016 American Association for Cancer Research.

  3. Intensity Modulated Radiation Therapy Dose Painting for Localized Prostate Cancer Using 11C-choline Positron Emission Tomography Scans

    International Nuclear Information System (INIS)

    Chang, Joe H.; Lim Joon, Daryl; Lee, Sze Ting; Gong, Sylvia J.; Anderson, Nigel J.; Scott, Andrew M.; Davis, Ian D.; Clouston, David; Bolton, Damien; Hamilton, Christopher S.; Khoo, Vincent

    2012-01-01

    Purpose: To demonstrate the technical feasibility of intensity modulated radiation therapy (IMRT) dose painting using 11 C-choline positron emission tomography PET scans in patients with localized prostate cancer. Methods and Materials: This was an RT planning study of 8 patients with prostate cancer who had 11 C-choline PET scans prior to radical prostatectomy. Two contours were semiautomatically generated on the basis of the PET scans for each patient: 60% and 70% of the maximum standardized uptake values (SUV 60% and SUV 70% ). Three IMRT plans were generated for each patient: PLAN 78 , which consisted of whole-prostate radiation therapy to 78 Gy; PLAN 78-90 , which consisted of whole-prostate RT to 78 Gy, a boost to the SUV 60% to 84 Gy, and a further boost to the SUV 70% to 90 Gy; and PLAN 72-90 , which consisted of whole-prostate RT to 72 Gy, a boost to the SUV 60% to 84 Gy, and a further boost to the SUV 70% to 90 Gy. The feasibility of these plans was judged by their ability to reach prescription doses while adhering to published dose constraints. Tumor control probabilities based on PET scan-defined volumes (TCP PET ) and on prostatectomy-defined volumes (TCP path ), and rectal normal tissue complication probabilities (NTCP) were compared between the plans. Results: All plans for all patients reached prescription doses while adhering to dose constraints. TCP PET values for PLAN 78 , PLAN 78-90 , and PLAN 72-90 were 65%, 97%, and 96%, respectively. TCP path values were 71%, 97%, and 89%, respectively. Both PLAN 78-90 and PLAN 72-90 had significantly higher TCP PET (P=.002 and .001) and TCP path (P 78 . PLAN 78-90 and PLAN 72-90 were not significantly different in terms of TCP PET or TCP path . There were no significant differences in rectal NTCPs between the 3 plans. Conclusions: IMRT dose painting for localized prostate cancer using 11 C-choline PET scans is technically feasible. Dose painting results in higher TCPs without higher NTCPs.

  4. RAD51C germline mutations in breast and ovarian cancer cases from high-risk families.

    Directory of Open Access Journals (Sweden)

    Jessica Clague

    Full Text Available BRCA1 and BRCA2 are the most well-known breast cancer susceptibility genes. Additional genes involved in DNA repair have been identified as predisposing to breast cancer. One such gene, RAD51C, is essential for homologous recombination repair. Several likely pathogenic RAD51C mutations have been identified in BRCA1- and BRCA2-negative breast and ovarian cancer families. We performed complete sequencing of RAD51C in germline DNA of 286 female breast and/or ovarian cancer cases with a family history of breast and ovarian cancers, who had previously tested negative for mutations in BRCA1 and BRCA2. We screened 133 breast cancer cases, 119 ovarian cancer cases, and 34 with both breast and ovarian cancers. Fifteen DNA sequence variants were identified; including four intronic, one 5' UTR, one promoter, three synonymous, and six non-synonymous variants. None were truncating. The in-silico SIFT and Polyphen programs were used to predict possible pathogenicity of the six non-synonomous variants based on sequence conservation. G153D and T287A were predicted to be likely pathogenic. Two additional variants, A126T and R214C alter amino acids in important domains of the protein such that they could be pathogenic. Two-hybrid screening and immunoblot analyses were performed to assess the functionality of these four non-synonomous variants in yeast. The RAD51C-G153D protein displayed no detectable interaction with either XRCC3 or RAD51B, and RAD51C-R214C displayed significantly decreased interaction with both XRCC3 and RAD51B (p<0.001. Immunoblots of RAD51C-Gal4 activation domain fusion peptides showed protein levels of RAD51C-G153D and RAD51C-R214C that were 50% and 60% of the wild-type, respectively. Based on these data, the RAD51C-G153D variant is likely to be pathogenic, while the RAD51C- R214C variant is hypomorphic of uncertain pathogenicity. These results provide further support that RAD51C is a rare breast and ovarian cancer susceptibility gene.

  5. Hepatitis C virus infection and risk of cancer: a population-based cohort study

    DEFF Research Database (Denmark)

    Omland, Lars Haukali Hvass; Farkas, Dora Körmendiné; Jepsen, Peter

    2010-01-01

    Hepatitis C virus (HCV) infection is associated with an increased risk of primary liver cancer; however, 5- and 10-year risk estimates are needed. The association of HCV with non-Hodgkin lymphoma (NHL) is uncertain and the association with other cancers is unknown.......Hepatitis C virus (HCV) infection is associated with an increased risk of primary liver cancer; however, 5- and 10-year risk estimates are needed. The association of HCV with non-Hodgkin lymphoma (NHL) is uncertain and the association with other cancers is unknown....

  6. Clinical and prognostic value of the C-Met/HGF signaling pathway in cervical cancer.

    Science.gov (United States)

    Boromand, Nadia; Hasanzadeh, Malihe; ShahidSales, Soodabeh; Farazestanian, Marjaneh; Gharib, Masoumeh; Fiuji, Hamid; Behboodi, Negin; Ghobadi, Niloofar; Hassanian, Seyed Mahdi; Ferns, Gordon A; Avan, Amir

    2018-06-01

    Aberrant activation of the HGF/c-Met signalling pathway is reported to be associated with cell proliferation, progression, and metastasis features of several tumor types, including cervical cancer, suggesting that it may be of potential value as a novel therapeutic target. Furthermore, HPV-positive patients had a higher serum level of HGF or c-Met protein, compared with HPV-negative patients. c-Met or HGF overexpression in lesions of cervical cancer is reported to be related to a poorer prognosis, and hence this may be of value as a prognostic and predictive biomarker. Several approaches have been developed for targeting HGF and/or c-Met. One of these is crizotinib (a dual c-Met/ALK inhibitor). This has been approved by FDA for the treatment of lung-cancer. Further investigations are required to evaluate and optimize the use of c-Met inhibitors in cervical cancer or parallel targeting signalling pathway associated/activated via MET/HGF pathway. The main aim of current review was to give an overview of the potential of the c-Met/HGF pathway as a prognostic, or predictive biomarker in cervical cancer. © 2017 Wiley Periodicals, Inc.

  7. Hyperhomocysteinemia, methylenetetrahydrofolate reductase c.677C>T polymorphism and risk of cancer: cross-sectional and prospective studies and meta-analyses of 75,000 cases and 93,000 controls

    DEFF Research Database (Denmark)

    Zacho, Jeppe; Yazdanyar, Shiva; Bojesen, Stig E

    2011-01-01

    from 1.0. However, in meta-analyses odds ratio for MTHFR c.677C>T homozygotes versus noncarriers were 1.07 (95% CI: 1.01-1.12) for any cancer, 1.77 (1.17-2.68) for esophagus cancer, 1.40 (1.19-1.66) for gastric cancer and 0.85 (0.77-0.94) for colorectal cancer. Increased plasma homocysteine levels...... are not associated with an increased age-adjusted risk of any cancer. However, MTHFR c.677C>T homozygosity with lifelong hyperhomocysteinemia and hence hypomethylation associate with increased risk of esophagus and gastric cancer, and with decreased risk of colorectal cancer.......Global DNA hypomethylation associates with development of cancer. DNA hypomethylation also associates with hyperhomocysteinemia and MTHFR c.677C>T homozygosity, both of which may associate with increased risk of cancer. We tested the putative association of hyperhomocysteinemia with cancer...

  8. Development of antibody-based c-Met inhibitors for targeted cancer therapy

    Directory of Open Access Journals (Sweden)

    Lee D

    2015-02-01

    Full Text Available Dongheon Lee, Eun-Sil Sung, Jin-Hyung Ahn, Sungwon An, Jiwon Huh, Weon-Kyoo You Hanwha Chemical R&D Center, Biologics Business Unit, Daejeon, Republic of Korea Abstract: Signaling pathways mediated by receptor tyrosine kinases (RTKs and their ligands play important roles in the development and progression of human cancers, which makes RTK-mediated signaling pathways promising therapeutic targets in the treatment of cancer. Compared with small-molecule compounds, antibody-based therapeutics can more specifically recognize and bind to ligands and RTKs. Several antibody inhibitors of RTK-mediated signaling pathways, such as human epidermal growth factor receptor 2, vascular endothelial growth factor, epidermal growth factor receptor or vascular endothelial growth factor receptor 2, have been developed and are widely used to treat cancer patients. However, since the therapeutic options are still limited in terms of therapeutic efficacy and types of cancers that can be treated, efforts are being made to identify and evaluate novel RTK-mediated signaling pathways as targets for more efficacious cancer treatment. The hepatocyte growth factor/c-Met signaling pathway has come into the spotlight as a promising target for development of potent cancer therapeutic agents. Multiple antibody-based therapeutics targeting hepatocyte growth factor or c-Met are currently in preclinical or clinical development. This review focuses on the development of inhibitors of the hepatocyte growth factor/c-Met signaling pathway for cancer treatment, including critical issues in clinical development and future perspectives for antibody-based therapeutics. Keywords: hepatocyte growth factor, ligands, receptor tyrosine kinase, signaling pathway, therapeutic agent

  9. Half-life measurement of 89Rb

    International Nuclear Information System (INIS)

    Guo Xiaoqing; Yuan Daqing; Xu Lijun; Chen Kesheng; Wu Yongle; Zheng Yanming; Yao Shunhe

    2013-01-01

    89 Rb is an important fission product used for monitoring possible release of fission products from fuel element. The half-life is one of important nuclear parameters. The half-life of 89 Rb was determined using reference source method with two sets of HPGe detectors by place-relay way. In reference source method, the ratio of net full- energy peak areas from the measure nuclide and the reference source was used to avoid the count correction caused by dead time and pileup. For the very short half-life of 89 Rb, the half-life iterative method was used in data analysis and the translation method was used in data unification. Finally, the measured half-life of 89 Rb is (14.41±0.04) min. (authors)

  10. An investigation of narrow meson resonance production in antiproton-proton and antiproton-neutron interactions at 6.1 and 8.9 GeV/c

    International Nuclear Information System (INIS)

    Azooz, F.; Butterworth, I.; Dornan, P.J.; Hall, G.; Stern, R.A.; White, A.P.; Brown, R.C.; Butler, N.; Gopal, G.P.; McPherson, A.; Sekulin, R.L.; Brau, J.E.; Carroll, J.T.; Chaloupka, V.; Cautis, C.V.; Dumont, J.J.; Ericson, R.A.; Field, R.C.; Freytag, D.R.; Grandpeix, J.Y.; Kitagaki, T.; Tanaka, S.; Yuta, H.; Abe, K.; Hasegawa, K.; Yamaguchi, A.; Tamai, K.; Takanashi, H.; Mann, W.A.; Schneps, J.; Wald, H.B.

    1984-01-01

    We have made a comprehensive search for narrow meson resonance production in reactions of the type anti pN->πsub(fast)sup(+-)X and anti pN->psub(fast)X at 6.1 and 8.9 Gev/c in a triggered bubble chamber experiment at the SLAC hybrid facility. From a study of all accessible inclusive, semi-inclusive and exclusive states we give upper limits for production of non-strange resonances with width 2 . In a previous publication [1] we gave evidence for production of a narrow state of mass 2.02 GeV/c 2 , coupled to Nanti N, in our data. In the present study we find two further peaks of statistical significance in excess of 4 standard deviations with masses in the Mproportional2 GeV/c 2 region, and one further multipion peak with mass proportional1.54 GeV/c 2 , all of which merit further experimental investigation. (orig.)

  11. Targeted delivery of miR-200c/DOC to inhibit cancer stem cells and cancer cells by the gelatinases-stimuli nanoparticles.

    Science.gov (United States)

    Liu, Qin; Li, Ru-Tian; Qian, Han-Qing; Wei, Jia; Xie, Li; Shen, Jie; Yang, Mi; Qian, Xiao-Ping; Yu, Li-Xia; Jiang, Xi-Qun; Liu, Bao-Rui

    2013-09-01

    Cancer stem cells (CSCs) are recently discovered as vital obstacles for the successful cancer therapy. Emerging evidences suggest that miR-200c functions as an effective CSCs inhibitor and can restore sensitivity to microtubule-targeting drugs. In the present work, the intelligent gelatinases-stimuli nanoparticles (NPs) was set up to co-deliver miR-200c and docetaxel (DOC) to verify their synergetic effects on inhibition of CSCs and non-CSC cancer cells. After tumor cells were treated with miR-200c NPs, miR-200c and its targeted gene class III beta-tubulin (TUBB3)TUBB3 expression were evaluated. The effects of miR-200c/DOC NPs on tumor cell viability, migration and invasion as well as the expression of E-cadherin and CD44 were studied. The antitumor effects of miR-200c/DOC NPs were compared with DOC NPs in xenograft gastric cancer mice. Moreover, the residual tumors after treatment were subcutaneously seeded into nude mice to further investigate the effective maintenance of NPs. We found that the gelatinases-stimuli NPs facilitated miR-200c into cells, achieving sustained miR-200c expression in tumor cells during 9 days. The miR-200c/DOC NPs significantly enhanced cytotoxicity of DOC, possibly by decreasing TUBB3 level, and reversing EMT. The miR-200c NPs achieved high levels of in vivo accumulation and long retention in gastric cancer xenografts after intravenous administration. The miR-200c/DOC NPs prominently suppressed in vivo tumor growth with elevated miR-200c and E-cadherin levels and down-regulated TUBB3 and CD44 expressions. When the residual tumors after miR-200c/DOC NPs treatment were re-transplanted into nude mice, the tumors demonstrated the slowest growth speed. The miR-200c/DOC NPs may provide a promising modality for co-delivery of nucleic acid and drugs to simultaneously inhibit CSCs and non-CSC cancer cells. Copyright © 2013 Elsevier Ltd. All rights reserved.

  12. MicroRNA-490-5p inhibits proliferation of bladder cancer by targeting c-Fos

    International Nuclear Information System (INIS)

    Li, Shiqi; Xu, Xianglai; Xu, Xin; Hu, Zhenghui; Wu, Jian; Zhu, Yi; Chen, Hong; Mao, Yeqing; Lin, Yiwei; Luo, Jindan; Zheng, Xiangyi; Xie, Liping

    2013-01-01

    Highlights: •We examined the level of miR-490-5p in bladder cancer tissues and three cancer cell lines. •We are the first to show the function of miR-490-5p in bladder cancer. •We demonstrate c-Fos may be a target of miR-490-5p. -- Abstract: MicroRNAs (miRNAs) are non-protein-coding sequences that play a crucial role in tumorigenesis by negatively regulating gene expression. Here, we found that miR-490-5p is down-regulated in human bladder cancer tissue and cell lines compared to normal adjacent tissue and a non-malignant cell line. To better characterize the function of miR-490-5p in bladder cancer, we over-expressed miR-490-5p in bladder cancer cell lines with chemically synthesized mimics. Enforced expression of miR-490-5p in bladder cancer cells significantly inhibited the cell proliferation via G1-phase arrest. Further studies found the decreased c-Fos expression at both mRNA and protein levels and Luciferase reporter assays demonstrated that c-Fos is a direct target of miR-490-5p in bladder cancer. These findings indicate miR-490-5p to be a novel tumor suppressor of bladder cancer cell proliferation through targeting c-Fos

  13. p53 modulates the AMPK inhibitor compound C induced apoptosis in human skin cancer cells

    Energy Technology Data Exchange (ETDEWEB)

    Huang, Shi-Wei [Institute of Biomedical Sciences, National Chung Hsing University, Taichung, Taiwan (China); Wu, Chun-Ying [Division of Gastroenterology and Hepatology, Taichung Veterans General Hospital, Taichung, Taiwan (China); Wang, Yen-Ting [Department of Medical Research and Education, Cheng Hsin General Hospital, Taipei, Taiwan (China); Kao, Jun-Kai [Institute of Biomedical Sciences, National Chung Hsing University, Taichung, Taiwan (China); Department of Pediatrics, Children' s Hospital, Changhua Christian Hospital, Changhua, Taiwan (China); Lin, Chi-Chen; Chang, Chia-Che; Mu, Szu-Wei; Chen, Yu-Yu [Institute of Biomedical Sciences, National Chung Hsing University, Taichung, Taiwan (China); Chiu, Husan-Wen [Institute of Biotechnology, National Cheng-Kung University, Tainan, Taiwan (China); Agricultural Biotechnology Research Center, Academia Sinica, Taipei, Taiwan (China); Chang, Chuan-Hsun [Department of Surgical Oncology, Cheng Hsin General Hospital, Taipei, Taiwan (China); Department of Nutrition Therapy, Cheng Hsin General Hospital, Taipei, Taiwan (China); School of Nutrition and Health Sciences, Taipei Medical University, Taipei, Taiwan (China); Liang, Shu-Mei [Institute of Biotechnology, National Cheng-Kung University, Tainan, Taiwan (China); Agricultural Biotechnology Research Center, Academia Sinica, Taipei, Taiwan (China); Chen, Yi-Ju [Department of Dermatology, Taichung Veterans General Hospital, Taichung, Taiwan (China); Huang, Jau-Ling [Department of Bioscience Technology, Chang Jung Christian University, Tainan, Taiwan (China); Shieh, Jeng-Jer, E-mail: shiehjj@vghtc.gov.tw [Institute of Biomedical Sciences, National Chung Hsing University, Taichung, Taiwan (China); Department of Education and Research, Taichung Veterans General Hospital, Taichung, Taiwan (China)

    2013-02-15

    Compound C, a well-known inhibitor of the intracellular energy sensor AMP-activated protein kinase (AMPK), has been reported to cause apoptotic cell death in myeloma, breast cancer cells and glioma cells. In this study, we have demonstrated that compound C not only induced autophagy in all tested skin cancer cell lines but also caused more apoptosis in p53 wildtype skin cancer cells than in p53-mutant skin cancer cells. Compound C can induce upregulation, phosphorylation and nuclear translocalization of the p53 protein and upregulate expression of p53 target genes in wildtype p53-expressing skin basal cell carcinoma (BCC) cells. The changes of p53 status were dependent on DNA damage which was caused by compound C induced reactive oxygen species (ROS) generation and associated with activated ataxia-telangiectasia mutated (ATM) protein. Using the wildtype p53-expressing BCC cells versus stable p53-knockdown BCC sublines, we present evidence that p53-knockdown cancer cells were much less sensitive to compound C treatment with significant G2/M cell cycle arrest and attenuated the compound C-induced apoptosis but not autophagy. The compound C induced G2/M arrest in p53-knockdown BCC cells was associated with the sustained inactive Tyr15 phosphor-Cdc2 expression. Overall, our results established that compound C-induced apoptosis in skin cancer cells was dependent on the cell's p53 status. - Highlights: ► Compound C caused more apoptosis in p53 wildtype than p53-mutant skin cancer cells. ► Compound C can upregulate p53 expression and induce p53 activation. ► Compound C induced p53 effects were dependent on ROS induced DNA damage pathway. ► p53-knockdown attenuated compound C-induced apoptosis but not autophagy. ► Compound C-induced apoptosis in skin cancer cells was dependent on p53 status.

  14. p53 modulates the AMPK inhibitor compound C induced apoptosis in human skin cancer cells

    International Nuclear Information System (INIS)

    Huang, Shi-Wei; Wu, Chun-Ying; Wang, Yen-Ting; Kao, Jun-Kai; Lin, Chi-Chen; Chang, Chia-Che; Mu, Szu-Wei; Chen, Yu-Yu; Chiu, Husan-Wen; Chang, Chuan-Hsun; Liang, Shu-Mei; Chen, Yi-Ju; Huang, Jau-Ling; Shieh, Jeng-Jer

    2013-01-01

    Compound C, a well-known inhibitor of the intracellular energy sensor AMP-activated protein kinase (AMPK), has been reported to cause apoptotic cell death in myeloma, breast cancer cells and glioma cells. In this study, we have demonstrated that compound C not only induced autophagy in all tested skin cancer cell lines but also caused more apoptosis in p53 wildtype skin cancer cells than in p53-mutant skin cancer cells. Compound C can induce upregulation, phosphorylation and nuclear translocalization of the p53 protein and upregulate expression of p53 target genes in wildtype p53-expressing skin basal cell carcinoma (BCC) cells. The changes of p53 status were dependent on DNA damage which was caused by compound C induced reactive oxygen species (ROS) generation and associated with activated ataxia-telangiectasia mutated (ATM) protein. Using the wildtype p53-expressing BCC cells versus stable p53-knockdown BCC sublines, we present evidence that p53-knockdown cancer cells were much less sensitive to compound C treatment with significant G2/M cell cycle arrest and attenuated the compound C-induced apoptosis but not autophagy. The compound C induced G2/M arrest in p53-knockdown BCC cells was associated with the sustained inactive Tyr15 phosphor-Cdc2 expression. Overall, our results established that compound C-induced apoptosis in skin cancer cells was dependent on the cell's p53 status. - Highlights: ► Compound C caused more apoptosis in p53 wildtype than p53-mutant skin cancer cells. ► Compound C can upregulate p53 expression and induce p53 activation. ► Compound C induced p53 effects were dependent on ROS induced DNA damage pathway. ► p53-knockdown attenuated compound C-induced apoptosis but not autophagy. ► Compound C-induced apoptosis in skin cancer cells was dependent on p53 status

  15. 7 CFR 301.89-2 - Regulated articles.

    Science.gov (United States)

    2010-01-01

    ... 7 Agriculture 5 2010-01-01 2010-01-01 false Regulated articles. 301.89-2 Section 301.89-2... SERVICE, DEPARTMENT OF AGRICULTURE DOMESTIC QUARANTINE NOTICES Karnal Bunt § 301.89-2 Regulated articles. The following are regulated articles: (a) Conveyances, including trucks, railroad cars, and other...

  16. Expression of oncogen c-erbB-2 (neu/HER-2) in human breast cancer

    International Nuclear Information System (INIS)

    Michelin, Severino C.; Mayo, Jose

    2000-01-01

    Breast cancer continues to be one of the leading causes of death from cancer among women and represents the most serious challenge to therapeutic control. Amplification and overexpression of the c-erbB-2 proto-oncogene occurs in as many as 30 % of all breast cancers and has been correlated with lymph node metastasis and poor prognosis in breast cancer patients. This gene know as neu, HER-2 or c-erbB-2 in among those most frequently altered in human cancer. It was first identified as a transforming gene activated in chemically induced rat neuroectodermal tumors. Early critical studies linked changes in erbB-2 expression and gene copy number to several human cancer, notably breast, ovarian and gastric cancer. Owing to its accessible location at the cell surface, erbB-2 is now under intensive scrutiny as a therapeutic target. In this review we will summarize the involvement of the c-erbB-2 gene in tumorigenesis. (author)

  17. Validación de los códigos diagnósticos de cáncer de colon y recto del Conjunto Mínimo Básico de Datos Validation of colorectal cancer diagnostic codes in a hospital administration data set

    Directory of Open Access Journals (Sweden)

    Mirari Márquez Cid

    2006-08-01

    Full Text Available Objetivo: Validar la capacidad del Conjunto Mínimo Básico de Datos (CMBD para detectar casos incidentes de cáncer de colon y recto utilizando como estándar de referencia el Registro de Cáncer de Murcia (RCM y medir la concordancia entre el CMBD y el registro de cáncer en tumores colorrectales. Material y método: Estudio de validación transversal del CMBD del Hospital Virgen de la Arrixaca de Murcia. La población de estudio son los casos incidentes de colon-recto del año 2000 del RCM y los casos del CMBD en el citado hospital para el mismo año con algún código diagnóstico CIE-9 entre 153.0 y 154.1 eliminando reingresos. Durante el proceso se van a realizar 2 análisis: sólo con el diagnóstico principal y con todos los diagnósticos. Se calcula la sensibilidad, la especificidad, el valor predictivo positivo (VPP y negativo (VPN y la concordancia con sus intervalos de confianza (IC del 95%. Resultados: Con sólo el primer diagnóstico, el CMBD detecta el 80% de los casos incidentes de cáncer colorrectal con un VPP del 75%; considerando todos los diagnósticos, detecta el 85% con un VPP del 64%. La concordancia en la codificación es elevada tanto con 3 dígitos (índice kappa del 88% (IC del 95%, 0,79-0,97 en primer diagnóstico, y del 89% (IC del 95%, 0,80-0,97 en todos los diagnósticos como de 4 dígitos (índice kappa del 77% (IC del 95%, 0,68-0,85 en el primer diagnóstico, y del 78% (IC del 95%, 0,70-0,86 en todos diagnósticos en ambos análisis. Conclusiones: El CMBD es una buena fuente para detectar casos incidentes de cáncer al presentar una elevada sensibilidad. La alta concordancia encontrada en las localizaciones tumorales de colon-recto contribuye a consolidar el CMBD como fuente de datos para los registros de cáncer.Objectives: To validate the ability of a hospital administration data set (minimum data set [MDS] to detect incident cases of colorectal cancer using the Murcia Cancer Registry (MCR as the gold standard

  18. Monitoring Cancer Response to Treatment with Hyperpolarized 13C MRS

    DEFF Research Database (Denmark)

    Eldirdiri, Abubakr

    , and the patient is exposed to ionizing radiation. The introduction of hyperpolarized 13C MRS has opened completely new possibilities to study the biochemical changes in disease processes. Numerous 13C-labeled compounds were proposed to interrogate various aspects of cancer cell metabolism. The aim of this study......Monitoring the cancer response to treatment, non-invasively, by medical imaging is a key element in the management of cancer. For patients undergoing treatment, it is crucial to determine responders from non-responders in order to guide treatment decisions. Currently, PET is the most widely used...

  19. Inflammatory lipid sphingosine-1-phosphate upregulates C-reactive protein via C/EBPβ and potentiates breast cancer progression

    NARCIS (Netherlands)

    Kim, E.S.; Cha, Y.; Ham, M.; Jung, J.; Kim, S.G.; Hwang, S.; Kleemann, R.; Moon, A.

    2014-01-01

    A crucial role of the inflammatory lipid sphingosine-1-phosphate (S1P) in breast cancer aggressiveness has been reported. Recent clinical studies have suggested that C-reactive protein (CRP) has a role in breast cancer development. However, limited information is available on the molecular basis for

  20. Metabolic Imaging of Patients with Prostate Cancer Using Hyperpolarized [1-13C]Pyruvate

    Science.gov (United States)

    Nelson, Sarah J.; Kurhanewicz, John; Vigneron, Daniel B.; Larson, Peder E. Z.; Harzstark, Andrea L.; Ferrone, Marcus; van Criekinge, Mark; Chang, Jose W.; Bok, Robert; Park, Ilwoo; Reed, Galen; Carvajal, Lucas; Small, Eric J.; Munster, Pamela; Weinberg, Vivian K.; Ardenkjaer-Larsen, Jan Henrik; Chen, Albert P.; Hurd, Ralph E.; Odegardstuen, Liv-Ingrid; Robb, Fraser J.; Tropp, James; Murray, Jonathan A.

    2014-01-01

    This first-in-man imaging study evaluated the safety and feasibility of hyperpolarized [1-13C]pyruvate as an agent for noninvasively characterizing alterations in tumor metabolism for patients with prostate cancer. Imaging living systems with hyperpolarized agents can result in more than 10,000-fold enhancement in signal relative to conventional magnetic resonance (MR) imaging. When combined with the rapid acquisition of in vivo 13C MR data, it is possible to evaluate the distribution of agents such as [1-13C]pyruvate and its metabolic products lactate, alanine, and bicarbonate in a matter of seconds. Preclinical studies in cancer models have detected elevated levels of hyperpolarized [1-13C]lactate in tumor, with the ratio of [1-13C]lactate/[1-13C]pyruvate being increased in high-grade tumors and decreased after successful treatment. Translation of this technology into humans was achieved by modifying the instrument that generates the hyperpolarized agent, constructing specialized radio frequency coils to detect 13C nuclei, and developing new pulse sequences to efficiently capture the signal. The study population comprised patients with biopsy-proven prostate cancer, with 31 subjects being injected with hyperpolarized [1-13C]pyruvate. The median time to deliver the agent was 66 s, and uptake was observed about 20 s after injection. No dose-limiting toxicities were observed, and the highest dose (0.43 ml/kg of 230 mM agent) gave the best signal-to-noise ratio for hyperpolarized [1-13C]pyruvate. The results were extremely promising in not only confirming the safety of the agent but also showing elevated [1-13C]lactate/[1-13C]pyruvate in regions of biopsy-proven cancer. These findings will be valuable for noninvasive cancer diagnosis and treatment monitoring in future clinical trials. PMID:23946197

  1. 40 CFR 89.406 - Pre-test procedures.

    Science.gov (United States)

    2010-07-01

    ... 40 Protection of Environment 20 2010-07-01 2010-07-01 false Pre-test procedures. 89.406 Section 89.406 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR PROGRAMS (CONTINUED... Procedures § 89.406 Pre-test procedures. (a) Allow a minimum of 30 minutes warmup in the standby or operating...

  2. Optimization of C4.5 algorithm-based particle swarm optimization for breast cancer diagnosis

    Science.gov (United States)

    Muslim, M. A.; Rukmana, S. H.; Sugiharti, E.; Prasetiyo, B.; Alimah, S.

    2018-03-01

    Data mining has become a basic methodology for computational applications in the field of medical domains. Data mining can be applied in the health field such as for diagnosis of breast cancer, heart disease, diabetes and others. Breast cancer is most common in women, with more than one million cases and nearly 600,000 deaths occurring worldwide each year. The most effective way to reduce breast cancer deaths was by early diagnosis. This study aims to determine the level of breast cancer diagnosis. This research data uses Wisconsin Breast Cancer dataset (WBC) from UCI machine learning. The method used in this research is the algorithm C4.5 and Particle Swarm Optimization (PSO) as a feature option and to optimize the algorithm. C4.5. Ten-fold cross-validation is used as a validation method and a confusion matrix. The result of this research is C4.5 algorithm. The particle swarm optimization C4.5 algorithm has increased by 0.88%.

  3. Studies on the separation of {sup 89}Sr(II) from irradiated yttria target using 4, 4{sup '}(5{sup '}) di-tert-butyl-cyclohexano-18-crown-6 (DtBuCH18C6) by solvent extraction technique

    Energy Technology Data Exchange (ETDEWEB)

    Saha, Debasish; Vithya, Jayagopal; Kumar, Ramalingam; Venkata Subramani, Canchipuram Ramamoorthy; Vasudeva Rao, Polur Ranga [Indira Gandhi Centre for Atomic Research (IGCAR), Kalpakkam (India). Chemistry Group

    2016-07-01

    The radioisotope {sup 89}Sr as {sup 89}SrCl{sub 2} is medically useful for bone pain palliation and is produced in fast reactors using the {sup 89}Y(n, p){sup 89}Sr reaction. A procedure for isolation of the radionuclide {sup 89}Sr by chemical processing of the irradiated Y{sub 2}O{sub 3} target has been standardised and trial runs have been carried out at the Fast Breeder Test Reactor (FBTR), Kalpakkam. The chemical processing of the irradiated Y{sub 2}O{sub 3} target involves (i) the removal of target Y(III) by TBP extraction and (ii) further purification of the separated {sup 89}Sr fraction by cationic exchange chromatography. However a selective isolation of {sup 89}Sr by the Sr-specific crown ether makes the above chemical processing faster and relatively simple. This work presents a study on the selective removal of Sr from the irradiated target dissolver solution using the Sr-specific crown ether 4,4{sup '}(5{sup '}) di-tert-butyl-cyclohexano-18-crown-6 (DtBuCH18C6) in octanol medium. The separation behaviour of the other impurities such as Ce(IV), Y(III), Tb(III), Eu(III), Zn(II), Mn(II) and Rb(I) present along with Sr(II) in the irradiated sample was also investigated. The method of separation by using the crown ether DtBuCH18C6 is proved to be a potential tool for the purification of {sup 89}Sr(II) source produced from yttria target in fast reactors.

  4. 1 CFR 8.9 - Form of citation.

    Science.gov (United States)

    2010-01-01

    ... 1 General Provisions 1 2010-01-01 2010-01-01 false Form of citation. 8.9 Section 8.9 General Provisions ADMINISTRATIVE COMMITTEE OF THE FEDERAL REGISTER SPECIAL EDITIONS OF THE FEDERAL REGISTER CODE OF FEDERAL REGULATIONS § 8.9 Form of citation. The Code of Federal Regulations may be cited by title and...

  5. Pairwise comparison of {sup 89}Zr- and {sup 124}I-labeled cG250 based on positron emission tomography imaging and nonlinear immunokinetic modeling: in vivo carbonic anhydrase IX receptor binding and internalization in mouse xenografts of clear-cell renal cell carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Cheal, Sarah M.; Punzalan, Blesida; Doran, Michael G.; Osborne, Joseph R. [Memorial Sloan-Kettering Cancer Center, Department of Radiology, New York, NY (United States); Evans, Michael J. [Memorial Sloan-Kettering Cancer Center, Human Oncology and Pathogenesis Program, New York, NY (United States); Lewis, Jason S. [Memorial Sloan-Kettering Cancer Center, Department of Radiology, New York, NY (United States); Memorial Sloan-Kettering Cancer Center, Program in Molecular Pharmacology and Chemistry, New York, NY (United States); Memorial Sloan-Kettering Cancer Center, Radiochemistry and Imaging Sciences Service, New York, NY (United States); Zanzonico, Pat [Memorial Sloan-Kettering Cancer Center, Department of Radiology, New York, NY (United States); Memorial Sloan-Kettering Cancer Center, Molecular Pharmacology and Therapy Service, New York, NY (United States); Memorial-Sloan Kettering Cancer Center, New York, NY (United States); Larson, Steven M. [Memorial Sloan-Kettering Cancer Center, Department of Radiology, New York, NY (United States); Memorial Sloan-Kettering Cancer Center, Program in Molecular Pharmacology and Chemistry, New York, NY (United States); Memorial Sloan-Kettering Cancer Center, Molecular Pharmacology and Therapy Service, New York, NY (United States)

    2014-05-15

    The PET tracer, {sup 124}I-cG250, directed against carbonic anhydrase IX (CAIX) shows promise for presurgical diagnosis of clear-cell renal cell carcinoma (ccRCC) (Divgi et al. in Lancet Oncol 8:304-310, 2007; Divgi et al. in J Clin Oncol 31:187-194, 2013). The radiometal {sup 89}Zr, however, may offer advantages as a surrogate PET nuclide over {sup 124}I in terms of greater tumor uptake and retention (Rice et al. in Semin Nucl Med 41:265-282, 2011). We have developed a nonlinear immunokinetic model to facilitate a quantitative comparison of absolute uptake and antibody turnover between {sup 124}I-cG250 and {sup 89}Zr-cG250 using a human ccRCC xenograft tumor model in mice. We believe that this unique model better relates quantitative imaging data to the salient biological features of tumor antibody-antigen binding and turnover. We conducted experiments with {sup 89}Zr-cG250 and {sup 124}I-cG250 using a human ccRCC cell line (SK-RC-38) to characterize the binding affinity and internalization kinetics of the two tracers in vitro. Serial PET imaging was performed in mice bearing subcutaneous ccRCC tumors to simultaneously detect and quantify time-dependent tumor uptake in vivo. Using the known specific activities of the two tracers, the equilibrium rates of antibody internalization and turnover in the tumors were derived from the PET images using nonlinear compartmental modeling. The two tracers demonstrated virtually identical tumor cell binding and internalization but showed markedly different retentions in vitro. Superior PET images were obtained using {sup 89}Zr-cG250, owing to the more prolonged trapping of the radiolabel in the tumor and simultaneous washout from normal tissues. Estimates of cG250/CAIX complex turnover were 1.35 - 5.51 x 10{sup 12} molecules per hour per gram of tumor (20 % of receptors internalized per hour), and the ratio of {sup 124}I/{sup 89}Zr atoms released per unit time by tumor was 17.5. Pairwise evaluation of {sup 89}Zr-cG250 and {sup

  6. Genetic modifiers of CHEK2*1100delC-associated breast cancer risk

    DEFF Research Database (Denmark)

    Muranen, Taru A; Greco, Dario; Blomqvist, Carl

    2017-01-01

    PURPOSE: CHEK2*1100delC is a founder variant in European populations that confers a two- to threefold increased risk of breast cancer (BC). Epidemiologic and family studies have suggested that the risk associated with CHEK2*1100delC is modified by other genetic factors in a multiplicative fashion....... We have investigated this empirically using data from the Breast Cancer Association Consortium (BCAC). METHODS: Using genotype data from 39,139 (624 1100delC carriers) BC patients and 40,063 (224) healthy controls from 32 BCAC studies, we analyzed the combined risk effects of CHEK2*1100delC and 77...

  7. Clinical study of 89Sr therapy with radiosensitization by nicotinamide and carbogen in multiple bone metastasis of malignant neoplasms

    International Nuclear Information System (INIS)

    Liu Yajie; Wang Shubin; Guo Yiling; Chen Zuowei; Zhang Yingnan

    2005-01-01

    Objective: To evaluate the curative effect and side effects of 89 Sr therapy with radiosensitization by nicotinamide and carbogen in multiple bone metastasis of malignant neoplasms. Methods: Ninety-seven patients were divided into 4 groups respectively: group A, 89 Sr + nicotinamide + carbogen (24 patients); group B, 89 Sr + nicotinamide(22 patients); group C, 89 Sr + carbogen (25 patients); group D, 89 Sr, (26 patients). 89 SrCl was intravenously injected at a dose of 1.48-2.22 MBq/kg. Nicotinamide was taken orally 1 hour before 89 SrCl injection, 6 g/day, tid, d1-d5. Aspiration of carbogen(95%O 2 + 5%CO 2 ) gases, 6 L/min, 10 minutes, qd, d1-d5. Results: The effective rate of pain control and QOL improvement in A group were higher than in groups B, C and D (91.7% VS 77.3%, 76.0% and 69.2%, P=0.048). The lesions assessed by SPECT imaging in every group was not significantly different at three months after treatment. I to II degree toxic effect on bone marrow appeared in every group and there were no significantly inter-group differences. Conclusions: Combinative therapy using 89 Sr + nicotinamide + carbogen is more effective to treat multiple metastatic bone pain and for improvement of QOL. The side effects are not increased. (authors)

  8. 25 CFR 89.31 - Negotiation of contract.

    Science.gov (United States)

    2010-04-01

    ... 25 Indians 1 2010-04-01 2010-04-01 false Negotiation of contract. 89.31 Section 89.31 Indians BUREAU OF INDIAN AFFAIRS, DEPARTMENT OF THE INTERIOR TRIBAL GOVERNMENT ATTORNEY CONTRACTS WITH INDIAN TRIBES Five Civilized Tribes § 89.31 Negotiation of contract. That person or governing entity recognized as having authority to act for and in behalf o...

  9. 40 CFR 89.410 - Engine test cycle.

    Science.gov (United States)

    2010-07-01

    ... 40 Protection of Environment 20 2010-07-01 2010-07-01 false Engine test cycle. 89.410 Section 89... Procedures § 89.410 Engine test cycle. (a) Emissions shall be measured using one of the test cycles specified...) through (a)(4) of this section. These cycles shall be used to test engines on a dynamometer. (1) The 8...

  10. Macrocyclic peptides decrease c-Myc protein levels and reduce prostate cancer cell growth.

    Science.gov (United States)

    Mukhopadhyay, Archana; Hanold, Laura E; Thayele Purayil, Hamsa; Gisemba, Solomon A; Senadheera, Sanjeewa N; Aldrich, Jane V

    2017-08-03

    The oncoprotein c-Myc is often overexpressed in cancer cells, and the stability of this protein has major significance in deciding the fate of a cell. Thus, targeting c-Myc levels is an attractive approach for developing therapeutic agents for cancer treatment. In this study, we report the anti-cancer activity of the macrocyclic peptides [D-Trp]CJ-15,208 (cyclo[Phe-D-Pro-Phe-D-Trp]) and the natural product CJ-15,208 (cyclo[Phe-D-Pro-Phe-Trp]). [D-Trp]CJ-15,208 reduced c-Myc protein levels in prostate cancer cells and decreased cell proliferation with IC 50 values ranging from 2.0 to 16 µM in multiple PC cell lines. [D-Trp]CJ-15,208 induced early and late apoptosis in PC-3 cells following 48 hours treatment, and growth arrest in the G2 cell cycle phase following both 24 and 48 hours treatment. Down regulation of c-Myc in PC-3 cells resulted in loss of sensitivity to [D-Trp]CJ-15,208 treatment, while overexpression of c-Myc in HEK-293 cells imparted sensitivity of these cells to [D-Trp]CJ-15,208 treatment. This macrocyclic tetrapeptide also regulated PP2A by reducing the levels of its phosphorylated form which regulates the stability of cellular c-Myc protein. Thus [D-Trp]CJ-15,208 represents a new lead compound for the potential development of an effective treatment of prostate cancer.

  11. Age- and Tumor Subtype-Specific Breast Cancer Risk Estimates for CHEK2*1100delC Carriers

    DEFF Research Database (Denmark)

    Schmidt, Marjanka K; Hogervorst, Frans; van Hien, Richard R

    2016-01-01

    PURPOSE: CHEK2*1100delC is a well-established breast cancer risk variant that is most prevalent in European populations; however, there are limited data on risk of breast cancer by age and tumor subtype, which limits its usefulness in breast cancer risk prediction. We aimed to generate tumor...... subtype- and age-specific risk estimates by using data from the Breast Cancer Association Consortium, including 44,777 patients with breast cancer and 42,997 controls from 33 studies genotyped for CHEK2*1100delC. PATIENTS AND METHODS: CHEK2*1100delC genotyping was mostly done by a custom Taqman assay....... Breast cancer odds ratios (ORs) for CHEK2*1100delC carriers versus noncarriers were estimated by using logistic regression and adjusted for study (categorical) and age. Main analyses included patients with invasive breast cancer from population- and hospital-based studies. RESULTS: Proportions...

  12. Targeting c-Met in Cancer by MicroRNAs: Potential Therapeutic Applications in Hepatocellular Carcinoma.

    Science.gov (United States)

    Karagonlar, Zeynep F; Korhan, Peyda; Atabey, Neşe

    2015-11-01

    Preclinical Research Cancer is one of the world's deadliest diseases, with very low survival rates and increased occurrence in the future. Successfully developed target-based therapies have significantly changed cancer treatment. However, primary and/or acquired resistance in the tumor is a major challenge in current therapies and novel combinational therapies are required. RNA interference-mediated gene inactivation, alone or in combination with other current therapies, provides novel promising therapeutics that can improve cure rate and overcome resistance mechanisms to conventional therapeutics. Hepatocyte Growth Factor/c-Met signaling is one of the most frequently dysregulated pathways in human cancers and abnormal c-Met activation is correlated with poor clinical outcomes and drug resistance in hepatocellular carcinoma (HCC). In recent years, a growing number of studies have identified several inhibitors and microRNAs (miRNAs), specifically targeting c-Met in various cancers, including HCC. In this review, we discuss current knowledge regarding miRNAs, focusing on their involvement in cancer and their potential as research tools and therapeutics. Then, we focus on the potential use of c-Met targeting miRNAs for suppressing aberrant c-Met signaling in HCC treatment. © 2015 Wiley Periodicals, Inc.

  13. Unix version of CALOR89 for calorimeter applications

    International Nuclear Information System (INIS)

    Handler, T.

    1992-01-01

    CALOR89 is a system of coupled Monte Carlo particle transport computer codes which has been successfully employed for the estimation of calorimeter parameters in High Energy Physics. In the past CALOR89 has been running on various IBM machines and on CRAY X-MP at Lawrence Livermore Lab. These machines had non-unix operating systems. In this report we present a UNIX version of CALOR89, which is especially suited for the UNIX work stations. Moreover CALOR89 is also been supplemented with two new program packages which makes it more user friendly. CALPREP is a program for the preparation of the input files for CALOR89 in general geometry and ANALYZ is an analysis package to extract the final results from CALOR89 relevant to calorimeters. This report also provides two script files LCALOR and PCALOR. LCALOR runs CALOR89 sequences of programs and EGS4 for a given configuration sequentially on a single processor and PCALOR concurrently on a multiprocessor unix workstation

  14. Critical role of c-Jun overexpression in liver metastasis of human breast cancer xenograft model

    International Nuclear Information System (INIS)

    Zhang, Yan; Hu, Meiru; Shen, Beifen; Guo, Ning; Pu, Xiaoyun; Shi, Ming; Chen, Liyong; Song, Yuhua; Qian, Lu; Yuan, Guogang; Zhang, Hao; Yu, Ming

    2007-01-01

    c-Jun/AP-1 has been linked to invasive properties of aggressive breast cancer. Recently, it has been reported that overexpression of c-Jun in breast cancer cell line MCF-7 resulted in increased AP-1 activity, motility and invasiveness of the cells in vitro and tumor formation in nude mice. However, the role of c-Jun in metastasis of human breast cancer in vivo is currently unknown. To further investigate the direct involvement of c-Jun in tumorigenesis and metastasis, in the present study, the effects of c-Jun overexpression were studied in both in vitro and in nude mice. Ectopic overexpression of c-Jun promoted the growth of MCF-7 cells and resulted in a significant increase in the percentage of cells in S phase and increased motility and invasiveness. Introduction of c-Jun gene alone into weakly invasive MCF-7 cells resulted in the transfected cells capable of metastasizing to the nude mouse liver following tail vein injection. The present study confirms that overexpression of c-Jun contributes to a more invasive phenotype in MCF-7 cells. It indicates an interesting relationship between c-Jun expression and increased property of adhesion, migration and in vivo liver metastasis of MCF-7/c-Jun cells. The results provide further evidence that c-Jun is involved in the metastasis of breast cancer. The finding also opens an opportunity for development of anti-c-Jun strategies in breast cancer therapy

  15. MAGE-C2/CT10 protein expression is an independent predictor of recurrence in prostate cancer.

    Directory of Open Access Journals (Sweden)

    Lotta von Boehmer

    Full Text Available The cancer-testis (CT family of antigens is expressed in a variety of malignant neoplasms. In most cases, no CT antigen is found in normal tissues, except in testis, making them ideal targets for cancer immunotherapy. A comprehensive analysis of CT antigen expression has not yet been reported in prostate cancer. MAGE-C2/CT-10 is a novel CT antigen. The objective of this study was to analyze extent and prognostic significance of MAGE-C2/CT10 protein expression in prostate cancer. 348 prostate carcinomas from consecutive radical prostatectomies, 29 castration-refractory prostate cancer, 46 metastases, and 45 benign hyperplasias were immunohistochemically analyzed for MAGE-C2/CT10 expression using tissue microarrays. Nuclear MAGE-C2/CT10 expression was identified in only 3.3% primary prostate carcinomas. MAGE-C2/CT10 protein expression was significantly more frequent in metastatic (16.3% positivity and castration-resistant prostate cancer (17% positivity; p<0.001. Nuclear MAGE-C2/CT10 expression was identified as predictor of biochemical recurrence after radical prostatectomy (p = 0.015, which was independent of preoperative PSA, Gleason score, tumor stage, and surgical margin status in multivariate analysis (p<0.05. MAGE-C2/CT10 expression in prostate cancer correlates with the degree of malignancy and indicates a higher risk for biochemical recurrence after radical prostatectomy. Further, the results suggest MAGE-C2/CT10 as a potential target for adjuvant and palliative immunotherapy in patients with prostate cancer.

  16. 9 CFR 89.5 - Feeding pens.

    Science.gov (United States)

    2010-01-01

    ... 9 Animals and Animal Products 1 2010-01-01 2010-01-01 false Feeding pens. 89.5 Section 89.5 Animals and Animal Products ANIMAL AND PLANT HEALTH INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE INTERSTATE TRANSPORTATION OF ANIMALS (INCLUDING POULTRY) AND ANIMAL PRODUCTS STATEMENT OF POLICY UNDER THE...

  17. Oncoplastic breast surgery does not delay the onset of adjuvant chemotherapy

    DEFF Research Database (Denmark)

    Klit, Anders; Tvedskov, Tove Filtenborg; Kroman, Niels

    2017-01-01

    BACKGROUND: Only a few studies of limited size have examined whether oncoplastic breast surgery delays the onset of adjuvant chemotherapy as compared to conventional breast surgery. We investigated whether oncoplastic breast surgery causes a delay in the onset of adjuvant chemotherapy in comparison...... to lumpectomy and mastectomy. MATERIAL AND METHODS: The study is a population-based cohort study. Within the nationwide registry of the Danish Breast Cancer Group (DBCG), we identified 1798 patients who received adjuvant chemotherapy following mastectomy, lumpectomy or oncoplastic breast surgery for early...... and unilateral invasive breast cancer. Women treated with neoadjuvant chemotherapy were excluded. RESULTS: We found no significant difference between the three groups (mastectomy, lumpectomy, oncoplastic breast surgery) in the time from biopsy to surgery (mean time 17.9, 17.0 and 18.3 days, respectively...

  18. CDKN1C/p57kip2 is a candidate tumor suppressor gene in human breast cancer

    International Nuclear Information System (INIS)

    Larson, Pamela S; Schlechter, Benjamin L; King, Chia-Lin; Yang, Qiong; Glass, Chelsea N; Mack, Charline; Pistey, Robert; Morenas, Antonio de las; Rosenberg, Carol L

    2008-01-01

    CDKN1C (also known as p57 KIP2 ) is a cyclin-dependent kinase inhibitor previously implicated in several types of human cancer. Its family members (CDKN1A/p21 CIP1 and B/p27 KIP1 ) have been implicated in breast cancer, but information about CDKN1C's role is limited. We hypothesized that decreased CDKN1C may be involved in human breast carcinogenesis in vivo. We determined rates of allele imbalance or loss of heterozygosity (AI/LOH) in CDKN1C, using an intronic polymorphism, and in the surrounding 11p15.5 region in 82 breast cancers. We examined the CDKN1C mRNA level in 10 cancers using quantitative real-time PCR (qPCR), and the CDKN1C protein level in 20 cancers using immunohistochemistry (IHC). All samples were obtained using laser microdissection. Data were analyzed using standard statistical tests. AI/LOH at 11p15.5 occurred in 28/73 (38%) informative cancers, but CDKN1C itself underwent AI/LOH in only 3/16 (19%) cancers (p = ns). In contrast, CDKN1C mRNA levels were reduced in 9/10 (90%) cancers (p < 0.0001), ranging from 2–60% of paired normal epithelium. Similarly, CDKN1C protein staining was seen in 19/20 (95%) cases' normal epithelium but in only 7/14 (50%) cases' CIS (p < 0.004) and 5/18 (28%) cases' IC (p < 0.00003). The reduction appears primarily due to loss of CDKN1C expression from myoepithelial layer cells, which stained intensely in 17/20 (85%) normal lobules, but in 0/14 (0%) CIS (p < 0.00001). In contrast, luminal cells displayed less intense, focal staining fairly consistently across histologies. Decreased CDKN1C was not clearly associated with tumor grade, histology, ER, PR or HER2 status. CDKN1C is expressed in normal epithelium of most breast cancer cases, mainly in the myothepithelial layer. This expression decreases, at both the mRNA and protein level, in the large majority of breast cancers, and does not appear to be mediated by AI/LOH at the gene. Thus, CDKN1C may be a breast cancer tumor suppressor

  19. Metabolic Effects of Hypoxia in Colorectal Cancer by 13C NMR Isotopomer Analysis

    Directory of Open Access Journals (Sweden)

    Ana M. Abrantes

    2014-01-01

    Full Text Available 13C NMR isotopomer analysis was used to characterize intermediary metabolism in three colorectal cancer cell lines (WiDr, LS1034, and C2BBe1 and determine the “metabolic remodeling” that occurs under hypoxia. Under normoxia, the three colorectal cancer cell lines present high rates of lactate production and can be seen as “Warburg” like cancer cells independently of substrate availability, since such profile was dominant at both high and low glucose media contents. The LS1034 was the less glycolytic of the three cell lines and was the most affected by the event of hypoxia, raising abruptly glucose consumption and lactate production. The other two colorectal cell lines, WiDr and C2BBe1, adapted better to hypoxia and were able to maintain their oxidative fluxes even at the very low levels of oxygen. These differential metabolic behaviors of the three colorectal cell lines show how important an adequate knowledge of the “metabolic remodeling” that follows a given cancer treatment is towards the correct (redesign of therapeutic strategies against cancer.

  20. Genetic and genomic analysis modeling of germline c-MYC overexpression and cancer susceptibility

    Directory of Open Access Journals (Sweden)

    Nunes Virginia

    2008-01-01

    Full Text Available Abstract Background Germline genetic variation is associated with the differential expression of many human genes. The phenotypic effects of this type of variation may be important when considering susceptibility to common genetic diseases. Three regions at 8q24 have recently been identified to independently confer risk of prostate cancer. Variation at 8q24 has also recently been associated with risk of breast and colorectal cancer. However, none of the risk variants map at or relatively close to known genes, with c-MYC mapping a few hundred kilobases distally. Results This study identifies cis-regulators of germline c-MYC expression in immortalized lymphocytes of HapMap individuals. Quantitative analysis of c-MYC expression in normal prostate tissues suggests an association between overexpression and variants in Region 1 of prostate cancer risk. Somatic c-MYC overexpression correlates with prostate cancer progression and more aggressive tumor forms, which was also a pathological variable associated with Region 1. Expression profiling analysis and modeling of transcriptional regulatory networks predicts a functional association between MYC and the prostate tumor suppressor KLF6. Analysis of MYC/Myc-driven cell transformation and tumorigenesis substantiates a model in which MYC overexpression promotes transformation by down-regulating KLF6. In this model, a feedback loop through E-cadherin down-regulation causes further transactivation of c-MYC. Conclusion This study proposes that variation at putative 8q24 cis-regulator(s of transcription can significantly alter germline c-MYC expression levels and, thus, contribute to prostate cancer susceptibility by down-regulating the prostate tumor suppressor KLF6 gene.

  1. [{sup 11}C]Choline PET/CT detection of bone metastases in patients with PSA progression after primary treatment for prostate cancer: comparison with bone scintigraphy

    Energy Technology Data Exchange (ETDEWEB)

    Picchio, Maria [San Raffaele Scientific Institute, Nuclear Medicine Department, Milan (Italy); National Research Council (IBFM-CNR), Institute for Bioimaging and Molecular Physiology, Milan (Italy); Spinapolice, Elena Giulia; Crivellaro, Cinzia [University of Milano-Bicocca, Center for Molecular Bioimaging, Milan (Italy); Fallanca, Federico; Gianolli, Luigi [San Raffaele Scientific Institute, Nuclear Medicine Department, Milan (Italy); Giovacchini, Giampiero [University of Milano-Bicocca, Center for Molecular Bioimaging, Milan (Italy); University Hospital Basel, Institute of Nuclear Medicine, Basel (Switzerland); Messa, Cristina [National Research Council (IBFM-CNR), Institute for Bioimaging and Molecular Physiology, Milan (Italy); University of Milano-Bicocca, Center for Molecular Bioimaging, Milan (Italy); San Gerardo Hospital, Department of Nuclear Medicine, Monza (Italy)

    2012-01-15

    The aim of this study was to evaluate the clinical usefulness of [{sup 11}C]choline positron emission tomography (PET)/CT in comparison with bone scintigraphy (BS) in detecting bone metastases (BM) of patients with biochemical progression after radical treatment for prostate cancer (PCa). Seventy-eight consecutive patients with biochemical progression of PCa (mean prostate-specific antigen 21.1 ng/ml, range 0.2-500.0 ng/ml) referred for both [{sup 11}C]choline PET/CT and BS for restaging purposes were retrospectively analysed. The diagnostic accuracy of [{sup 11}C]choline PET/CT and BS was assessed by using morphological imaging and/or follow-up as standards of reference. As equivocal findings were found, the accuracy analysis was performed twice, once including them as positive and once as negative. A separate analysis was also performed in hormone-resistant patients and data compared with those of patients who did not receive anti-androgenic treatment. Equivocal findings occurred in 1 of 78 (1%) cases in [{sup 11}C]choline PET/CT and in 21 of 78 (27%) cases in BS. Depending on their attribution as either positive or negative, the ranges of sensitivity, specificity, positive predictive value, negative predictive value and accuracy for [{sup 11}C]choline PET/CT were 89-89%, 98-100%, 96-100%, 94-96% and 95-96%, respectively. For BS they were 100-70%, 75-100%, 68-100%, 100-86% and 83-90%, respectively. Concordant findings between [{sup 11}C]choline PET/CT and BS occurred in 55 of 78 (71%) cases. The accuracy of [{sup 11}C]choline PET/CT did not significantly (p = 0.30) differ between hormone-resistant patients (97%) and those who did not receive anti-androgenic treatment (95%). In clinical practice, [{sup 11}C]choline PET/CT may not replace BS because of its lower sensitivity. However, for its high specificity, [{sup 11}C]choline PET/CT positive findings may accurately predict the presence of BM. Equivocal findings are more frequent in BS than [{sup 11}C]choline PET

  2. 40 CFR 745.89 - Firm certification.

    Science.gov (United States)

    2010-07-01

    ... 40 Protection of Environment 30 2010-07-01 2010-07-01 false Firm certification. 745.89 Section 745... § 745.89 Firm certification. (a) Initial certification. (1) Firms that perform renovations for compensation must apply to EPA for certification to perform renovations or dust sampling. To apply, a firm must...

  3. 40 CFR 141.89 - Analytical methods.

    Science.gov (United States)

    2010-07-01

    ... 40 Protection of Environment 22 2010-07-01 2010-07-01 false Analytical methods. 141.89 Section 141...) NATIONAL PRIMARY DRINKING WATER REGULATIONS Control of Lead and Copper § 141.89 Analytical methods. (a... shall be conducted with the methods in § 141.23(k)(1). (1) Analyses for alkalinity, calcium...

  4. Targeting chemokine (C-C motif) ligand 2 (CCL2) as an example of translation of cancer molecular biology to the clinic.

    Science.gov (United States)

    Zhang, Jian; Patel, Lalit; Pienta, Kenneth J

    2010-01-01

    Chemokines are a family of small and secreted proteins that play pleiotropic roles in inflammation-related pathological diseases, including cancer. Among the identified 50 human chemokines, chemokine (C-C motif) ligand 2 (CCL2) is of particular importance in cancer development since it serves as one of the key mediators of interactions between tumor and host cells. CCL2 is produced by cancer cells and multiple different host cells within the tumor microenvironment. CCL2 mediates tumorigenesis in many different cancer types. For example, CCL2 has been reported to promote prostate cancer cell proliferation, migration, invasion, and survival, via binding to its functional receptor CCR2. Furthermore, CCL2 induces the recruitment of macrophages and induces angiogenesis and matrix remodeling. Targeting CCL2 has been demonstrated as an effective therapeutic approach in preclinical prostate cancer models, and currently, neutralizing monoclonal antibody against CCL2 has entered into clinical trials in prostate cancer. In this chapter, targeting CCL2 in prostate cancer will be used as an example to show translation of laboratory findings from cancer molecular biology to the clinic. Copyright © 2010 Elsevier Inc. All rights reserved.

  5. c.29C>T polymorphism in the transforming growth factor-β1 (TGFB1) gene correlates with increased risk of urinary bladder cancer.

    Science.gov (United States)

    Gautam, Kirti Amresh; Pooja, Singh; Sankhwar, Satya Narayan; Sankhwar, Pushp Lata; Goel, Apul; Rajender, Singh

    2015-10-01

    TGF-β1 is a pleiotropic cytokine, which plays a dual role in tumor development. In the early stages, it inhibits the growth of tumor while in the late stages of carcinoma, it promotes tumor growth. The purpose of this study was to analyze the distribution of the TGFB1 gene polymorphisms between cases and controls so as to assess their correlation with bladder cancer risk. This study included 237 cases of urinary bladder cancer and 290 age matched controls from the same ethnic background. Three polymorphisms in the TGFB1 gene, c.29C>T (rs-1800470), c.74G>C (rs-1800471) and +140A>G (rs-13447341), were analyzed by direct DNA sequencing. Statistical analyses revealed no significant differences in the demographical data, except that the frequencies of smokers and non-vegetarians were higher in the cases. Eighty percent of the bladder cancer patients had superficial transitional cell carcinoma, and 53.16% and 26.31% of the patients were in grade I and grade II, respectively. We found that c.29C>T substitution increased the risk of bladder cancer significantly and recessive model of analysis was the best fitted model (p=0.004; OR=1.72 95% CI 1.18-2.50). A significantly higher risk in the recessive form was also suggested by co-dominant analysis showing that the homozygous form (TT) was a significant risk factor in comparison to CC and CT genotypes. The other two polymorphisms, c.74G>C (p=0.18, OR=0.67 95% CI 0.37-1.21) and +140A>G (p=0.416, OR=0.77 95% CI 0.41-1.45) did not affect the risk of urinary bladder cancer. In conclusion, we found that the TGFB1 c.29C>T substitution increases the risk of bladder cancer significantly while c.74G>C and +140A>G polymorphisms do not affect the risk. Copyright © 2015 Elsevier Ltd. All rights reserved.

  6. Vascular endothelial growth factor C promotes cervical cancer cell invasiveness via regulation of microRNA-326/cortactin expression.

    Science.gov (United States)

    Cheng, Yang; Jiang, Shuyi; Yuan, Jin; Liu, Junxiu; Simoncini, Tommaso

    2018-04-16

    Vascular endothelial growth factor C (VEGF-C) accelerates cervical cancer metastasis, while the detailed mechanism remains largely unknown. Recent evidence indicates that microRNA play a crucial role in controlling cancer cell invasiveness. In the present study, we investigated the role of miR-326 in VEGF-C-induced cervical cancer cell invasion. VEGF-C expression was higher and miR-326 was much lower in primary cervical cancer specimens than that in non-cancerous specimens, and a negative correlation between VEGF-C and miR-326 was found. On cervical carcinoma cell line SiHa cells, treatment with VEGF-C downregulated miR-326 level and increased cortactin protein expression. Transfection with miR-326 mimic reversed cortactin expression induced by VEGF-C, suggesting that VEGF-C increased cortactin via downregulation of miR-326. VEGF-C activated c-Src and c-Src inhibitor PP2 abolished VEGF-C effect on miR-326 and cortactin expression, implying that VEGF-C regulated miR-326/cortactin via c-Src signaling. VEGF-C promoted SiHa cell invasion index, which was largely inhibited by transfection with miR-326 antagonist or by siRNA against cortactin. In conclusion, our findings implied that VEGF-C reduced miR-326 expression and increased cortactin expression through c-Src signaling, leading to enhanced cervical cancer invasiveness. This may shed light on potential therapeutic strategies for cervical cancer therapy.

  7. Prognostic significance of cancer within 1 mm of the circumferential resection margin in oesophageal cancer patients following neo-adjuvant chemotherapy.

    Science.gov (United States)

    Salih, Tamir; Jose, Paul; Mehta, Samir P; Mirza, Ahmed; Udall, Gavin; Pritchard, Susan A; Hayden, Jeremy D; Grabsch, Heike I

    2013-03-01

    The prognostic significance of the circumferential resection margin (CRM) status in oesophageal cancer patients treated with neo-adjuvant chemotherapy and radical resection is controversial. Furthermore, it is currently unclear whether patients with cancer located at the CRM have a prognosis different from that of those with cancer within 1 mm of the CRM. This is the first study aiming to establish the optimal tumour-free distance from the CRM of an oesophagectomy in patients who have undergone neo-adjuvant chemotherapy. The clinicopathological data of 232 oesophageal cancer patients from two UK centres were analysed. The CRM status was classified as Group A (cancer at the CRM), Group B (cancer within 1 mm but not at the CRM) and Group C (no cancer within 1 mm from the CRM). The relationship between the CRM status and patient survival was investigated. Thirty-eight specimens were classified as Group A, 89 as Group B and 105 as Group C. CRM status was related to the depth of tumour invasion (P CRM or within 1 mm of the CRM of the resected specimen have a significantly worse survival than patients with no cancer cells within 1 mm of the margin. However, this study suggests that the overall prognostic significance of the CRM status is limited in this cohort and the postoperative lymph node status is the most important prognostic factor in oesophageal cancer patients treated with neo-adjuvant chemotherapy and surgery.

  8. Utilising cardiopulmonary bypass for cancer surgery. Malignancy-induced protein C deficiency and thrombophilia.

    LENUS (Irish Health Repository)

    Marshall, C

    2012-02-03

    Cardiopulmonary bypass has evolved over the last 30 years. It is an important tool for the cardiac surgeon today and also has applications in non-cardiac operations such as surgery to extract tumours. Such patients undergoing surgery for cancer may be at an increased risk of a thromboembolic event post surgery, due to disturbances in the normal clotting pathway leading to hypercoagulability. One such disturbance is malignancy-induced Protein C deficiency. A deficiency of Protein C can cause hypercoagulabitity. Recent studies have examined cardiopulmonary bypass and inherited Protein C deficiency. However, surgery for cancer patients with a malignancy-induced Protein C deficiency involving cardiopulmonary bypass has not been reported. Surgery using CPB in these patients may result in increased morbidity and mortality. The objective of this article is to review the literature in order to discuss the occurrence, the aetiology and possible management of cancer patients with malignancy-induced Protein C deficiencies that require cardiopulmonary bypass for their surgery.

  9. A Modified Bacillus Calmette-Guérin (BCG Vaccine with Reduced Activity of Antioxidants and Glutamine Synthetase Exhibits Enhanced Protection of Mice despite Diminished in Vivo Persistence

    Directory of Open Access Journals (Sweden)

    Douglas S. Kernodle

    2013-01-01

    Full Text Available Early attempts to improve BCG have focused on increasing the expression of prominent antigens and adding recombinant toxins or cytokines to influence antigen presentation. One such modified BCG vaccine candidate has been withdrawn from human clinical trials due to adverse effects. BCG was derived from virulent Mycobacterium bovis and retains much of its capacity for suppressing host immune responses. Accordingly, we have used a different strategy for improving BCG based on reducing its immune suppressive capacity. We made four modifications to BCG Tice to produce 4dBCG and compared it to the parent vaccine in C57Bl/6 mice. The modifications included elimination of the oxidative stress sigma factor SigH, elimination of the SecA2 secretion channel, and reductions in the activity of iron co-factored superoxide dismutase and glutamine synthetase. After IV inoculation of 4dBCG, 95% of vaccine bacilli were eradicated from the spleens of mice within 60 days whereas the titer of BCG Tice was not significantly reduced. Subcutaneous vaccination with 4dBCG produced greater protection than vaccination with BCG against dissemination of an aerosolized challenge of M. tuberculosis to the spleen at 8 weeks post-challenge. At this time, 4dBCG-vaccinated mice also exhibited altered lung histopathology compared to BCG-vaccinated mice and control mice with less well-developed lymphohistiocytic nodules in the lung parenchyma. At 26 weeks post-challenge, 4dBCG-vaccinated mice but not BCG-vaccinated mice had significantly fewer challenge bacilli in the lungs than control mice. In conclusion, despite reduced persistence in mice a modified BCG vaccine with diminished antioxidants and glutamine synthetase is superior to the parent vaccine in conferring protection against M. tuberculosis. The targeting of multiple immune suppressive factors produced by BCG is a promising strategy for simultaneously improving vaccine safety and effectiveness.

  10. Evaluation of 89 compounds for identification of substrates for cynomolgus monkey CYP2C76, a new bupropion/nifedipine oxidase.

    Science.gov (United States)

    Hosaka, Shinya; Murayama, Norie; Satsukawa, Masahiro; Shimizu, Makiko; Uehara, Shotaro; Fujino, Hideki; Iwasaki, Kazuhide; Iwano, Shunsuke; Uno, Yasuhiro; Yamazaki, Hiroshi

    2015-01-01

    Cynomolgus monkeys are widely used in preclinical studies during drug development because of their evolutionary closeness to humans, including their cytochrome P450s (P450s). Most cynomolgus monkey P450s are almost identical (≥90%) to human P450s; however, CYP2C76 has low sequence identity (approximately 80%) to any human CYP2Cs. Although CYP2C76 has no ortholog in humans and is partly responsible for species differences in drug metabolism between cynomolgus monkeys and humans, a broad evaluation of potential substrates for CYP2C76 has not yet been conducted. In this study, a screening of 89 marketed compounds, including human CYP2C and non-CYP2C substrates or inhibitors, was conducted to find potential CYP2C76 substrates. Among the compounds screened, 19 chemicals were identified as substrates for CYP2C76, including substrates for human CYP1A2 (7-ethoxyresorufin), CYP2B6 (bupropion), CYP2D6 (dextromethorphan), and CYP3A4/5 (dextromethorphan and nifedipine), and inhibitors for CYP2B6 (sertraline, clopidogrel, and ticlopidine), CYP2C8 (quercetin), CYP2C19 (ticlopidine and nootkatone), and CYP3A4/5 (troleandomycin). CYP2C76 metabolized a wide variety of the compounds with diverse structures. Among them, bupropion and nifedipine showed high selectivity to CYP2C76. As for nifedipine, CYP2C76 formed methylhydroxylated nifedipine, which was not produced by monkey CYP2C9, CYP2C19, or CYP3A4, as identified by mass spectrometry and estimated by a molecular docking simulation. This unique oxidative metabolite formation of nifedipine could be one of the selective marker reactions of CYP2C76 among the major CYP2Cs and CYP3As tested. These results suggest that monkey CYP2C76 contributes to bupropion hydroxylation and formation of different nifedipine oxidative metabolites as a result of its relatively large substrate cavity. Copyright © 2014 by The American Society for Pharmacology and Experimental Therapeutics.

  11. Elevated pre-treatment levels of plasma C-reactive protein are associated with poor prognosis after breast cancer

    DEFF Research Database (Denmark)

    Allin, Kristine H; Nordestgaard, Børge G; Flyger, Henrik

    2011-01-01

    We examined whether plasma C-reactive protein (CRP) levels at the time of diagnosis of breast cancer are associated with overall survival, disease-free survival, death from breast cancer, and recurrence of breast cancer.......We examined whether plasma C-reactive protein (CRP) levels at the time of diagnosis of breast cancer are associated with overall survival, disease-free survival, death from breast cancer, and recurrence of breast cancer....

  12. El cáncer de pulmón como marcador de tabaquismo: relación con la mortalidad por cáncer no pulmonar Lung cancer as an index of tobacco exposure: association with non-lung cancer mortality

    Directory of Open Access Journals (Sweden)

    Mónica Pérez-Ríos

    2009-06-01

    Full Text Available Objetivo: Valorar el papel del tabaquismo, empleando como proxy la mortalidad por cáncer de pulmón, en la mortalidad por otros cánceres (excluyendo el de estómago. Métodos: Análisis de series temporales de mortalidad por cáncer en los hombres españoles (1970-2003 para valorar la posible asociación entre cáncer de pulmón y los cánceres «no pulmón-no estómago» (NPNE. Para evitar el efecto de posibles autocorrelaciones se aplicó la regresión Prais-Winsten. Resultados: Las tasas anuales de mortalidad por cánceres NPNE están linealmente relacionadas con la mortalidad por cáncer de pulmón en el período 1970-2003, con una pendiente de la recta de 1,07, intervalo de confianza del 95% de 0,98-1,17 y R² de 0,97. Conclusiones: Las variaciones de las tasas de mortalidad por cánceres NPNE pueden ser modeladas en función de los cambios en las tasas de mortalidad por cáncer de pulmón en el período estudiado. Los resultados presentados parecen mostrar una posible asociación entre el tabaquismo y los cánceres NPNE.Objective: To assess the possible role of tobacco smoke in non-lung cancer (excluding stomach cancer using changes in lung cancer mortality rates as a proxy for tobacco exposure. Methods: A time series analysis of cancer mortality was performed to evaluate the possible association between changes in mortality rates for lung cancer and for non-lung, non-stomach cancer (NLNS from 1970 to 2003 in Spanish males. To avoid problems with autocorrelation, Prais-Winsten regression was applied. Results: Changes in NLNS cancer death rates showed a parallel trend with lung cancer death rates in the study period, with an adjusted slope of 1.07, 95% CI of 0.98-1.17, and R² of 0.97. Conclusion: Variation in NLNS cancer death rates can be accurately modelled as a function of changes in lung cancer death rates for the study period, suggesting a possible association between tobacco exposure and NLNS cancers.

  13. CHEK2*1100delC Heterozygosity in Women With Breast Cancer Associated With Early Death, Breast Cancer-Specific Death, and Increased Risk of a Second Breast Cancer

    DEFF Research Database (Denmark)

    Weischer, Maren; Nordestgaard, Børge G; Pharoah, Paul

    2012-01-01

    PURPOSE We tested the hypotheses that CHEK2*1100delC heterozygosity is associated with increased risk of early death, breast cancer-specific death, and risk of a second breast cancer in women with a first breast cancer. PATIENTS AND METHODS From 22 studies participating in the Breast Cancer Assoc...

  14. Association between dietary vitamin C intake and risk of esophageal cancer: A dose-response meta-analysis.

    Science.gov (United States)

    Bo, Yacong; Lu, Yan; Zhao, Yan; Zhao, Erjiang; Yuan, Ling; Lu, Weiquan; Cui, Lingling; Lu, Quanjun

    2016-04-15

    While several epidemiological studies have investigated the association between vitamin C and risk of esophageal cancer, the results remain inconsistent. In the present study, a meta-analysis was conducted to assess the impact of dietary vitamin C intake on esophageal cancer risk. Online databases were searched up to March 29, 2015, for studies on the association between dietary vitamin C intake and esophageal cancer risk. Pooled risk ratios (RRs) or odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using a random-effects model. Dose-response analyses were performed using the method of restricted cubic splines with four knots at percentiles of 5, 35, 65 and 95% of the distribution. Publication bias was estimated using Egger's tests and funnel plots. In all, 15 articles were included in this meta-analysis, including 20 studies, containing 7063 controls and 3955 cases of esophageal cancer. By comparing the highest vs. the lowest categories of vitamin C intake, we found that vitamin C was inversely associated with the risk of esophageal cancer [overall OR = 0.58, 95% CI = 0.49-0.68, I(2) = 56%]. A linear dose-response relationship was found. With an increase in dietary vitamin C intake of 50 mg/day, the risk of esophageal cancer statistically decreased by 13% (OR = 0.87, 95% CI = 0.80-0.93, p(linearity) = 0.0002). In conclusion, our analysis suggested that the higher intake of dietary vitamin C might have a protective effect against esophageal cancer. © 2015 UICC.

  15. MMTV-Wnt1 and -DeltaN89beta-catenin induce canonical signaling in distinct progenitors and differentially activate Hedgehog signaling within mammary tumors.

    Directory of Open Access Journals (Sweden)

    Brigitte Teissedre

    Full Text Available Canonical Wnt/beta-catenin signaling regulates stem/progenitor cells and, when perturbed, induces many human cancers. A significant proportion of human breast cancer is associated with loss of secreted Wnt antagonists and mice expressing MMTV-Wnt1 and MMTV-DeltaN89beta-catenin develop mammary adenocarcinomas. Many studies have assumed these mouse models of breast cancer to be equivalent. Here we show that MMTV-Wnt1 and MMTV-DeltaN89beta-catenin transgenes induce tumors with different phenotypes. Using axin2/conductin reporter genes we show that MMTV-Wnt1 and MMTV-DeltaN89beta-catenin activate canonical Wnt signaling within distinct cell-types. DeltaN89beta-catenin activated signaling within a luminal subpopulation scattered along ducts that exhibited a K18(+ER(-PR(-CD24(highCD49f(low profile and progenitor properties. In contrast, MMTV-Wnt1 induced canonical signaling in K14(+ basal cells with CD24/CD49f profiles characteristic of two distinct stem/progenitor cell-types. MMTV-Wnt1 produced additional profound effects on multiple cell-types that correlated with focal activation of the Hedgehog pathway. We document that large melanocytic nevi are a hitherto unreported hallmark of early hyperplastic Wnt1 glands. These nevi formed along the primary mammary ducts and were associated with Hedgehog pathway activity within a subset of melanocytes and surrounding stroma. Hh pathway activity also occurred within tumor-associated stromal and K14(+/p63(+ subpopulations in a manner correlated with Wnt1 tumor onset. These data show MMTV-Wnt1 and MMTV-DeltaN89beta-catenin induce canonical signaling in distinct progenitors and that Hedgehog pathway activation is linked to melanocytic nevi and mammary tumor onset arising from excess Wnt1 ligand. They further suggest that Hedgehog pathway activation maybe a critical component and useful indicator of breast tumors arising from unopposed Wnt1 ligand.

  16. The diagnostic value of PSA, cPSA and bone scintigraphy for early skeletal metastasis of prostate cancer

    International Nuclear Information System (INIS)

    Xue Zhongguang

    2007-01-01

    Objective: To evaluate the value of prostate specific antigen (PSA), complexed prostate specific antigen (cPSA) and bone scintigraphic imaging in diagnosis of early skeletal metastasis of prostate cancer. Methods: 152 patients (74 with prostate cancer, 78 with benign prostate disease) and 90 controls were examined for the serum concentrations of PSA and cPSA. At the same time, the 74 patients with PCa were examined with bone scintigraphy. The cPSA/PSA ratio was calculated. Results: Serum PSA, cPSA levels and cPSA/PSA ratio of patients with prostate cancer were significantly higher than those in benign prostate patients and controls. In addition, the serum PSA, cPSA levels and cPSA/PSA ratio in prostate cancer patients with skeletal metastasis were remarkably higher than those in patients without skeletal metastasis, and the differences were significant (P 20 μg/L, cPSA>10 μg/L, cPSA/PSA>0.80, there is a high probability that skeletal metastasis of prostate cancer would be present and bone scintigraphy should be performed. (authors)

  17. cGMP signaling as a target for the prevention and treatment of breast cancer.

    Science.gov (United States)

    Windham, Perrin F; Tinsley, Heather N

    2015-04-01

    One in eight women in the United States will be diagnosed with invasive breast cancer in her lifetime. Advances in therapeutic strategies, diagnosis, and improved awareness have resulted in a significant reduction in breast cancer related mortality. However, there is a continued need for more effective and less toxic drugs for both the prevention and the treatment of breast cancer in order to see a continued decline in the morbidity and mortality associated with this disease. Recent studies suggest that the cGMP signaling pathway may be aberrantly regulated in breast cancer. As such, this pathway may serve as a source of novel targets for future breast cancer drug discovery efforts. This review provides an overview of cGMP signaling in normal physiology and in breast cancer as well as current strategies being investigated for targeting this pathway in breast cancer. Copyright © 2014 Elsevier Ltd. All rights reserved.

  18. 33 CFR 401.89 - Transit refused.

    Science.gov (United States)

    2010-07-01

    ... 33 Navigation and Navigable Waters 3 2010-07-01 2010-07-01 false Transit refused. 401.89 Section... TRANSPORTATION SEAWAY REGULATIONS AND RULES Regulations General § 401.89 Transit refused. (a) An officer may refuse to allow a vessel to transit when, (1) The vessel is not equipped in accordance with §§ 401.5 to...

  19. The catalase C-262T gene polymorphism and cancer risk: a systematic review and meta-analysis.

    Science.gov (United States)

    Shen, Yongchun; Li, Diandian; Tian, Panwen; Shen, Konglong; Zhu, Jing; Feng, Mei; Wan, Chun; Yang, Ting; Chen, Lei; Wen, Fuqiang

    2015-04-01

    Many studies suggest that catalase C-262T gene polymorphism is associated with cancer risk, but with inconsistent results. This study aimed to summarize the overall association between catalase C-262T polymorphism and cancer risk. Literature search was performed in PubMed, Embase, and other databases, studies regarding the association between catalase C-262T polymorphism and cancer risk were identified, and data were retrieved and analyzed by using Review Manager 5.0.24 and STATA 12.0. A total of 18 publications with 22 case-control studies, including 9777 cancer patients and 12,223 controls, met the inclusion criteria. Meta-analysis results showed significant association between catalase C-262 T polymorphism and cancer risk (TT vs CT + CC: odds ratio [OR] = 1.17, 95% confidence interval [CI] = 1.03-1.31, P = 0.01). Subgroup analyses stratified by cancer types suggested the catalase C-262T polymorphism was significantly associated with an increased prostate cancer risk (TT vs CT + CC: OR = 1.61, 95% CI = 1.17-2.22, P = 0.004); for subgroup analyses stratified by ethnicity, no associations between this polymorphism and Asians or whites were identified (CT + TT vs CC: OR = 1.11, 95% CI = 0.98-1.26, P = 0.09 for whites; OR = 1.19, 95% CI = 0.78-1.80, P = 0.42 for Asians). In summary, the catalase C-262T polymorphism may be a risk factor for cancer with cancer type-specific effects. Further studies should be performed to confirm these findings.

  20. Elevated C-reactive protein in the diagnosis, prognosis, and cause of cancer

    DEFF Research Database (Denmark)

    Allin, Kristine H; Nordestgaard, Børge G

    2011-01-01

    The aim of this review is to summarize present evidence of an association between circulating levels of C-reactive protein (CRP) and cancer risk, and to evaluate whether elevated circulating CRP levels cause cancer. Additionally, the review provides background information on the acute......-phase response, chronic inflammation, the molecular biology, function and measurement of CRP, circulating levels of CRP in health and disease, the principle of Mendelian randomization, the association between circulating levels of CRP and cancer prognosis, and cancer biomarkers. In the Copenhagen General...... increased risk of death from breast cancer compared to patients with CRP levels...

  1. 11C-harmine as a potential PET tracer for ductal pancreas cancer: in vitro studies

    International Nuclear Information System (INIS)

    Herlin, G.; Persson, B.; Laangstroem, B.; Aspelin, P.; Bergstroem, M.

    2003-01-01

    Our objective was to find a tracer in diagnosing human pancreatic cancer using positron emission tomography (PET). For this purpose in vitro test of pancreatic tissues with autoradiography was used. Autoradiography was performed with 11 C-harmine (a MAO-A-inhibitor) with and without competitive inhibition. Tissue preparations were obtained from normal human pancreas and pancreatic cancer. The uptake was compared with rat brain or pig brain, tissues with high expression of MAO-A. Nine autoradiography studies on 16 samples from five different human pancreatic cancers gave a significant level of specific binding of 11 C-harmine in 13, and 3 samples did not give a significant level of specific binding of 11 C-harmine. All 16 samples were analysed with autoradiography. Compared with rat brain, the uptake in the human cancers varied between 9 and 43% except for one tissue preparation which had a too low value for measurement. This study shows expression of MAO-A in human pancreatic cancer. This is readily characterised in vitro. The potential use of 11 C-harmine in the diagnosis of pancreatic cancer using PET might be limited, but further PET studies are necessary. (orig.)

  2. BP-C1 in the treatment of patients with stage IV breast cancer: a randomized, double-blind, placebo-controlled multicenter study and an additional open-label treatment phase

    Directory of Open Access Journals (Sweden)

    Larsen S

    2014-11-01

    screening and after every 16 days of treatment. Computed tomography was performed at screening and every 32 days.Results: The sum of target lesions increased 2.4% in the BP-C1 group and 14.3% in the placebo group. Only the increase in the placebo group was significant (P=0.013. The difference between the groups was significant in favor of BP-C1 (P=0.04. There was a significant difference (P=0.026 in favor of BP-C1 regarding Response Evaluation Criteria In Solid Tumors (RECIST classification. The sum of lesions increased slightly in the patients receiving 64 days of continuous BP-C1 treatment, of whom 68.4% were classified as responders. The sum CTC-NCI toxicity score increased nonsignificantly in the BP-C1 group but significantly in the placebo group (P=0.05. The difference in increase between groups did not meet the level of significance (P=0.12. The sum toxicity score was reduced in the patients receiving 64 days of BP-C1 from 9.2 at screening to 8.9 at Day 48, but it increased again to 10.1 by Day 64 and 10.6 during the 28-day follow-up. "Breast cancer-related pain and discomfort" and "Breast cancer treatment problem last week" were significantly reduced (P=0.02 in the BP-C1 group but increased slightly in the placebo group; between-group differences were significant in favor of BP-C1 (P=0.05. "Breast cancer related pain and discomfort", "Breast cancer treatment problem last week," and "Physical activity problem" were significantly reduced during the 64 days of BP-C1 treatment (P≤0.05.Conclusion: For patients suffering from stage IV metastatic breast cancer, treatment with BP-C1 reduces cancer growth, is well tolerated, improves quality of life, and produces few adverse events, which were mainly mild and manageable.Keywords: tumor growth reduction, improved Quality of Life, safe, few transient adverse effects

  3. Evolutionary relationships within the human rhinovirus genus: comparison of serotypes 89, 2, and 14

    International Nuclear Information System (INIS)

    Duechler, M.; Skern, T.; Sommergruber, W.; Neubauer, C.; Gruendler, P.; Fogy, I.; Blaas, D.; Kuechler, E.

    1987-01-01

    The complete nucleotide sequence of the genome of human rhinovirus type 89 was determined from the cDNA that had been cloned into Escherichia coli. The genome is 7152 nucleotides long and contains a single large open reading frame of 2164 codons. Translation commences at position 619 and ends 42 nucleotides before the poly(a) tract. The positions of three proteolytic cleavage sites in the polyprotein were determined by N-terminal amino acid sequencing of the capsid proteins; the remainder were predicted from comparisons with other picornaviruses. Extensive similarity between the derived amino acid sequences of human rhinovirus types 89 and 2 was found, whereas the similarity between human rhinovirus types 89 and 14 was considerably less. It is apparent that human rhinoviruses may be more closely related than has been previously thought

  4. Dicty_cDB: Contig-U09376-1 [Dicty_cDB

    Lifescience Database Archive (English)

    Full Text Available 1540 ) S237P6228RD7.T0 PortugueseWaterDog Canis familiar... 44 8.9 1 ( BV422520 )...H211-264C24 in... 44 8.9 1 ( BX294128 ) Zebrafish DNA sequence from clone DKEYP-35F12 in ... 44 8.9 1 ( BV44

  5. Modulation of AKR1C2 by curcumin decreases testosterone production in prostate cancer.

    Science.gov (United States)

    Ide, Hisamitsu; Lu, Yan; Noguchi, Takahiro; Muto, Satoru; Okada, Hiroshi; Kawato, Suguru; Horie, Shigeo

    2018-04-01

    Intratumoral androgen biosynthesis has been recognized as an essential factor of castration-resistant prostate cancer. The present study investigated the effects of curcumin on the inhibition of intracrine androgen synthesis in prostate cancer. Human prostate cancer cell lines, LNCaP and 22Rv1 cells were incubated with or without curcumin after which cell proliferation was measured at 0, 24, 48 and 72 hours, respectively. Prostate tissues from the transgenic adenocarcinoma of the mouse prostate (TRAMP) model were obtained after 1-month oral administration of 200 mg/kg/d curcumin. Testosterone and dihydrotestosterone concentrations in LNCaP prostate cancer cells were determined through LC-MS/MS assay. Curcumin inhibited cell proliferation and induced apoptosis of prostate cancer cells in a dose-dependent manner. Curcumin decreased the expression of steroidogenic acute regulatory proteins, CYP11A1 and HSD3B2 in prostate cancer cell lines, supporting the decrease of testosterone production. After 1-month oral administration of curcumin, Aldo-Keto reductase 1C2 (AKR1C2) expression was elevated. Simultaneously, decreased testosterone levels in the prostate tissues were observed in the TRAMP mice. Meanwhile, curcumin treatments considerably increased the expression of AKR1C2 in prostate cancer cell lines, supporting the decrease of dihydrotestosterone. Taken together, these results suggest that curcumin's natural bioactive compounds could have potent anticancer properties due to suppression of androgen production, and this could have therapeutic effects on prostate cancer. © 2018 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.

  6. Antecedent characteristics of online cancer information seeking among rural breast cancer patients: an application of the Cognitive-Social Health Information Processing (C-SHIP) model.

    Science.gov (United States)

    Shaw, Bret R; Dubenske, Lori L; Han, Jeong Yeob; Cofta-Woerpel, Ludmila; Bush, Nigel; Gustafson, David H; McTavish, Fiona

    2008-06-01

    Little research has examined the antecedent characteristics of patients most likely to seek online cancer information. This study employs the Cognitive-Social Health Information Processing (C-SHIP) model as a framework to understand what psychosocial characteristics precede online cancer-related information seeking among rural breast cancer patients who often have fewer health care providers and limited local support services. Examining 144 patients who were provided free computer hardware, Internet access, and training for how to use an interactive cancer communication system, pretest survey scores indicating patients' psychosocial status were correlated with specific online cancer information seeking behaviors. Each of the factors specified by the C-SHIP model had significant relationships with online cancer information seeking behaviors, with the strongest findings emerging for cancer-relevant encodings and self-construals, cancer-relevant beliefs and expectancies, and cancer-relevant self-regulatory competencies and skills. Specifically, patients with more negative appraisals in these domains were more likely to seek out online cancer information. Additionally, antecedent variables associated with the C-SHIP model had more frequent relationships with experiential information as compared with to didactic information. This study supports the applicability of the model to discern why people afflicted with cancer may seek online information to cope with their disease.

  7. Antecedent Characteristics of Online Cancer Information Seeking Among Rural Breast Cancer Patients: An Application of the Cognitive-Social Health Information Processing (C-SHIP) Model

    Science.gov (United States)

    Shaw, Bret R.; DuBenske, Lori L.; Han, Jeong Yeob; Cofta-Woerpel, Ludmila; Bush, Nigel; Gustafson, David H.; McTavish, Fiona

    2013-01-01

    Little research has examined the antecedent characteristics of patients most likely to seek online cancer information. This study employs the Cognitive-Social Health Information Processing (C-SHIP) model as a framework to understand what psychosocial characteristics precede online cancer-related information seeking among rural breast cancer patients who often have fewer healthcare providers and limited local support services. Examining 144 patients who were provided free computer hardware, Internet access and training for how to use an Interactive Cancer Communication System, pre-test survey scores indicating patients’ psychosocial status were correlated with specific online cancer information seeking behaviors. Each of the factors specified by the C-SHIP model had significant relationships with online cancer information seeking behaviors with the strongest findings emerging for cancer-relevant encodings and self-construals, cancer-relevant beliefs and expectancies and cancer-relevant self-regulatory competencies and skills. Specifically, patients with more negative appraisals in these domains were more likely to seek out online cancer information. Additionally, antecedent variables associated with the C-SHIP model had more frequent relationships with experiential information as compared to didactic information. This study supports the applicability of the model to discern why people afflicted with cancer may seek online information to cope with their disease. PMID:18569368

  8. A peristaltic pump driven 89Zr separation module

    DEFF Research Database (Denmark)

    Siikanen, J.; Peterson, M.; Tran, T.

    2012-01-01

    To facilitate the separation of 89Zr produced in yttrium foils, an automated separation module was designed and assembled. The module separates more than 85% of produced 89Zr - activity in 3 g foils in less than 90 min. About 10 % remains in the dissolving vial. The quality of the separated 89Zr...

  9. Comparing morbidity and cancer control after 3D-conformal (70/74 Gy) and intensity modulated radiotherapy (78/82 Gy) for prostate cancer

    International Nuclear Information System (INIS)

    Dolezel, Martin; Odrazka, Karel; Zouhar, Milan; Jansa, Jan; Paluska, Petr; Vaculikova, Miloslava; Sefrova, Jana; Kohlova, Tereza; Vanasek, Jaroslav; Kovarik, Josef

    2015-01-01

    The purpose of this work was to compare toxicity and cancer control between patients with prostate cancer treated using three-dimensional conformal radiotherapy (3D-CRT) and those treated using intensity-modulated radiation therapy (IMRT). A total of 553 patients with prostate cancer were treated with 3D-CRT 70-74 Gy (3D-CRT 70, 3D-CRT 74) or IMRT 78-82 Gy (IMRT 78, IMRT/SIB 82). Late toxicity was scored according to FC-RTOG/LENT criteria. Biochemical failure was defined using the Phoenix and ASTRO definitions. The 5-year risk of grade 2-4 genitourinary toxicity was 26.3 % (3D-CRT 70), 27.2 % (3D-CRT 74), 17.3 % (IMRT 78), and 25.1 % (IMRT/SIB 82) without statistical differences. The 5-year risk of grade 2-4 gastrointestinal toxicity was 19.4 % (3D-CRT 70), 42.1 % (3D-CRT 74), 20.5 % (IMRT 78), and 26.6 % (IMRT/SIB 82). The differences between 3D-CRT 74 and 3D-CRT 70 and between 3D-CRT 74 and IMRT 78 were statistically significant (log rank p = 0.03). The 5-year Phoenix PSA relapse-free survival (PSA-RFS) in low-risk, intermediate-risk, and high-risk patients treated using 3D-CRT were 89.4, 65.5, and 57.8 %, respectively. Patients treated with IMRT achieved the following results: 90.9, 89.4, and 83.9 %. Clinical relapse-free survival (C-RFS) in patients treated using 3D-CRT vs. IMRT for the aforementioned groups were 94.7 vs. 100 %, 86.8 vs. 98.6 %, and 84.4 vs. 94.5 %. Disease-free survival (DFS) for patients treated using 3D-CRT were 83.1, 70.9, and 71.5 %. The IMRT group reached 95.8, 89.1, and 87.6 %. The PSA-RFS for intermediate- and high-risk patients were statistically significant, while C-RFS and DFS were marginally better. Dose escalation with IMRT was associated with improved cancer control in intermediate- and high-risk patients in comparison with 3D-CRT, without compromising toxicity. (orig.) [de

  10. Predictive role of the overexpression for CXCR4, C-Met, and VEGF-C among breast cancer patients: A meta-analysis.

    Science.gov (United States)

    Wang, Fang; Li, Shanshan; Zhao, Yueguang; Yang, Kunxian; Chen, Minju; Niu, Heng; Yang, Jingyu; Luo, Ying; Tang, Wenru; Sheng, Miaomiao

    2016-08-01

    The overexpression of CXCR4, C-Met and VEGF-C present widely in breast tumors, they may be markers of resistance to treatment. However, the studies are still controversial. Thus, this meta-analysis aims to research the relationship between the overexpression of CXCR4, C-Met, VEGF-C and clinical prognosis among breast cancer patients. PubMed and EMBASE databases were searched for eligible literature. The outcomes of interest were progression-free survival (PFS), relapse-free survival (RFS) and overall survival (OS). All tests of statistical significance were two sided. A total of 7830 patients from 28 eligible studies were assessed. The overexpression of the CXCR4 and C-Met both implied significantly worse PFS compared with normal expression [HR = 2.56, 95% CI = 1.34-4.91, P = 0.005; and HR = 1.63 95% CI = 1.20-2.22, P = 0.002]. Meanwhile, if patients had high expression of CXCR4, they would have worse OS [HR = 2.56 95% CI = 1.52-4.31, P = 0.000]. However, the overexpression of C-Met did not relate to OS for breast cancer patients [HR = 1.16, 95% CI = 0.69-1.95, P = 0.570]. Meanwhile, no statistically significant different was observed with respect to PFS and OS between VEGF-C overexpression and normal expression [HR = 0.99, 95% CI = 0.64-1.52, P = 0.968; and HR = 0.76, 95% CI = 0.43-1.33, P = 0.333]. Our meta-analysis showed that CXCR4 and C-Met were efficient prognostic factors for breast cancer. Nevertheless, highly expressing VEGF-C was not related to progression-free survival and overall survival. Due to the small samples and insufficient date, further studies should be conducted to clarify the association between the overexpression of CXCR4 or C-Met or VEGF-C and the prognosis about breast cancer patients. Copyright © 2016 Elsevier Ltd. All rights reserved.

  11. Paget's disease of the vulva: A review of 89 cases

    Directory of Open Access Journals (Sweden)

    Cherry O. Onaiwu

    2017-02-01

    Full Text Available The purpose of this study was to retrospectively review the clinical characteristics and outcomes of a series of women with Paget's disease of the vulva. A retrospective review was performed of 89 women with Paget's disease of the vulva evaluated at a single institution between 1966 and 2010. Medical records were reviewed for demographic information, clinical data, pathologic findings, treatment modalities and outcomes. We found that the primary treatment was surgery for 74 (83.1% patients, with positive margins noted in 70.1% of cases. Five patients (5.6% underwent topical treatment with imiquimod and/or 5-fluorouracil, one patient (1.1% underwent laser ablation and treatment was unknown in 9 patients (10.1%. The majority of patients had multiple recurrences, with 18% having four or more recurrences. There were no significant differences in recurrence rates between patients who underwent surgery and those who did not. Furthermore, there was no association between positive margins following primary surgery and recurrence. Forty-one patients (46.1% were diagnosed with 53 synchronous or metachronous cancers. Seven patients (7.9% were found to have invasive vulvar cancer with 1 mm or more depth of invasion, but none of the patients died of Paget's disease or associated vulvar/vaginal cancer. Our findings suggest that the majority of patients with Paget's disease of the vulva develop multiple recurrences regardless of treatment modality or margin status. Alternatives to surgery are needed to better care for women with this disease.

  12. 4 CFR 28.89 - Attorney's fees and costs.

    Science.gov (United States)

    2010-01-01

    ... 4 Accounts 1 2010-01-01 2010-01-01 false Attorney's fees and costs. 28.89 Section 28.89 Accounts... Procedures Board Decisions, Attorney's Fees and Judicial Review § 28.89 Attorney's fees and costs. Within 20... party, may submit a request for the award of reasonable attorney's fees and costs. GAO may file a...

  13. Lanatoside C inhibits cell proliferation and induces apoptosis through attenuating Wnt/β-catenin/c-Myc signaling pathway in human gastric cancer cell.

    Science.gov (United States)

    Hu, Yudong; Yu, Kaikai; Wang, Gang; Zhang, Depeng; Shi, Chaoji; Ding, Yunhe; Hong, Duo; Zhang, Dan; He, Huiqiong; Sun, Lei; Zheng, Jun-Nian; Sun, Shuyang; Qian, Feng

    2018-04-01

    Gastric cancer is the third common cause of cancer mortality in the world with poor prognosis and high recurrence due to lack of effective medicines. Our studies revealed that lanatoside C, a FDA-approved cardiac glycoside, had an anti-proliferation effect on different human cancer cell lines (MKN-45; SGC-7901; HN4; MCF-7; HepG2) and gastric cell lines MKN-45 and SGC-7901 were the most sensitive cell lines to lanatoside C. MKN-45 cells treated with lanatoside C showed cell cycle arrest at G2/M phase and inhibition of cell migration. Meanwhile, upregulation of cleaved caspase-9 and cleaved PARP and downregulation of Bcl-xl were accompanied with the loss of mitochondrial membrane potential (MMP) and induction of intracellular reactive oxygen species (ROS). Lanatoside C inhibited Wnt/β-catenin signaling with downregulation of c-Myc, while overexpression of c-Myc reversed the anti-tumor effect of lanatoside C, confirming that c-Myc is a key drug target of lanatoside C. Furthermore, we discovered that lanatoside C prompted c-Myc degradation in proteasome-ubiquitin pathway with attenuating the binding of USP28 to c-Myc. These findings indicate that lanatoside C targeted c-Myc ubiquitination to inhibit MKN-45 proliferation and support the potential value of lanatoside C as a chemotherapeutic candidate. Copyright © 2018 Elsevier Inc. All rights reserved.

  14. Breast cancer treatment by nanophotolysis approach

    Science.gov (United States)

    Ashiq, Muhammad Gul Bahar

    2018-06-01

    In this work, gold nanoparticles irradiated with nanosecond short pulse laser for breast cancer treatment is studied theoretically. Nanophotolysis is involved for selective damaging of breast cancer cells. Results shows that laser fluence of 1.5 J/cm2 interact with gold nanoparticles and generates a maximum number of ions. Laser light in the visible region interacts with the gold foil. At 700 nm, 12 × 1012 ions are produced for the laser intensity of 8.89 × 107 W/cm2. Slow increase in the Coulomb explosion pressure from 0.6 × 106 Pa to 2 × 106 Pa is observed for a cluster size of range 10 nm to 20 nm. Penetration of nanobullets in tumor increases with the increase of temperature from 39.83 °C to 62.20 °C. Number of cell damaged increases by increasing the number of ions (6 × 1016 cells are damaged by 9.59 × 1020 gold ions). Findings are compared with the other experimental results and are found in excellent agreement. It is concluded from current work that nanophotolysis therapy is may be useful in future for selective damaging of breast cancer cells.

  15. Association between protein C levels and mortality in patients with advanced prostate, lung and pancreatic cancer.

    Science.gov (United States)

    Wilts, I T; Hutten, B A; Meijers, J C M; Spek, C A; Büller, H R; Kamphuisen, P W

    2017-06-01

    Procoagulant factors promote cancer progression and metastasis. Protein C is involved in hemostasis, inflammation and signal transduction, and has a protective effect on the endothelial barrier. In mice, administration of activated protein C reduced experimental metastasis. We assessed the association between protein C and mortality in patients with three types of cancer. The study population consisted of patients with advanced prostate, non-small cell lung or pancreatic cancer, who participated in the INPACT trial (NCT00312013). The trial evaluated the addition of nadroparin to chemotherapy in patients with advanced malignancy. Patients were divided into tertiles based on protein C at baseline. The association between protein C levels and mortality was evaluated with Cox proportional hazard models. We analysed 477 patients (protein C tertiles: C level was 107% (IQR 92-129). In the lowest tertile, 75 patients per 100 patient-years died, as compared to 60 and 54 in the middle and high tertile, respectively. Lower levels of protein C were associated with increased mortality (in tertiles: HR for trend 1.18, 95%CI 1.02-1.36, adjusted for age, sex and nadroparin use; as a continuous variable: HR 1.004, 95%CI 1.00-1.008, p=0.07). Protein C seems inversely associated with mortality in patients with advanced prostate, lung and pancreatic cancer. Further research should validate protein C as a biomarker for mortality, and explore the effects of protein C on progression of cancer. Copyright © 2017 Elsevier Ltd. All rights reserved.

  16. Altered deoxyribonuclease activity in cancer cells and its role in non toxic adjuvant cancer therapy with mixed vitamins C and K3.

    Science.gov (United States)

    Taper, Henryk S

    2008-01-01

    The alterations of deoxyribonuclease DNase activity in cancer cells were the basis of the utilization of mixed vitamins C and K3 in a nontoxic, adjuvant cancer therapy. In order to localize exactly the altered activities of DNase in cancer cells, histochemical methods were utilized. The deficiency of alkaline and acid DNase activity appeared to be characteristic for non-necrotic cells of malignant human and animal tumors. This enzymatic deficiency appeared in experimental carcinogenesis before the phenotypic signs of malignancy. Tumor promoters directly reduced the activity of both DNases. The incidence of spontaneous malignant human and animal tumors appeared to be inversely proportional to the intensity of the activity of both DNases in normal cells and tissues from which these tumors were derived. The fact that alkaline and acid DNase activity was reactivated during the spontaneous and therapeutically induced necrosis of cancer cells suggests that this enzymatic deficiency of DNase activity in cancer cells was due to the action of specific inhibitors of DNases. Characteristic variations of serum alkaline DNase activity in positive responders to therapy, examined in more than 800 cancer-bearing patients, may be the basis for the development of a useful test for therapeutic prognosis and for monitoring of cancer bearing patients. Acid DNase was selectively reactivated in malignant tumor cells by vitamin C (sodium ascorbate), whereas alkaline DNase was reactivated by vitamin K3. Joint vitamin C and K3 administration produced in vitro and in vivo tumor growth inhibition, potentiation and sensitization of chemo- and/or radiotherapy and a decrease in the number of metastases in animals with experimental tumors. Joint vitamin C and K3 administration may be considered as a possible new, non-toxic, adjuvant cancer therapy, which can be easily introduced into the classic protocols of clinical cancer therapy without any supplementary risk for patients.

  17. Hsa-miR-34b/c rs4938723 T>C and hsa-miR-423 rs6505162 C>A polymorphisms are associated with the risk of esophageal cancer in a Chinese population.

    Directory of Open Access Journals (Sweden)

    Jun Yin

    Full Text Available Esophageal cancer is the eighth most common cancer and sixth leading cause of cancer associated death worldwide. Besides environmental risk factors, genetic factors might play an important role in the esophageal cancer carcinogenesis. We conducted a hospital based case-control study to evaluate the genetic susceptibility of functional single nucleotide polymorphisms (SNPs in the microRNAs on the development of esophageal cancer. A total of 629 esophageal squamous cell carcinoma (ESCC cases and 686 controls were recruited for this study. The hsa-miR-34b/c rs4938723 T>C, pri-miR-124-1 rs531564 C>G, pre-miR-125a rs12975333 G>T and hsa-miR-423 rs6505162 C>A genotypes were determined using Ligation Detection Reaction (LDR method. Our results demonstrated that hsa-miR-34b/c rs4938723 CC genotype had a decreased risk of ESCC. The association was evident among patients who never drinking. Hsa-miR-423 rs6505162 C>A might associated with a significantly increased risk of ESCC in patients who smoking. These findings indicated that functional polymorphisms hsa-miR-34b/c rs4938723 T>C and hsa-miR-423 rs6505162 C>A might alter individual susceptibility to ESCC. However, our results were obtained with a limited sample size. Future larger studies with other ethnic populations are required to confirm current findings.

  18. -765 G>C POLYMORPHISM OF THE COX-2 GENE AND GASTRIC CANCER RISK IN BRAZILIAN POPULATION

    Directory of Open Access Journals (Sweden)

    Vanessa Maria de Lima Pazine CAMPANHOLO

    2014-04-01

    Full Text Available Context Genomic alterations play important roles in gastric cancer carcinogenesis. Cyclooxygenases (COX are important enzymes in the maintenance of mucosal integrity and in pathological processes, mainly in inflammation and cancer. The -765G>C COX-2 polymorphism has been implicated in gastric cancer risk. Objectives To evaluate the COX-2 gene polymorphism as a predictor of gastric cancer risk. Methods One hundred gastric cancer patients and 150 controls were enrolled from a Brazilian centre. Personal data regarding related risk factors, including alcohol consumption and smoking behavior, were collected via questionnaire. DNA was extracted from peripheral blood and the genotypes were analyzed using PCR-restriction fragment length polymorphism. Results G/G, G/C and C/C genotypes frequencies was 42.7%, 50% and 7.3%, respectively in controls and 59.0%, 34.0% and 7.0% in gastric cancer. The frequency of the genotypes differed between the groups (P = 0.033. A higher risk of gastric cancer was associated with COX-2 -765G/G genotype (P = 0.048; OR:1.98, 95% CI = 1.01-3.90. Alcohol consumption and smoking in patients with -765G/G genotype also increased the risk of gastric cancer. Conclusions The -765G/G genotype and the -765G allele had been associated with an increased risk for gastric cancer. The presence of smoking and alcohol consumption increased the risk for gastric cancer in subjects with -765G/G genotype compared with the control group. Polymorphism of COX-2 gene and gastric cancer risk.

  19. Clinical survey of prostate cancer

    International Nuclear Information System (INIS)

    Takada, Tsuyoshi; Hatano, Koji; Satoh, Mototaka; Tsujimoto, Yuichi; Honda, Masahito; Matsumiya, Kiyomi; Fujioka, Hideki

    2007-01-01

    Treatment trends and outcomes for prostate cancer in our hospital were reported. A total of 482 patients with prostate cancer treated in our hospital between January, 1990 and December, 2004. The age distribution was from 51 to 99 years-old, with the mean age of 72.9 years-old at onset. The number of prostate cancer patients, especially asymptomatic patients with prostatic specific antigen (PSA) elevation, have increased recently. As for the clinical stage, 92 cases (19.1%), 238 cases (49.4%), 48 cases (10.0%) and 104 cases (21.6%) were stage A, B, C and D, respectively. 425 cases (88.2%) received some form of endocrine therapy. Retropubic prostatectomy or external beam radiation therapy was performed in 77 and 57 cases, respectively all cases. The cause-specific 5-year survival rate of the 482 cases was 79.7%, comprising 100% for stage A1, 96.8% for stage A2, 89.4% for stage B, 79.9% for stage C and 42.9% for stage D. The cause-specific 5-year survival was significantly better in the latter patients (1997-2004) than the former patients (1990-1996) in stage C (p=0.0226), D (p=0.0448). In stage C patients, the retropubic prostatectomy (with endocrine therapy) group, increased in the latter period and showed longer cause-specific 5-year survival than the endocrine therapy group (p=0.0027). In stage D2 patients, chemo-endocrine therapy with etoposide (VP-16), adriamycin (ADM) and cisplatin (CDDP) refractory and cause-specific 5-year survival was longer than endocrine therapy alone (p=0.0467, P=0.0381). Our results suggest that retropubic prostatectomy with endocrine therapy and chemo-endocrine therapy are useful for stage C and D prostate cancer patients, respectively. (author)

  20. Association of microRNA-200c expression levels with clinicopathological factors and prognosis in endometrioid endometrial cancer.

    Science.gov (United States)

    Wilczynski, Milosz; Danielska, Justyna; Domanska-Senderowska, Daria; Dzieniecka, Monika; Szymanska, Bozena; Malinowski, Andrzej

    2018-05-01

    MicroRNAs (miRNAs) are regulators of gene expression, which play an important role in many critical cellular processes including apoptosis, proliferation and cell differentiation. Aberrant miRNA expression has been reported in a variety of human malignancies. Therefore, miRNAs may be potentially used as cancer biomarkers. miRNA-200c, which is a member of the miRNA-200 family, might play an essential role in tumor progression. The purpose of this study was to evaluate the prognostic and clinical significance of miRNA-200c in women with endometrioid endometrial cancer. Total RNA extraction from 90 archival formalin-fixed paraffin-embedded tissue samples of endometri-oid endometrial cancer and 10 normal endometrium samples was performed. After cDNA synthesis, real-time polymerase chain reaction was conducted and relative expression of miRNA-200c was assessed. Then, miRNA-200c expression levels were evaluated with regard to clinicopathological characteristics. The expression levels of miRNA-200c were significantly increased in endometrioid endometrial cancer samples. Expression of miRNA-200c maintained at significantly higher levels in the early stage endometrioid endometrial cancer compared with more advanced stages. In the Kaplan-Meier analysis, lower levels of miRNA-200c expression were associated with inferior survival. Expression levels of miRNA-200c might be associated with clinicopathological factors and survival in endometrioid endometrial cancer. © 2018 Nordic Federation of Societies of Obstetrics and Gynecology.

  1. Low-Dose-Rate Brachytherapy Versus Cryotherapy in Low- and Intermediate-Risk Prostate Cancer

    International Nuclear Information System (INIS)

    Gestaut, Matthew M.; Cai, Wendi; Vyas, Shilpa; Patel, Belur J.; Hasan, Salman A.; MunozMaldonado, Yolanda; Deb, Niloyjyoti; Swanson, Gregory

    2017-01-01

    Purpose: Cryotherapy and brachytherapy are definitive local treatment options for low- to intermediate-risk prostate cancer. There are both prospective and retrospective data for brachytherapy, but the use of cryotherapy has been limited primarily to single-institution retrospective studies. Currently, no published evidence has compared low-dose-rate brachytherapy versus cryotherapy. Methods and Materials: Institutional review board approval was obtained to conduct a retrospective chart review of consecutive patients treated at our institution from 1990 to 2012. For inclusion, patients must have received a prostate cancer diagnosis and have been considered to have low- to intermediate-risk disease according to the National Comprehensive Cancer Network criteria. All patients received brachytherapy or cryotherapy treatment. Disease specifics and failure details were collected for all patients. Failure was defined as prostate-specific antigen nadir +2 ng/mL. Results: A total of 359 patients were analyzed. The groups comprised 50 low-risk cryotherapy (LRC), 92 intermediate-risk cryotherapy (IRC), 133 low-risk brachytherapy (LRB), and 84 intermediate-risk brachytherapy (IRB) patients. The median prostate-specific antigen follow-up periods were 85.6 months (LRC), 59.2 months (IRC), 74.9 months (LRB), and 59.8 months (IRB). The 5-year biochemical progression–free survival (bPFS) rate was 57.9% in the cryotherapy group versus 89.6% in the brachytherapy group (P<.0001). The 5-year bPFS rate was 70.0% (LRC), 51.4% (IRC), 89.4% (LRB), and 89.7% (IRB). The bPFS rate was significantly different between brachytherapy and cryotherapy for low- and intermediate-risk groups (P<.05). The mean nadir temperature reached for cryotherapy patients was −35°C (range, −96°C to −6°C). Cryotherapy used a median of 2 freeze-thaw cycles (range, 2-4 freeze-thaw cycles). Conclusions: Results from this study suggest that cryotherapy is inferior to brachytherapy for patients with

  2. Low-Dose-Rate Brachytherapy Versus Cryotherapy in Low- and Intermediate-Risk Prostate Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Gestaut, Matthew M., E-mail: Matthew.Gestaut@BSWHealth.org [Department of Radiation Oncology, Baylor Scott and White Memorial Hospital, Texas A& M University School of Medicine, Temple, Texas (United States); Cai, Wendi [Department of Biostatistics, Baylor Scott and White Health, Temple, Texas (United States); Vyas, Shilpa [Department of Radiation Oncology, Swedish Cancer Institute, Seattle, Washington (United States); Patel, Belur J. [Department of Urology, Baylor Scott and White Memorial Hospital, Texas A& M University School of Medicine, Temple, Texas (United States); Hasan, Salman A. [Department of Radiation Oncology, Baylor Scott and White Memorial Hospital, Texas A& M University School of Medicine, Temple, Texas (United States); MunozMaldonado, Yolanda [Department of Biostatistics, Baylor Scott and White Health, Temple, Texas (United States); Deb, Niloyjyoti; Swanson, Gregory [Department of Radiation Oncology, Baylor Scott and White Memorial Hospital, Texas A& M University School of Medicine, Temple, Texas (United States)

    2017-05-01

    Purpose: Cryotherapy and brachytherapy are definitive local treatment options for low- to intermediate-risk prostate cancer. There are both prospective and retrospective data for brachytherapy, but the use of cryotherapy has been limited primarily to single-institution retrospective studies. Currently, no published evidence has compared low-dose-rate brachytherapy versus cryotherapy. Methods and Materials: Institutional review board approval was obtained to conduct a retrospective chart review of consecutive patients treated at our institution from 1990 to 2012. For inclusion, patients must have received a prostate cancer diagnosis and have been considered to have low- to intermediate-risk disease according to the National Comprehensive Cancer Network criteria. All patients received brachytherapy or cryotherapy treatment. Disease specifics and failure details were collected for all patients. Failure was defined as prostate-specific antigen nadir +2 ng/mL. Results: A total of 359 patients were analyzed. The groups comprised 50 low-risk cryotherapy (LRC), 92 intermediate-risk cryotherapy (IRC), 133 low-risk brachytherapy (LRB), and 84 intermediate-risk brachytherapy (IRB) patients. The median prostate-specific antigen follow-up periods were 85.6 months (LRC), 59.2 months (IRC), 74.9 months (LRB), and 59.8 months (IRB). The 5-year biochemical progression–free survival (bPFS) rate was 57.9% in the cryotherapy group versus 89.6% in the brachytherapy group (P<.0001). The 5-year bPFS rate was 70.0% (LRC), 51.4% (IRC), 89.4% (LRB), and 89.7% (IRB). The bPFS rate was significantly different between brachytherapy and cryotherapy for low- and intermediate-risk groups (P<.05). The mean nadir temperature reached for cryotherapy patients was −35°C (range, −96°C to −6°C). Cryotherapy used a median of 2 freeze-thaw cycles (range, 2-4 freeze-thaw cycles). Conclusions: Results from this study suggest that cryotherapy is inferior to brachytherapy for patients with

  3. Tumor Radiation Therapy Creates Therapeutic Vaccine Responses to the Colorectal Cancer Antigen GUCY2C

    Energy Technology Data Exchange (ETDEWEB)

    Witek, Matthew [Department of Radiation Oncology, Kimmel Cancer Center, Jefferson Medical College, Thomas Jefferson University, Philadelphia, Pennsylvania (United States); Blomain, Erik S.; Magee, Michael S.; Xiang, Bo; Waldman, Scott A. [Department of Pharmacology and Experimental Therapeutics, Thomas Jefferson University, Philadelphia, Pennsylvania (United States); Snook, Adam E., E-mail: adam.snook@jefferson.edu [Department of Pharmacology and Experimental Therapeutics, Thomas Jefferson University, Philadelphia, Pennsylvania (United States)

    2014-04-01

    Purpose: Radiation therapy (RT) is thought to produce clinical responses in cancer patients, not only through direct toxicity to cancer cells and supporting tumor stroma cells, but also through activation of immunologic effectors. More recently, RT has potentiated the local and systemic effects of cancer immunotherapy (IT). However, combination regimens that maximize immunologic and clinical efficacy remain undefined. Methods and Materials: We evaluated the impact of local RT on adenoviral-mediated vaccination against the colorectal cancer antigen GUCY2C (Ad5-GUCY2C) in a murine subcutaneous tumor model using mouse CT26 colon cancer cells (CT26-GUCY2C). Immune responses were assessed by ELISpot, and clinical responses were assessed by tumor size and incidence. Results: The specific sequence of tumor-directed RT preceding Ad5-GUCY2C IT transformed inactive therapeutic Ad5-GUCY2C vaccination into a curative vaccine. GUCY2C-specific T cell responses were amplified (P<.05), tumor eradication was maximized (P<.01), and tumor volumes were minimized (P<.001) in mice whose tumors were irradiated before, compared with after, Ad5-GUCY2C vaccination. The immunologic and antitumor efficacy of Ad5-GUCY2C was amplified comparably by unfractionated (8 Gy × 1), or biologically equivalent doses of fractionated (3.5 Gy × 3), RT. The antitumor effects of sequential RT and IT (RT-IT) depended on expression of GUCY2C by tumor cells and the adenoviral vaccine vector, and tumor volumes were inversely related to the magnitude of GUCY2C-specific T cell responses. Moreover, mice cured of CT26-GUCY2C tumors by RT-IT showed long-lasting antigen-dependent protection, resisting tumors formed by GUCY2C-expressing 4T1 breast cancer cells inoculated 50 days after CT26 cells. Conclusions: Optimal sequencing of RT and IT amplifies antigen-specific local and systemic immune responses, revealing novel acute and long-term therapeutic antitumor protection. These observations underscore the importance

  4. Anthracycline resistance mediated by reductive metabolism in cancer cells: The role of aldo-keto reductase 1C3

    International Nuclear Information System (INIS)

    Hofman, Jakub; Malcekova, Beata; Skarka, Adam; Novotna, Eva; Wsol, Vladimir

    2014-01-01

    Pharmacokinetic drug resistance is a serious obstacle that emerges during cancer chemotherapy. In this study, we investigated the possible role of aldo-keto reductase 1C3 (AKR1C3) in the resistance of cancer cells to anthracyclines. First, the reducing activity of AKR1C3 toward anthracyclines was tested using incubations with a purified recombinant enzyme. Furthermore, the intracellular reduction of daunorubicin and idarubicin was examined by employing the transfection of A549, HeLa, MCF7 and HCT 116 cancer cells with an AKR1C3 encoding vector. To investigate the participation of AKR1C3 in anthracycline resistance, we conducted MTT cytotoxicity assays with these cells, and observed that AKR1C3 significantly contributes to the resistance of cancer cells to daunorubicin and idarubicin, whereas this resistance was reversible by the simultaneous administration of 2′-hydroxyflavanone, a specific AKR1C3 inhibitor. In the final part of our work, we tracked the changes in AKR1C3 expression after anthracycline exposure. Interestingly, a reciprocal correlation between the extent of induction and endogenous levels of AKR1C3 was recorded in particular cell lines. Therefore, we suggest that the induction of AKR1C3 following exposure to daunorubicin and idarubicin, which seems to be dependent on endogenous AKR1C3 expression, eventually might potentiate an intrinsic resistance given by the normal expression of AKR1C3. In conclusion, our data suggest a substantial impact of AKR1C3 on the metabolism of daunorubicin and idarubicin, which affects their pharmacokinetic and pharmacodynamic behavior. In addition, we demonstrate that the reduction of daunorubicin and idarubicin, which is catalyzed by AKR1C3, contributes to the resistance of cancer cells to anthracycline treatment. - Highlights: • Metabolism of anthracyclines by AKR1C3 was studied at enzyme and cellular levels. • Anthracycline resistance mediated by AKR1C3 was demonstrated in cancer cells. • Induction of AKR1C3

  5. Hyperhomocysteinemia, methylenetetrahydrofolate reductase c.677C>T polymorphism and risk of cancer: cross-sectional and prospective studies and meta-analyses of 75,000 cases and 93,000 controls

    DEFF Research Database (Denmark)

    Zacho, Jeppe; Yazdanyar, Shiva; Bojesen, Stig E

    2011-01-01

    including 74,671 cases and 93,344 controls. Cross-sectionally, plasma homocysteine levels were 12.9 and 11.6 µmol/L in those with and without cancer (p homocysteine levels increased with age and age-adjusted odds ratio for any cancer in those with homocysteine levels >12.4 versus ....4 µmol/L did not differ from 1.0. In cancer-free participants, plasma homocysteine levels were 14.7 and 11.7 µmol/L in MTHFR c.677C>T homozygtes and noncarriers (p T homozygotes versus noncarriers did not differ...... from 1.0. However, in meta-analyses odds ratio for MTHFR c.677C>T homozygotes versus noncarriers were 1.07 (95% CI: 1.01-1.12) for any cancer, 1.77 (1.17-2.68) for esophagus cancer, 1.40 (1.19-1.66) for gastric cancer and 0.85 (0.77-0.94) for colorectal cancer. Increased plasma homocysteine levels...

  6. 49 CFR 393.89 - Buses, driveshaft protection.

    Science.gov (United States)

    2010-10-01

    ... ACCESSORIES NECESSARY FOR SAFE OPERATION Miscellaneous Parts and Accessories § 393.89 Buses, driveshaft protection. Any driveshaft extending lengthways under the floor of the passenger compartment of a bus shall... 49 Transportation 5 2010-10-01 2010-10-01 false Buses, driveshaft protection. 393.89 Section 393...

  7. 40 CFR 89.317 - NOX converter check.

    Science.gov (United States)

    2010-07-01

    ... 40 Protection of Environment 20 2010-07-01 2010-07-01 false NOX converter check. 89.317 Section 89.317 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR PROGRAMS (CONTINUED..., the chemiluminescent oxides of nitrogen analyzer shall be checked for NO2 to NO converter efficiency...

  8. 40 CFR 89.105 - Certificate of conformity.

    Science.gov (United States)

    2010-07-01

    ... 40 Protection of Environment 20 2010-07-01 2010-07-01 false Certificate of conformity. 89.105... and Certification Provisions § 89.105 Certificate of conformity. Every manufacturer of a new nonroad compression-ignition engine must obtain a certificate of conformity covering the engine family, as described...

  9. The Multifunctional Protein Kinase C-ε in Cancer Development and Progression

    Science.gov (United States)

    Jain, Kirti; Basu, Alakananda

    2014-01-01

    The protein kinase C (PKC) family proteins are important signal transducers and have long been the focus of cancer research. PKCɛ, a member of this family, is overexpressed in most solid tumors and plays critical roles in different processes that lead to cancer development. Studies using cell lines and animal models demonstrated the transforming potential of PKCɛ. While earlier research established the survival functions of PKCɛ, recent studies revealed its role in cell migration, invasion and cancer metastasis. PKCɛ has also been implicated in epithelial to mesenchymal transition (EMT), which may be the underlying mechanism by which it contributes to cell motility. In addition, PKCɛ affects cell-extracellular matrix (ECM) interactions by direct regulation of the cytoskeletal elements. Recent studies have also linked PKCɛ signaling to cancer stem cell functioning. This review focuses on the role of PKCɛ in different processes that lead to cancer development and progression. We also discussed current literatures on the pursuit of PKCɛ as a target for cancer therapy. PMID:24727247

  10. The Multifunctional Protein Kinase C-ε in Cancer Development and Progression

    Directory of Open Access Journals (Sweden)

    Kirti Jain

    2014-04-01

    Full Text Available The protein kinase C (PKC family proteins are important signal transducers and have long been the focus of cancer research. PKCɛ, a member of this family, is overexpressed in most solid tumors and plays critical roles in different processes that lead to cancer development. Studies using cell lines and animal models demonstrated the transforming potential of PKCɛ. While earlier research established the survival functions of PKCɛ, recent studies revealed its role in cell migration, invasion and cancer metastasis. PKCɛ has also been implicated in epithelial to mesenchymal transition (EMT, which may be the underlying mechanism by which it contributes to cell motility. In addition, PKCɛ affects cell-extracellular matrix (ECM interactions by direct regulation of the cytoskeletal elements. Recent studies have also linked PKCɛ signaling to cancer stem cell functioning. This review focuses on the role of PKCɛ in different processes that lead to cancer development and progression. We also discussed current literatures on the pursuit of PKCɛ as a target for cancer therapy.

  11. The Multifunctional Protein Kinase C-ε in Cancer Development and Progression

    International Nuclear Information System (INIS)

    Jain, Kirti; Basu, Alakananda

    2014-01-01

    The protein kinase C (PKC) family proteins are important signal transducers and have long been the focus of cancer research. PKCε, a member of this family, is overexpressed in most solid tumors and plays critical roles in different processes that lead to cancer development. Studies using cell lines and animal models demonstrated the transforming potential of PKCε. While earlier research established the survival functions of PKCε, recent studies revealed its role in cell migration, invasion and cancer metastasis. PKCε has also been implicated in epithelial to mesenchymal transition (EMT), which may be the underlying mechanism by which it contributes to cell motility. In addition, PKCε affects cell-extracellular matrix (ECM) interactions by direct regulation of the cytoskeletal elements. Recent studies have also linked PKCε signaling to cancer stem cell functioning. This review focuses on the role of PKCε in different processes that lead to cancer development and progression. We also discussed current literatures on the pursuit of PKCε as a target for cancer therapy.

  12. The Multifunctional Protein Kinase C-ε in Cancer Development and Progression

    Energy Technology Data Exchange (ETDEWEB)

    Jain, Kirti; Basu, Alakananda, E-mail: alakananda.basu@unthsc.edu [Department of Molecular and Medical Genetics, University of North Texas Health Science Center, Institute for Cancer Research, and Focused on Resources for her Health Education and Research, Fort Worth, TX 76107 (United States)

    2014-04-10

    The protein kinase C (PKC) family proteins are important signal transducers and have long been the focus of cancer research. PKCε, a member of this family, is overexpressed in most solid tumors and plays critical roles in different processes that lead to cancer development. Studies using cell lines and animal models demonstrated the transforming potential of PKCε. While earlier research established the survival functions of PKCε, recent studies revealed its role in cell migration, invasion and cancer metastasis. PKCε has also been implicated in epithelial to mesenchymal transition (EMT), which may be the underlying mechanism by which it contributes to cell motility. In addition, PKCε affects cell-extracellular matrix (ECM) interactions by direct regulation of the cytoskeletal elements. Recent studies have also linked PKCε signaling to cancer stem cell functioning. This review focuses on the role of PKCε in different processes that lead to cancer development and progression. We also discussed current literatures on the pursuit of PKCε as a target for cancer therapy.

  13. ATM kinase sustains breast cancer stem-like cells by promoting ATG4C expression and autophagy.

    Science.gov (United States)

    Antonelli, Martina; Strappazzon, Flavie; Arisi, Ivan; Brandi, Rossella; D'Onofrio, Mara; Sambucci, Manolo; Manic, Gwenola; Vitale, Ilio; Barilà, Daniela; Stagni, Venturina

    2017-03-28

    The efficacy of Ataxia-Telangiectasia Mutated (ATM) kinase signalling inhibition in cancer therapy is tempered by the identification of new emerging functions of ATM, which suggests that the role of this protein in cancer progression is complex. We recently demonstrated that this tumor suppressor gene could act as tumor promoting factor in HER2 (Human Epidermal Growth Factor Receptor 2) positive breast cancer. Herein we put in evidence that ATM expression sustains the proportion of cells with a stem-like phenotype, measured as the capability to form mammospheres, independently of HER2 expression levels. Transcriptomic analyses revealed that, in mammospheres, ATM modulates the expression of cell cycle-, DNA repair- and autophagy-related genes. Among these, the silencing of the autophagic gene, autophagy related 4C cysteine peptidase (ATG4C), impairs mammosphere formation similarly to ATM depletion. Conversely, ATG4C ectopic expression in cells silenced for ATM expression, rescues mammospheres growth. Finally, tumor array analyses, performed using public data, identify a significant correlation between ATM and ATG4C expression levels in all human breast cancer subtypes, except for the basal-like one.Overall, we uncover a new connection between ATM kinase and autophagy regulation in breast cancer. We demonstrate that, in breast cancer cells, ATM and ATG4C are essential drivers of mammosphere formation, suggesting that their targeting may improve current approaches to eradicate breast cancer cells with a stem-like phenotype.

  14. Trends in lung cancer in elderly in Denmark, 1980-2012

    DEFF Research Database (Denmark)

    Kristiansen, Charlotte; Schytte, Tine; Holmskov, Karin

    2016-01-01

    1980. Due to the poor survival, similar trends were seen in mortality rates. Over the period, the one-year relative survival rates almost doubled in patients aged 70 years or more, but still only 25% of the patients aged 80-89 years survived their lung cancer for one year. Conclusion The incidence...... and methods Lung cancer was defined as ICD-10 codes C33-34. Data derived from the NORDCAN database with comparable data on cancer incidence, mortality, prevalence, and relative survival in the Nordic countries, where the Danish data were delivered from the Danish Cancer Registry and the Danish Cause of Death...... Registry with follow-up for death or emigration until the end of 2013. Results In 2012, about 50% of lung cancers were diagnosed among persons aged 70 years or more. For men and women older than 75 years the incidence rates have been increasing and for those aged 80-84 years, the rates have doubled since...

  15. The accumulation and elimination of 89Sr in tea leaves

    International Nuclear Information System (INIS)

    Zhang Yongxi; Wang Shouxiang; Chen Chuanqun; Sun Zhiming; Hu Bingmin; Huang Dan

    1995-01-01

    The 89 Sr was added to the tea tree-soil system by different ways. The 89 Sr in the system through the over-ground part of tea tree, was much more than that through soil. The 89 Sr concentration in older leaves was higher than in shoot for a definite treatment. The accumulation elimination law of 89 Sr in leaves varied with the treatments. For the treatment through the over-ground part, the 89 Sr concentration in older leaves and shoot was monotonously decreased with time increasing. But for the treatment through soil the 89 Sr concentration in shoot was increased to reach a peak value, and then decreased slowly; while the 89 Sr concentration in older leaves increased quickly in a period, then increased slowly to attain a saturated value. In addition, the concentration factor of 89 Sr in older leaves and shoot were determined

  16. 40 CFR 89.908 - National security exemption.

    Science.gov (United States)

    2010-07-01

    ... 40 Protection of Environment 20 2010-07-01 2010-07-01 false National security exemption. 89.908... Provisions § 89.908 National security exemption. (a)(1) Any nonroad engine, otherwise subject to this part... regulations for purposes of national security. No request for exemption is necessary. (2) Manufacturers may...

  17. 9 CFR 89.1 - Amount of feed.

    Science.gov (United States)

    2010-01-01

    ... 9 Animals and Animal Products 1 2010-01-01 2010-01-01 false Amount of feed. 89.1 Section 89.1 Animals and Animal Products ANIMAL AND PLANT HEALTH INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE INTERSTATE TRANSPORTATION OF ANIMALS (INCLUDING POULTRY) AND ANIMAL PRODUCTS STATEMENT OF POLICY UNDER THE...

  18. Functions of Tenascin-C and Integrin alpha9beta1 in Mediating Prostate Cancer Bone Metastasis

    Science.gov (United States)

    2017-10-01

    AWARD  NUMBER:          W81XWH-16-1-0523 TITLE:  Functions of Tenascin- C and Integrin alpha9beta1 in Mediating Prostate Cancer Bone Metastasis...Prostat Prostate Cancer  Bone Metastasis   5a.  CONTRACT  NUMBER   Functions of Tenascin- C and Integrin alpha9beta1 in Mediating Prostate Cancer...SUPPLEMENTARY  NOTES 14. ABSTRACT The purpose of this work is to dissect mechanisms responsible for interactions between integrin a9b1 and tenascin- C that are

  19. Phase III study comparing chemotherapy and radiotherapy with preoperative chemotherapy and surgical resection in patients with non-small-cell lung cancer with spread to mediastinal lymph nodes (N2); final report of RTOG 89-01

    International Nuclear Information System (INIS)

    Johnstone, David W.; Byhardt, Roger W.; Ettinger, David; Scott, Charles B.

    2002-01-01

    Purpose: To compare the outcome of treatment of mediastinoscopy-verified N2 non-small-cell lung cancer treated with induction chemotherapy followed by either surgery or radiotherapy (RT), with both options followed by consolidation chemotherapy. Methods and Materials: A randomized Phase III trial for Stage IIIA (T1-T3N2M0) non-small cell lung cancer was conducted by the Radiation Therapy Oncology Group (RTOG) and Eastern Cooperative Oncology Group between April 1990 and April 1994. After documentation of N2 disease by mediastinoscopy or anterior mediastinotomy, patients received induction chemotherapy with cisplatin, vinblastine, and mitomycin-C. Mitomycin-C was later dropped from the induction regimen. Patients were then randomized to surgery or RT (64 Gy in 7 weeks) followed by cisplatin and vinblastine. Results: RTOG 89-01 accrued 75 patients, of whom 73 were eligible and analyzable. Twelve patients received induction chemotherapy but were not randomized to RT or surgery thereafter. Forty-five patients were randomized to postinduction RT or surgery. Of the analyzable patients, 90% had a Karnofsky performance score of 90-100, 18% had weight loss >5%, 37% had squamous cell histologic features, and 54% had bulky N2 disease. The distribution of bulky N2 disease was uniform among the treatment arms. The incidence of Grade 4 toxicity was 56% in patients receiving mitomycin-C and 29% in those who did not. Only 1 patient in each group had acute nonhematologic toxicity greater than Grade 3 (nausea and vomiting). No acute Grade 4 radiation toxicity developed. The incidences of long-term toxicity were equivalent across the arms. Three treatment-related deaths occurred: 2 patients in the surgical arms (one late pulmonary toxicity and one pulmonary embolus), and 1 patient in the radiation arm (radiation pneumonitis). Induction chemotherapy was completed in 78% of the patients. Complete resection was performed in 73% of 26 patients undergoing thoracotomy. Consolidation

  20. C-KIT AND Stem Cell Factor Expression in Breast Cancer

    National Research Council Canada - National Science Library

    Hines, Susan

    1998-01-01

    ...) is seen frequently in breast cancer. The MCF7 cell line (which only expresses SCF) transfected with a c-kit expression vector, shows enhanced growth in serum/free medium supplemented with EGF or lGF1...

  1. 40 CFR 89.325 - Engine intake air temperature measurement.

    Science.gov (United States)

    2010-07-01

    ... 40 Protection of Environment 20 2010-07-01 2010-07-01 false Engine intake air temperature measurement. 89.325 Section 89.325 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR... Test Equipment Provisions § 89.325 Engine intake air temperature measurement. (a) Engine intake air...

  2. 40 CFR 89.321 - Oxides of nitrogen analyzer calibration.

    Science.gov (United States)

    2010-07-01

    ... 40 Protection of Environment 20 2010-07-01 2010-07-01 false Oxides of nitrogen analyzer calibration. 89.321 Section 89.321 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR... Test Equipment Provisions § 89.321 Oxides of nitrogen analyzer calibration. (a) The chemiluminescent...

  3. Integrative Analysis of Complex Cancer Genomics and Clinical Profiles Using the cBioPortal

    Science.gov (United States)

    Gao, Jianjiong; Aksoy, Bülent Arman; Dogrusoz, Ugur; Dresdner, Gideon; Gross, Benjamin; Sumer, S. Onur; Sun, Yichao; Jacobsen, Anders; Sinha, Rileen; Larsson, Erik; Cerami, Ethan; Sander, Chris; Schultz, Nikolaus

    2014-01-01

    The cBioPortal for Cancer Genomics (http://cbioportal.org) provides a Web resource for exploring, visualizing, and analyzing multidimensional cancer genomics data. The portal reduces molecular profiling data from cancer tissues and cell lines into readily understandable genetic, epigenetic, gene expression, and proteomic events. The query interface combined with customized data storage enables researchers to interactively explore genetic alterations across samples, genes, and pathways and, when available in the underlying data, to link these to clinical outcomes. The portal provides graphical summaries of gene-level data from multiple platforms, network visualization and analysis, survival analysis, patient-centric queries, and software programmatic access. The intuitive Web interface of the portal makes complex cancer genomics profiles accessible to researchers and clinicians without requiring bioinformatics expertise, thus facilitating biological discoveries. Here, we provide a practical guide to the analysis and visualization features of the cBioPortal for Cancer Genomics. PMID:23550210

  4. Proteomic profiling of mammary carcinomas identifies C7orf24, a gamma-glutamyl cyclotransferase, as a potential cancer biomarker

    DEFF Research Database (Denmark)

    Gromov, Pavel; Gromova, Irina; Friis, Esbern

    2010-01-01

    Breast cancer is the leading cause of cancer deaths in women today and is the most common cancer (excluding skin cancers) among women in the Western world. Although cancers detected by screening mammography are significantly smaller than nonscreening ones, noninvasive biomarkers for detection......, and a novel protein, C7orf24, was identified as being upregulated in cancer cells. Protein expression levels of C7orf24 were evaluated by immunohistochemical assays to qualify deregulation of this protein. Analysis of C7orf24 expression showed up-regulation in 36.4 and 23.4% of cases present in the discovery...

  5. Design and Implementation of Mobile Car with Wireless Video Monitoring System Based on STC89C52

    Directory of Open Access Journals (Sweden)

    Yang Hong

    2014-05-01

    Full Text Available With the rapid development of wireless networks and image acquisition technology, wireless video transmission technology has been widely applied in various communication systems. The traditional video monitoring technology is restricted by some conditions such as layout, environmental, the relatively large volume, cost, and so on. In view of this problem, this paper proposes a method that the mobile car can be equipped with wireless video monitoring system. The mobile car which has some functions such as detection, video acquisition and wireless data transmission is developed based on STC89C52 Micro Control Unit (MCU and WiFi router. Firstly, information such as image, temperature and humidity is processed by the MCU and communicated with the router, and then returned by the WiFi router to the host computer phone. Secondly, control information issued by the host computer phone is received by WiFi router and sent to the MCU, and then the MCU sends relevant instructions. Lastly, the wireless transmission of video images and the remote control of the car are realized. The results prove that the system has some features such as simple operation, high stability, fast response, low cost, strong flexibility, widely application, and so on. The system has certain practical value and popularization value.

  6. Association between the polymorphisms of urokinase plasminogen activation system and cancer risk: a meta-analysis

    Directory of Open Access Journals (Sweden)

    Xu Z

    2015-09-01

    Full Text Available Zhen Xu,1,* Li-Li Meng,2,* Jizong Lin,3 Yunbiao Ling,3 Shu-xian Chen,3 Nan Lin31Department of Infectious Diseases, The Third Affiliated Hospital, Sun Yat-sen University, 2Department of Gynecology and Obstetrics, Sun Yat-sen Memorial Hospital, 3Department of Hepatobiliary Surgery, The Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, People’s Republic of China *These authors contributed equally to this studyPurpose: The present study aimed to investigate the potential association between the urokinase plasminogen activation (uPA system polymorphisms (rs4065, rs2227564, and rs344781 and cancer risk.Methods: An extensive search was performed to identify published case–control studies on the association between the uPA system polymorphisms and cancer risk. Odds ratios (ORs with 95% confidence intervals (CIs were used to evaluate the relationship between the uPA system polymorphisms and cancer risk.Results: A total of 20 studies comprising 7,037 cancer cases and 10,094 controls were identified and included in the present meta-analysis. Overall, significantly increased cancer risk was associated with the uPA polymorphism rs4065 (T vs C: OR 1.50, 95% CI: 1.19–1.89; TT vs CC: OR 4.63, 95% CI: 3.10–6.91; dominant model: OR 1.93, 95% CI: 1.60–2.33; recessive model: OR 3.02, 95% CI: 1.26–7.25 and the uPA receptor polymorphism rs344781 (T vs C: OR 1.13, 95% CI: 1.04–1.23; TC vs CC: OR 1.26, 95% CI: 1.06–1.49; TT vs CC: OR 1.35, 95% CI: 1.13–1.63; dominant model: OR 1.29, 95% CI: 1.10–1.52. No significant association was found between the uPA polymorphism rs2227564 and cancer risk. Subgroup analysis suggests that the T allele of the rs4065 (T allele vs C allele: OR 1.50, 95% CI: 1.19–1.89 and rs344781 polymorphisms (T allele vs C allele: OR 1.13, 95% CI: 1.04–1.23 was associated with increased cancer risk in Asians.Conclusion: Our results suggest that the uPA polymorphism rs4065 and the uPA receptor polymorphism rs344781

  7. HLA and skin cancer HLA e câncer de pele

    Directory of Open Access Journals (Sweden)

    Renan Rangel Bonamigo

    2012-02-01

    Full Text Available Skin cancer - melanoma and non melanoma - are common neoplasm with rising incidence over the last decades. It is an important public health problem. Its pathogenesis is not completely understood and the same happens with the genetic factors involved. The genes that encode the HLA are associated with some tumors and they may be responsible for one of the mechanisms that take part in the development of the before mentioned cancers. We have reviewed the literature on the subject of HLA antigens, melanoma and non melanoma skin cancer.Os cânceres da pele - melanoma e não-melanoma - são neoplasias comuns e com incidência crescente ao longo de décadas. Representam um importante problema de saúde pública. A patogênese destas neoplasias não é completamente compreendida, assim como não o são os fatores genéticos envolvidos. Os genes HLA estão associados a alguns tumores e podem representar um dos mecanismos implicados no desenvolvimento do câncer de pele. Apresenta-se uma revisão atualizada sobre a relação entre antígenos HLA, câncer da pele não-melanoma e melanoma.

  8. Second cancers following radiotherapy for cervical cancer

    International Nuclear Information System (INIS)

    Kleinerman, R.A.; Curtis, R.E.; Boice, J.D. Jr.; Flannery, J.T.; Fraumeni, J.F. Jr.

    1982-01-01

    Incidence of second primary cancers was evaluated in 7,127 women with invasive cancer of the cervix uteri, diagnosed between 1935 and 1978, and followed up to 38 years (average, 8.9 yr) in Connecticut. Among 5,997 women treated with radiation, 449 developed second primary cancers compared with 313 expected (relative risk . 1.4) on the basis of rates from the Connecticut Tumor Registry. Excess incidence was noticeable 15 years or more after radiotherapy and attributed mostly to cancers of sites in or near the radiation field, especially the bladder, kidneys, rectum, corpus uteri, and ovaries. No excess was found for these sites among the 1,130 nonirradiated women. The ratio of observed to expected cancers for these sites did not vary appreciably by age at irradiation. The data suggested that high-dose pelvic irradiation was associated with increase in cancers of the bladder, kidneys, rectum, ovaries, corpus uteri, and non-Hodgkin's lymphoma but, apparently, not leukemia, Hodgkin's disease, breast cancer, or colon cancer

  9. Radiotherapy improves serum fatty acids and lipid profile in breast cancer.

    Science.gov (United States)

    Shaikh, Sana; Channa, Naseem Aslam; Talpur, Farha Naz; Younis, Muhammad; Tabassum, Naila

    2017-05-18

    Breast cancer is a disease with diverse clinical symptoms, molecular profiles, and its nature to response its therapeutic treatments. Radiotherapy (RT), along with surgery and chemotherapy is a part of treatment in breast cancer. The aim of present study was to investigate pre and post treatment effects of radiotherapy in serum fatty acids and its lipids profile in patients with breast cancer. In this comparative as well as follow up study, Serum fatty acids were performed by gas chromatography to investigate fatty acids and Microlab for analysis of lipid profile. Among serum free and total fatty acids the major saturated fatty acids (SFAs) in serum lipids of breast cancer patients (pre and post treated) were stearic acid (18:0) and palmitic acid (16:0). These fatty acids contributed about 35-50% of total fatty acids. The decreased concentrations of linoleic acid (C18:2) and arachidonic acid (C20:4) with a lower ratio of C18:2/C18:1 was found in pretreated breast cancer patients as compared to controls. The n-3/n-6 ratio of breast cancer patients was decreased before treatment but it was 35% increased after treatment. In addition, plasma activity of D6 desaturase was increased in the breast cancer patients, while the activity of D5 desaturase was decreased. Increased levels of SFAs, monounsaturated fatty acids (MUFAs) and decreased polyunsaturated fatty acids (PUFAs) levels in breast cancer patients (pre and post treated) as compared to controls. Serum total cholesterol (TC) (224.4 mg/dL) and low density lipoprotein cholesterol (LDL-C) (142.9 mg/dL) were significantly increased in pretreated breast cancer patients but after the radiotherapy treatment, the TC (150.2 mg/dL) and LDL-C (89.8 mg/dL) were decreased. It seems that RT would have played a potential role in the treatment of BC. After RT the serum levels of PUFAs, TC, and LDL-C are improved. Our study reinforces the important role of RT in the management of BC. The level of PUFAs, TC, and LDL-C can be

  10. Selective reduction of AKR1C2 in prostate cancer and its role in DHT metabolism.

    Science.gov (United States)

    Ji, Qing; Chang, Lilly; VanDenBerg, David; Stanczyk, Frank Z; Stolz, Andrew

    2003-03-01

    As androgens play an essential role in prostate cancer, we sought to develop a real-time PCR to characterize mRNA expression profiles of human members of the Aldo-Keto Reductase (AKR) 1C gene family, as well as of 5 alpha-steroid reductase Type II (SRD5A2) in prostate cancer samples. Functional activity and regulation of AKR1C2, a 3 alpha-hydroxysteroid dehydrogenase (HSD) type III, was also assessed in prostate cancer cell lines. Gene specific PCR primers were established and relative gene expression of human AKR1C family members was determined in paired samples of cancerous and surrounding unaffected prostate tissue. AKR1C2 preferentially reduces DHT to the weak metabolite 5 alpha-androstane-3 alpha,17 beta-diol (3 alpha-diol) without conversion of 3 alpha-diol to DHT in the PC-3 cell line, and its expression was increased by DHT treatment in LNCaP cells. Selectively reduced expression of AKR1C2 mRNA, but not AKR1C1 (97% sequence identity), was found in approximately half of the pairs whereas AKR1C3 relative expression was not significantly altered. No aberrant expression of AKR1C4 expression or significant differences in SRD5A2 gene expression were found. AKR1C2 functions as a DHT reductase in prostate-derived cells lines and is regulated by DHT. Additional studies are needed to further define the significance of reduced AKR1C2 expression in prostate cancer and its potential role in modulating local availability of DHT. Copyright 2003 Wiley-Liss, Inc.

  11. The association between ATM IVS 22-77 T>C and cancer risk: a meta-analysis.

    Directory of Open Access Journals (Sweden)

    Lin Zhao

    Full Text Available BACKGROUND AND OBJECTIVES: It has become increasingly clear that ATM (ataxia-telangiectasia-mutated safeguards genome stability, which is a cornerstone of cellular homeostasis, and ATM IVS 22-77 T>C affects the normal activity of ATM proteins. However, the association between the ATM IVS 22-77 T>C genetic variant and cancer risk is controversial. Therefore, we conducted a systematic meta-analysis to estimate the overall cancer risk associated with the polymorphism and to quantify any potential between-study heterogeneity. METHODS: A total of nine studies including 4,470 cases and 4,862 controls were analyzed for ATM IVS 22-77 T>C association with cancer risk in this meta-analysis. Heterogeneity among articles and their publication bias were also tested. RESULTS: Our results showed that no association reached the level of statistical significance in the overall risk. Interestingly, in the stratified analyses, we observed an inverse relationship in lung and breast cancer. CONCLUSION: Further functional research on the ATM mechanism should be performed to explain the inconsistent results in different cancer types.

  12. Association of (C677T Gene Polymorphism with Breast Cancer in North India

    Directory of Open Access Journals (Sweden)

    Mohammad Waseem

    2016-01-01

    Full Text Available Background Breast cancer is one of the most common malignancies in women and is associated with a variety of risk factors. The functional single-nucleotide polymorphism (SNP C677T in the gene encoding 5,10-methylenetetrahydrofolate reductase (MTHFR may lead to decreased enzyme activity and affect the chemosensitivity of tumor cells. This study was designed to investigate the association of MTHFR gene polymorphism (SNP in the pathogenesis of breast cancer among the North Indian women population. Materials and Methods Genotyping was performed by polymerase chain reaction (PCR using genomic DNA, extracted from the peripheral blood of subjects with (275 cases or without (275 controls breast cancer. Restriction fragment length polymorphism was used to study C677T polymorphism in the study groups. Results The distribution of MTHFR (C677T genotype frequencies, ie, CC, TT, and CT, among the patients was 64.7%, 2.18%, and 33.09%, respectively. In the healthy control group, the CC, TT, and CT frequencies were 78.91%, 1.09%, and 20.1%, respectively. The frequencies of C and T alleles were 81.2% and 18.7%, respectively, in the patient subjects, while they were 88.9% and 11.09%, respectively, among the healthy control group. Frequencies of the CT genotype and the T allele were significantly different ( P = 0.007 and P = 0.005, respectively between the control and the case subjects. Conclusion This study shows an association of the CT genotype and the T allele of the MTHFR (C667T gene with increased genetic risk for breast cancer among Indian women.

  13. AXAIR89Q User's Manual

    International Nuclear Information System (INIS)

    Simpkins, A.A.

    1994-04-01

    AXAIR89Q is the primary dose assessment code used at the Savannah River Site to predict downwind doses following a hypothetical atmospheric release of relatively short duration. The primary purpose of the code is to perform calculations for safety-related documentation, and there is strict adherence in AXAIR89Q to the guidance in USNRC Regulatory Guide 1.145 (USNRC, 1983) entitled Atmospheric Dispersion Models for Potential Accident Consequence Assessments at Nuclear Power Plants. Doses are determined for the cloud shine, and inhalation pathways. Ingestion and ground shine are not considered. Future modifications are expected to include these features. This report discusses the information needed to execute the program and interpret the results

  14. A short synthetic peptide fragment of human C2ORF40 has therapeutic potential in breast cancer

    Energy Technology Data Exchange (ETDEWEB)

    Lin, Chaoyang [Shandong Univ., Jinan (China); Zhang, Pengju [Shandong Univ., Jinan (China); Jiang, Anli [Shandong Univ., Jinan (China); Mao, Jian-Hua [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States); Wei, Guangwei [Shandong Univ. School of Medicine, Jinan (China)

    2017-03-30

    C2ORF40 encodes a secreted protein which is cleaved to generate soluble peptides by proteolytic processing and this process is believed to be necessary for C2ORF40 to exert cell type specific biological activity. Here, we reported a short mimic peptide of human C2ORF40 acts potential therapeutic efficacy in human cancer cells in vitro and in vivo. We synthesized a short peptide of human C2ORF40, named C2ORF40 mimic peptide fragment and assessed its biological function on cancer cell growth, migration and tumorigenesis. Cell growth assay showed that C2ORF40 mimic peptide fragment significantly suppressed cell proliferation of breast and lung cancer cells. Moreover, C2ORF40 mimic peptide fragment significantly inhibited the migration and invasion of breast cancer cells. Furthermore, we showed that this peptide suppressed tumorigenesis in breast tumor xenograft model. Cell cycle assay indicated that the C2ORF40 mimic peptide fragment suppressed the growth of tumor cells through inducing mitotic phase arrest. In conclusion, our results firstly suggested that this short synthetic peptide of human C2ORF40 may be a candidate tumor therapeutic agent.

  15. Evaluation of macrocyclic hydroxyisophthalamide ligands as chelators for zirconium-89.

    Science.gov (United States)

    Bhatt, Nikunj B; Pandya, Darpan N; Xu, Jide; Tatum, David; Magda, Darren; Wadas, Thaddeus J

    2017-01-01

    The development of bifunctional chelators (BFCs) for zirconium-89 immuno-PET applications is an area of active research. Herein we report the synthesis and evaluation of octadentate hydroxyisophthalamide ligands (1 and 2) as zirconium-89 chelators. While both radiometal complexes could be prepared quantitatively and with excellent specific activity, preparation of 89Zr-1 required elevated temperature and an increased reaction time. 89Zr-1 was more stable than 89Zr-2 when challenged in vitro by excess DTPA or serum proteins and in vivo during acute biodistribution studies. Differences in radiometal complex stability arise from structural changes between the two ligand systems, and suggest further ligand optimization is necessary to enhance 89Zr chelation.

  16. Evaluation of macrocyclic hydroxyisophthalamide ligands as chelators for zirconium-89.

    Directory of Open Access Journals (Sweden)

    Nikunj B Bhatt

    Full Text Available The development of bifunctional chelators (BFCs for zirconium-89 immuno-PET applications is an area of active research. Herein we report the synthesis and evaluation of octadentate hydroxyisophthalamide ligands (1 and 2 as zirconium-89 chelators. While both radiometal complexes could be prepared quantitatively and with excellent specific activity, preparation of 89Zr-1 required elevated temperature and an increased reaction time. 89Zr-1 was more stable than 89Zr-2 when challenged in vitro by excess DTPA or serum proteins and in vivo during acute biodistribution studies. Differences in radiometal complex stability arise from structural changes between the two ligand systems, and suggest further ligand optimization is necessary to enhance 89Zr chelation.

  17. MUC1-C activates polycomb repressive complexes and downregulates tumor suppressor genes in human cancer cells.

    Science.gov (United States)

    Rajabi, Hasan; Hiraki, Masayuki; Kufe, Donald

    2018-04-01

    The PRC2 and PRC1 complexes are aberrantly expressed in human cancers and have been linked to decreases in patient survival. MUC1-C is an oncoprotein that is also overexpressed in diverse human cancers and is associated with a poor prognosis. Recent studies have supported a previously unreported function for MUC1-C in activating PRC2 and PRC1 in cancer cells. In the regulation of PRC2, MUC1-C (i) drives transcription of the EZH2 gene, (ii) binds directly to EZH2, and (iii) enhances occupancy of EZH2 on target gene promoters with an increase in H3K27 trimethylation. Regarding PRC1, which is recruited to PRC2 sites in the hierarchical model, MUC1-C induces BMI1 transcription, forms a complex with BMI1, and promotes H2A ubiquitylation. MUC1-C thereby contributes to the integration of PRC2 and PRC1-mediated repression of tumor suppressor genes, such as CDH1, CDKN2A, PTEN and BRCA1. Like PRC2 and PRC1, MUC1-C is associated with the epithelial-mesenchymal transition (EMT) program, cancer stem cell (CSC) state, and acquisition of anticancer drug resistance. In concert with these observations, targeting MUC1-C downregulates EZH2 and BMI1, inhibits EMT and the CSC state, and reverses drug resistance. These findings emphasize the significance of MUC1-C as a therapeutic target for inhibiting aberrant PRC function and reprogramming the epigenome in human cancers.

  18. Control Of DC 30V/15A Power Supply Using AT89C Micro controller By Look-Up Table Method For Magnetization System Application

    International Nuclear Information System (INIS)

    Abdillah, Arieko; Hermanto, Lingga; Manaf, Azwar

    2003-01-01

    Experiment of Control System Dc current based on micro controller Atm el AT89C52 has been done. Micro controller controls the transistors that will be activate. These transistors will allow the DC current passed trough to produce a homogeneous of magnetic field. This system produce DC current from 1,8 A to 12 A that produce the magnetic field measures from 23 mT to 325 mT. All manner of data using look-up table method. Micro controller and power supply circuit were isolated by optocoupler. This system can be used as first prototypes of control system of magnetic field for magnetize purpose

  19. Redox biology in normal cells and cancer: restoring function of the redox/Fyn/c-Cbl pathway in cancer cells offers new approaches to cancer treatment.

    Science.gov (United States)

    Noble, Mark; Mayer-Pröschel, Margot; Li, Zaibo; Dong, Tiefei; Cui, Wanchang; Pröschel, Christoph; Ambeskovic, Ibro; Dietrich, Joerg; Han, Ruolan; Yang, Yin Miranda; Folts, Christopher; Stripay, Jennifer; Chen, Hsing-Yu; Stevens, Brett M

    2015-02-01

    This review discusses a unique discovery path starting with novel findings on redox regulation of precursor cell and signaling pathway function and identification of a new mechanism by which relatively small changes in redox status can control entire signaling networks that regulate self-renewal, differentiation, and survival. The pathway central to this work, the redox/Fyn/c-Cbl (RFC) pathway, converts small increases in oxidative status to pan-activation of the c-Cbl ubiquitin ligase, which controls multiple receptors and other proteins of central importance in precursor cell and cancer cell function. Integration of work on the RFC pathway with attempts to understand how treatment with systemic chemotherapy causes neurological problems led to the discovery that glioblastomas (GBMs) and basal-like breast cancers (BLBCs) inhibit c-Cbl function through altered utilization of the cytoskeletal regulators Cool-1/βpix and Cdc42, respectively. Inhibition of these proteins to restore normal c-Cbl function suppresses cancer cell division, increases sensitivity to chemotherapy, disrupts tumor-initiating cell (TIC) activity in GBMs and BLBCs, controls multiple critical TIC regulators, and also allows targeting of non-TICs. Moreover, these manipulations do not increase chemosensitivity or suppress division of nontransformed cells. Restoration of normal c-Cbl function also allows more effective harnessing of estrogen receptor-α (ERα)-independent activities of tamoxifen to activate the RFC pathway and target ERα-negative cancer cells. Our work thus provides a discovery strategy that reveals mechanisms and therapeutic targets that cannot be deduced by standard genetics analyses, which fail to reveal the metabolic information, isoform shifts, protein activation, protein complexes, and protein degradation critical to our discoveries. Copyright © 2015. Published by Elsevier Inc.

  20. Mapping EORTC QLQ-C30 onto EQ-5D for the assessment of cancer patients

    Directory of Open Access Journals (Sweden)

    Kim Seon Ha

    2012-12-01

    Full Text Available Abstract Background The European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30 is the instrument most frequently used to measure quality of life in cancer patients, whereas the EQ-5D is widely used to measure and evaluate general health status. Although the EORTC QLQ-C30 has been mapped to EQ-5D utilities, those studies were limited to patients with a single type of cancer. The present study aimed to develop a mapping relationship between the EORTC QLQ-C30 and EQ-5D-based utility values at the individual level. Methods The model was derived using patients with different types of cancer who were receiving chemotherapy. The external validation set comprised outpatients with colon cancer. Ordinary least squares regression was used to estimate the EQ-5D index from the EORTC QLQ-C30 results. The predictability, goodness of fit, and signs of the estimated coefficients of the model were assessed. Predictive ability was determined by calculating the mean absolute error, the estimated proportions with absolute errors > 0.05 and > 0.1, and the root-mean-squared error (RMSE. Results A model that included global health, physical, role, emotional functions, and pain was optimal, with a mean absolute error of 0.069 and an RMSE of 0.095 (normalized RMSE, 8.1%. The explanatory power of this model was 51.6%. The mean absolute error was higher for modeled patients in poor health. Conclusions This mapping algorithm enabled the EORTC QLQ-C30 to be converted to the EQ-5D utility index to assess cancer patients in Korea.

  1. Cisplatin and ultra-violet-C synergistically down-regulate receptor tyrosine kinases in human colorectal cancer cells

    Directory of Open Access Journals (Sweden)

    Kawaguchi Junji

    2012-07-01

    Full Text Available Abstract Background Platinum-containing anti-cancer drugs such as cisplatin are widely used for patients with various types of cancers, however, resistance to cisplatin is observed in some cases. Whereas we have recently reported that high dose UV-C (200 J/m² induces colorectal cancer cell proliferation by desensitization of EGFR, which leads oncogenic signaling in these cells, in this study we investigated the combination effect of low dose cisplatin (10 μM and low dose UV-C (10 J/m² on cell growth and apoptosis in several human colorectal cancer cells, SW480, DLD-1, HT29 and HCT116. Results The combination inhibited cell cycle and colony formation, while either cisplatin or UV-C alone had little effect. The combination also induced apoptosis in these cells. In addition, the combination caused the downregulation of EGFR and HER2. Moreover, UV-C alone caused the transient internalization of the EGFR, but with time EGFR recycled back to the cell surface, while cisplatin did not affect its localization. Surprisingly, the combination caused persistent internalization of the EGFR, which results in the lasting downregulation of the EGFR. Conclusions The combination of low dose cisplatin and low dose UV-C synergistically exerted anti-cancer effect by down-regulating RTK, such as EGFR and HER2. These findings may provide a novel strategy for the treatment of patients with colorectal cancer.

  2. Activation of c-MET induces a stem-like phenotype in human prostate cancer.

    Directory of Open Access Journals (Sweden)

    Geert J L H van Leenders

    Full Text Available Prostate cancer consists of secretory cells and a population of immature cells. The function of immature cells and their mutual relation with secretory cells are still poorly understood. Immature cells either have a hierarchical relation to secretory cells (stem cell model or represent an inducible population emerging upon appropriate stimulation of differentiated cells. Hepatocyte Growth Factor (HGF receptor c-MET is specifically expressed in immature prostate cells. Our objective is to determine the role of immature cells in prostate cancer by analysis of the HGF/c-MET pathway.Gene-expression profiling of DU145 prostate cancer cells stimulated with HGF revealed induction of a molecular signature associated with stem cells, characterized by up-regulation of CD49b, CD49f, CD44 and SOX9, and down-regulation of CD24 ('stem-like signature'. We confirmed the acquisition of a stem-like phenotype by quantitative PCR, FACS analysis and Western blotting. Further, HGF led to activation of the stem cell related Notch pathway by up-regulation of its ligands Jagged-1 and Delta-like 4. Small molecules SU11274 and PHA665752 targeting c-MET activity were both able to block the molecular and biologic effects of HGF. Knock-down of c-MET by shRNA infection resulted in significant reduction and delay of orthotopic tumour-formation in male NMRI mice. Immunohistochemical analysis in prostatectomies revealed significant enrichment of c-MET positive cells at the invasive front, and demonstrated co-expression of c-MET with stem-like markers CD49b and CD49f.In conclusion, activation of c-MET in prostate cancer cells induced a stem-like phenotype, indicating a dynamic relation between differentiated and stem-like cells in this malignancy. Its mediation of efficient tumour-formation in vivo and predominant receptor expression at the invasive front implicate that c-MET regulates tumour infiltration in surrounding tissues putatively by acquisition of a stem-like phenotype.

  3. Cystatin C deficiency suppresses tumor growth in a breast cancer model through decreased proliferation of tumor cells.

    Science.gov (United States)

    Završnik, Janja; Butinar, Miha; Prebanda, Mojca Trstenjak; Krajnc, Aleksander; Vidmar, Robert; Fonović, Marko; Grubb, Anders; Turk, Vito; Turk, Boris; Vasiljeva, Olga

    2017-09-26

    Cysteine cathepsins are proteases that, in addition to their important physiological functions, have been associated with multiple pathologies, including cancer. Cystatin C (CstC) is a major endogenous inhibitor that regulates the extracellular activity of cysteine cathepsins. We investigated the role of cystatin C in mammary cancer using CstC knockout mice and a mouse model of breast cancer induced by expression of the polyoma middle T oncoprotein (PyMT) in the mammary epithelium. We showed that the ablation of CstC reduced the rate of mammary tumor growth. Notably, a decrease in the proliferation of CstC knockout PyMT tumor cells was demonstrated ex vivo and in vitro , indicating a role for this protease inhibitor in signaling pathways that control cell proliferation. An increase in phosphorylated p-38 was observed in CstC knockout tumors, suggesting a novel function for cystatin C in cancer development, independent of the TGF-β pathway. Moreover, proteomic analysis of the CstC wild-type and knockout PyMT primary cell secretomes revealed a decrease in the levels of 14-3-3 proteins in the secretome of knock-out cells, suggesting a novel link between cysteine cathepsins, cystatin C and 14-3-3 proteins in tumorigenesis, calling for further investigations.

  4. Value of {sup 11}C-choline PET and PET/CT in patients with suspected prostate cancer

    Energy Technology Data Exchange (ETDEWEB)

    Scher, Bernhard; Albinger, Wolfram; Tiling, Reinhold; Gildehaus, Franz-Josef; Dresel, Stefan [University of Munich, Department of Nuclear Medicine, Munich (Germany); Seitz, Michael [University of Munich, Department of Urology, Munich (Germany); Scherr, Michael; Becker, Hans-Christoph [University of Munich, Department of Radiology, Munich (Germany); Souvatzogluou, Michael; Wester, Hans-Juergen [Technical University of Munich, Department of Nuclear Medicine, Munich (Germany)

    2007-01-15

    The value and limitations of {sup 11}C-choline PET and PET/CT for the detection of prostate cancer remain controversial. The aim of this study was to investigate the diagnostic efficacy of {sup 11}C-choline PET and PET/CT in a large group of patients with suspected prostate cancer. Fifty-eight patients with clinical suspicion of prostate cancer underwent {sup 11}C-choline PET (25/58, Siemens ECAT Exact HR+) or PET/CT (33/58, Philips Gemini) scanning. On average, 500 MBq of {sup 11}C-choline was administered intravenously. Studies were interpreted by raters blinded to clinical information and other diagnostic procedures. Qualitative image analysis as well as semiquantitative SUV measurement was carried out. The reference standard was histopathological examination of resection specimens or biopsy. Prevalence of prostate cancer in this selected patient population was 63.8% (37/58). {sup 11}C-choline PET and PET/CT showed a sensitivity of 86.5% (32/37) and a specificity of 61.9% (13/21) in the detection of the primary malignancy. With regard to metastatic spread, PET showed a per-patient sensitivity of 81.8% (9/11) and produced no false positive findings. Based on our findings, differentiation between benign prostatic changes, such as benign prostatic hyperplasia or prostatitis, and prostate cancer is feasible in the majority of cases when image interpretation is primarily based on qualitative characteristics. SUV{sub max} may serve as guidance. False positive findings may occur due to an overlap of {sup 11}C-choline uptake between benign and malignant processes. By providing functional information regarding both the primary malignancy and its metastases, {sup 11}C-choline PET may prove to be a useful method for staging prostate cancer. (orig.)

  5. Rictor regulates FBXW7-dependent c-Myc and cyclin E degradation in colorectal cancer cells

    Energy Technology Data Exchange (ETDEWEB)

    Guo, Zheng [Markey Cancer Center, The University of Kentucky, 800 Rose Street, Lexington, KY 40536 (United States); Guangdong Provincial Key Laboratory of Gastroenterology, Department of Gastroenterology, Nanfang Hospital, Southern Medical University, 1838 Guangzhou Dadao Bei, Guangzhou 510515 (China); Zhou, Yuning [Markey Cancer Center, The University of Kentucky, 800 Rose Street, Lexington, KY 40536 (United States); Evers, B. Mark [Markey Cancer Center, The University of Kentucky, 800 Rose Street, Lexington, KY 40536 (United States); Department of Surgery, The University of Kentucky, 800 Rose Street, Lexington, KY 40536 (United States); Wang, Qingding, E-mail: qingding.wang@uky.edu [Markey Cancer Center, The University of Kentucky, 800 Rose Street, Lexington, KY 40536 (United States); Department of Surgery, The University of Kentucky, 800 Rose Street, Lexington, KY 40536 (United States)

    2012-02-10

    Highlights: Black-Right-Pointing-Pointer Rictor associates with FBXW7 to form an E3 complex. Black-Right-Pointing-Pointer Knockdown of rictor decreases ubiquitination of c-Myc and cylin E. Black-Right-Pointing-Pointer Knockdown of rictor increases protein levels of c-Myc and cylin E. Black-Right-Pointing-Pointer Overexpression of rictor induces the degradation of c-Myc and cyclin E proteins. Black-Right-Pointing-Pointer Rictor regulation of c-Myc and cyclin E requires FBXW7. -- Abstract: Rictor (Rapamycin-insensitive companion of mTOR) forms a complex with mTOR and phosphorylates and activates Akt. Activation of Akt induces expression of c-Myc and cyclin E, which are overexpressed in colorectal cancer and play an important role in colorectal cancer cell proliferation. Here, we show that rictor associates with FBXW7 to form an E3 complex participating in the regulation of c-Myc and cyclin E degradation. The Rictor-FBXW7 complex is biochemically distinct from the previously reported mTORC2 and can be immunoprecipitated independently of mTORC2. Moreover, knocking down of rictor in serum-deprived colorectal cancer cells results in the decreased ubiquitination and increased protein levels of c-Myc and cyclin E while overexpression of rictor induces the degradation of c-Myc and cyclin E proteins. Genetic knockout of FBXW7 blunts the effects of rictor, suggesting that rictor regulation of c-Myc and cyclin E requires FBXW7. Our findings identify rictor as an important component of FBXW7 E3 ligase complex participating in the regulation of c-Myc and cyclin E protein ubiquitination and degradation. Importantly, our results suggest that elevated growth factor signaling may contribute to decrease rictor/FBXW7-mediated ubiquitination of c-Myc and cyclin E, thus leading to accumulation of cyclin E and c-Myc in colorectal cancer cells.

  6. Rictor regulates FBXW7-dependent c-Myc and cyclin E degradation in colorectal cancer cells

    International Nuclear Information System (INIS)

    Guo, Zheng; Zhou, Yuning; Evers, B. Mark; Wang, Qingding

    2012-01-01

    Highlights: ► Rictor associates with FBXW7 to form an E3 complex. ► Knockdown of rictor decreases ubiquitination of c-Myc and cylin E. ► Knockdown of rictor increases protein levels of c-Myc and cylin E. ► Overexpression of rictor induces the degradation of c-Myc and cyclin E proteins. ► Rictor regulation of c-Myc and cyclin E requires FBXW7. -- Abstract: Rictor (Rapamycin-insensitive companion of mTOR) forms a complex with mTOR and phosphorylates and activates Akt. Activation of Akt induces expression of c-Myc and cyclin E, which are overexpressed in colorectal cancer and play an important role in colorectal cancer cell proliferation. Here, we show that rictor associates with FBXW7 to form an E3 complex participating in the regulation of c-Myc and cyclin E degradation. The Rictor–FBXW7 complex is biochemically distinct from the previously reported mTORC2 and can be immunoprecipitated independently of mTORC2. Moreover, knocking down of rictor in serum-deprived colorectal cancer cells results in the decreased ubiquitination and increased protein levels of c-Myc and cyclin E while overexpression of rictor induces the degradation of c-Myc and cyclin E proteins. Genetic knockout of FBXW7 blunts the effects of rictor, suggesting that rictor regulation of c-Myc and cyclin E requires FBXW7. Our findings identify rictor as an important component of FBXW7 E3 ligase complex participating in the regulation of c-Myc and cyclin E protein ubiquitination and degradation. Importantly, our results suggest that elevated growth factor signaling may contribute to decrease rictor/FBXW7-mediated ubiquitination of c-Myc and cyclin E, thus leading to accumulation of cyclin E and c-Myc in colorectal cancer cells.

  7. Quantitative assessment of Zirconium-89 labeled cetuximab using PET/CT imaging in patients with advanced head and neck cancer: a theragnostic approach.

    Science.gov (United States)

    Even, Aniek J G; Hamming-Vrieze, Olga; van Elmpt, Wouter; Winnepenninckx, Véronique J L; Heukelom, Jolien; Tesselaar, Margot E T; Vogel, Wouter V; Hoeben, Ann; Zegers, Catharina M L; Vugts, Daniëlle J; van Dongen, Guus A M S; Bartelink, Harry; Mottaghy, Felix M; Hoebers, Frank; Lambin, Philippe

    2017-01-17

    Biomarkers predicting treatment response to the monoclonal antibody cetuximab in locally advanced head and neck squamous cell carcinomas (LAHNSCC) are lacking. We hypothesize that tumor accessibility is an important factor in treatment success of the EGFR targeting drug. We quantified uptake of cetuximab labeled with Zirconium-89 (89Zr) using PET/CT imaging.Seventeen patients with stage III-IV LAHNSCC received a loading dose unlabeled cetuximab, followed by 10 mg 54.5±9.6 MBq 89Zr-cetuximab. PET/CT images were acquired either 3 and 6 or 4 and 7 days post-injection. 89Zr-cetuximab uptake was quantified using standardized uptake value (SUV) and tumor-to-background ratio (TBR), and correlated to EGFR immunohistochemistry. TBR was compared between scan days to determine optimal timing.Uptake of 89Zr-cetuximab varied between patients (day 6-7: SUVpeak range 2.5-6.2). TBR increased significantly (49±28%, p < 0.01) between first (1.1±0.3) and second scan (1.7±0.6). Between groups with a low and high EGFR expression a significant difference in SUVmean (2.1 versus 3.0) and SUVpeak (3.2 versus 4.7) was found, however, not in TBR. Data is available at www.cancerdata.org (DOI: 10.17195/candat.2016.11.1).In conclusion, 89Zr-cetuximab PET imaging shows large inter-patient variety in LAHNSCC and provides additional information over FDG-PET and EGFR expression. Validation of the predictive value is recommended with scans acquired 6-7 days post-injection.

  8. Intake of vitamins A, C, and E from diet and supplements and breast cancer in postmenopausal women

    DEFF Research Database (Denmark)

    Nissen, S. B.; Tjonneland, A.; Stripp, C.

    2003-01-01

    Objective: The influence of the vitamins A, C, and E on breast cancer development has not been clarified. An effect of a vitamin per se implicates similar patterns for the effects of the vitamin from dietary and supplemental sources. We examined how the breast cancer incidence rate among...... A or E for postmenopausal women. For vitamin C we found an increase in breast cancer rate with increasing intake....... postmenopausal women was related to intake of vitamins A, C, and E from diet and supplements. Methods: Data was sampled as case - control nested within the Danish 'Diet, Cancer and Health' cohort. Data on vitamin intakes were collected at entry into the cohort by means of self-administered questionnaires. Women...

  9. Dicty_cDB: Contig-U12196-1 [Dicty_cDB

    Lifescience Database Archive (English)

    Full Text Available RecName: Full=Mitochondrial import inner membrane trans... 103 8e-21 BC122182_1( BC122182 |pid:none) Danio rerio CTD (carboxy-term...d:none) Leishmania braziliensis chromoso... 53 2e-05 (Q8SV03) RecName: Full=RNA polymerase II subunit A C-term...ecName: Full=RNA polymerase II subunit A C-terminal do... 39 0.18 BC063447_1( BC063447 |pid:none) Homo sapiens CTD (carboxy-term...clone BO... 44 8.9 1 ( ER303350 ) 1092343723909 Global-Ocean-Sampling_GS-34-01-01-1... 44 8.9 1 ( EJ487331 )... 1095403512301 Global-Ocean-Sampling_GS-28-01-01-1... 44 8.9 1 ( EJ415060 ) 10930

  10. Involvement of miR-30c in resistance to doxorubicin by regulating YWHAZ in breast cancer cells

    Energy Technology Data Exchange (ETDEWEB)

    Fang, Y. [Department of Central Laboratory, The First Affiliated People’s Hospital, Jiangsu University, Zhenjiang, Jiangsu (China); Shen, H. [Department of Oncology, The First Affiliated People’s Hospital, Jiangsu University, Zhenjiang, Jiangsu (China); Cao, Y. [Department of Central Laboratory, The First Affiliated People’s Hospital, Jiangsu University, Zhenjiang, Jiangsu (China); Li, H. [Department of Central Laboratory, The Fourth Affiliated People’s Hospital, Jiangsu University, Zhenjiang, Jiangsu (China); Qin, R. [Department of Oncology, The First Affiliated People’s Hospital, Jiangsu University, Zhenjiang, Jiangsu (China); Chen, Q. [Department of Central Laboratory, The First Affiliated People’s Hospital, Jiangsu University, Zhenjiang, Jiangsu (China); Long, L. [Department of Oncology, The First Affiliated People’s Hospital, Jiangsu University, Zhenjiang, Jiangsu (China); Zhu, X.L. [Department of Central Laboratory, The Fourth Affiliated People’s Hospital, Jiangsu University, Zhenjiang, Jiangsu (China); Xie, C.J. [Department of Central Laboratory, The First Affiliated People’s Hospital, Jiangsu University, Zhenjiang, Jiangsu (China); Xu, W.L. [Department of Central Laboratory, The Fourth Affiliated People’s Hospital, Jiangsu University, Zhenjiang, Jiangsu (China)

    2014-01-10

    MicroRNAs (miRNAs) are small RNA molecules that modulate gene expression implicated in cancer, which play crucial roles in diverse biological processes, such as development, differentiation, apoptosis, and proliferation. The aim of this study was to investigate whether miR-30c mediated the resistance of breast cancer cells to the chemotherapeutic agent doxorubicin (ADR) by targeting tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein zeta (YWHAZ). miR-30c was downregulated in the doxorubicin-resistant human breast cancer cell lines MCF-7/ADR and MDA-MB-231/ADR compared with their parental MCF-7 and MDA-MB-231 cell lines, respectively. Furthermore, we observed that transfection of an miR-30c mimic significantly suppressed the ability of MCF-7/ADR to resist doxorubicin. Moreover, the anti-apoptotic gene YWHAZ was confirmed as a target of miR-30c by luciferase reporter assay, and further studies indicated that the mechanism for miR-30c on the sensitivity of breast cancer cells involved YWHAZ and its downstream p38 mitogen-activated protein kinase (p38MAPK) pathway. Together, our findings provided evidence that miR-30c was one of the important miRNAs in doxorubicin resistance by regulating YWHAZ in the breast cancer cell line MCF-7/ADR.

  11. Diagnostic value of computed tomography in the colon cancer; In terms of the staging system

    International Nuclear Information System (INIS)

    Lee, Joo Mi; Moon, Jang Ho; Lee, Dong Joong; Choi, Chul Soon; Kang, Ik Won; Chung, Soo Young; Bae, Sang Hoon; Yoon, Jong Sub

    1989-01-01

    The CT findings of thirty-three patients with proven colon cancer were analysed. The results were as follows; 1. The accuracy for detecting pericolic fat invasion on CT was 81%. 2. The accuracy for detecting lymph node involvement on CT was 67%. 3. The overall accuracy for staging of colon cancer on CT was 64%(67% for stage A, 30% for stage B, 60% for stage C, 100% for stage D). 4. The overall detection rate of mass on CT was 80%(89% for rectum, 100% for rectosigmoid colon and sigmoid colon, 30% for ascending and transverse colon). 5. The CT is useful, noninvasive technique for assessing extension and staging of colon cancer

  12. Ovary cancer incidence and mortality in China, 2011.

    Science.gov (United States)

    Wei, Kuangrong; Li, Yuanming; Zheng, Rongshou; Zhang, Siwei; Liang, Zhiheng; Cen, Huishan; Chen, Wanqing

    2015-02-01

    To evaluate and analyze ovary cancer incidence and mortality in China in 2011 using ovary cancer data from population-based cancer registration in China, and to provide scientific information for its control and prevention. Invasive cases of ovary cancer were extracted and analyzed from the overall Chinese cancer database in 2011, which were based on data from 177 population-based cancer registries distributing in 28 provinces. The crude, standardized, and truncated incidences and mortalities et al. were calculated and new and deaths cases from ovary cancer throughout China and in different regions in 2011 were estimated using Chinese practical population. The estimates of new ovary cancer cases and deaths were 45,223 and 18,430, respectively, in China in 2011. The crude incidence rate, age-standardized rate by Chinese standard population (ASR-C) and age-standardized rate by world standard population (ASR-W) incidence were 6.89/100,000, 5.35/100,000 and 5.08/100,000, respectively; the crude, ASR-C and ASR-W mortalities were 2.81/100,000, 2.01/100,000 and 1.99/100,000, respectively. The incidence and mortality in urban areas were higher than those in rural areas. The age-specific incidence and mortality increased rapidly from age 35-39 and peaked at age 60-64 or 75-79 years. After age 45 or 55, the age-specific incidence and death rates in urban were much higher than those in rural areas. Compared with GLOBOCAN 2012 data, the ovary cancer incidence in China in 2011 was at middle level, but its mortality was at low level worldwide.

  13. The Dysregulation of Polyamine Metabolism in Colorectal Cancer Is Associated with Overexpression of c-Myc and C/EBPβ rather than Enterotoxigenic Bacteroides fragilis Infection

    Directory of Open Access Journals (Sweden)

    Anastasiya V. Snezhkina

    2016-01-01

    Full Text Available Colorectal cancer is one of the most common cancers in the world. It is well known that the chronic inflammation can promote the progression of colorectal cancer (CRC. Recently, a number of studies revealed a potential association between colorectal inflammation, cancer progression, and infection caused by enterotoxigenic Bacteroides fragilis (ETBF. Bacterial enterotoxin activates spermine oxidase (SMO, which produces spermidine and H2O2 as byproducts of polyamine catabolism, which, in turn, enhances inflammation and tissue injury. Using qPCR analysis, we estimated the expression of SMOX gene and ETBF colonization in CRC patients. We found no statistically significant associations between them. Then we selected genes involved in polyamine metabolism, metabolic reprogramming, and inflammation regulation and estimated their expression in CRC. We observed overexpression of SMOX, ODC1, SRM, SMS, MTAP, c-Myc, C/EBPβ (CREBP, and other genes. We found that two mediators of metabolic reprogramming, inflammation, and cell proliferation c-Myc and C/EBPβ may serve as regulators of polyamine metabolism genes (SMOX, AZIN1, MTAP, SRM, ODC1, AMD1, and AGMAT as they are overexpressed in tumors, have binding site according to ENCODE ChIP-Seq data, and demonstrate strong coexpression with their targets. Thus, increased polyamine metabolism in CRC could be driven by c-Myc and C/EBPβ rather than ETBF infection.

  14. Glucose metabolism determines resistance of cancer cells to bioenergetic crisis after cytochrome-c release.

    LENUS (Irish Health Repository)

    Huber, Heinrich J

    2011-03-01

    Many anticancer drugs activate caspases via the mitochondrial apoptosis pathway. Activation of this pathway triggers a concomitant bioenergetic crisis caused by the release of cytochrome-c (cyt-c). Cancer cells are able to evade these processes by altering metabolic and caspase activation pathways. In this study, we provide the first integrated system study of mitochondrial bioenergetics and apoptosis signalling and examine the role of mitochondrial cyt-c release in these events. In accordance with single-cell experiments, our model showed that loss of cyt-c decreased mitochondrial respiration by 95% and depolarised mitochondrial membrane potential ΔΨ(m) from -142 to -88 mV, with active caspase-3 potentiating this decrease. ATP synthase was reversed under such conditions, consuming ATP and stabilising ΔΨ(m). However, the direction and level of ATP synthase activity showed significant heterogeneity in individual cancer cells, which the model explained by variations in (i) accessible cyt-c after release and (ii) the cell\\'s glycolytic capacity. Our results provide a quantitative and mechanistic explanation for the protective role of enhanced glucose utilisation for cancer cells to avert the otherwise lethal bioenergetic crisis associated with apoptosis initiation.

  15. Methylenetetrahydrofolate reductase C677T polymorphism in patients with lung cancer in a Korean population

    Directory of Open Access Journals (Sweden)

    Yun Woo-Jun

    2011-02-01

    Full Text Available Abstract Background This study was designed to investigate an association between methylenetetrahydrofolate reductase (MTHFR C677T polymorphism and the risk of lung cancer in a Korean population. Methods We conducted a large-scale, case-control study involving 3938 patients with newly diagnosed lung cancer and 1700 healthy controls. Genotyping was performed with peripheral blood DNA for MTHFR C677T polymorphisms. Statistical significance was estimated by logistic regression analysis. Results The MTHFR C677T frequencies of CC, CT, and TT genotypes were 34.5%, 48.5%, and 17% among lung cancer patients, and 31.8%, 50.7%, and 17.5% in the controls, respectively. The MTHFR 677CT and TT genotype showed a weak protection against lung cancer compared with the homozygous CC genotype, although the results did not reach statistical significance. The age- and gender-adjusted odds ratio (OR of overall lung cancer was 0.90 (95% confidence interval (CI, 0.77-1.04 for MTHFR 677 CT and 0.88 (95% CI, 0.71-1.07 for MTHFR 677TT. However, after stratification analysis by histological type, the MTHFR 677CT genotype showed a significantly decreased risk for squamous cell carcinoma (age- and gender-adjusted OR, 0.78; 95% CI, 0.64-0.96. The combination of 677 TT homozygous with 677 CT heterozygous also appeared to have a protection effect on the risk of squamous cell carcinoma. We observed no significant interaction between the MTHFR C677T polymorphism and age and gender or smoking habit. Conclusions This is the first reported study focusing on the association between MTHFR C677T polymorphisms and the risk of lung cancer in a Korean population. The T allele was found to provide a weak protective association with lung squamous cell carcinoma.

  16. 49 CFR 8.9 - Information Security Review Committee.

    Science.gov (United States)

    2010-10-01

    ... 49 Transportation 1 2010-10-01 2010-10-01 false Information Security Review Committee. 8.9 Section.../DECLASSIFICATION/ACCESS Classification/Declassification of Information § 8.9 Information Security Review Committee. (a) There is hereby established a Department of Transportation Information Security Review Committee...

  17. C282Y polymorphism in the HFE gene is associated with risk of breast cancer.

    Science.gov (United States)

    Liu, Xiaoyan; Lv, Chunlei; Luan, Xiaorong; Lv, Ming

    2013-10-01

    The C282Y and H63D polymorphisms in the HFE gene have been implicated in susceptibility of breast cancer, but a number of studies have reported inconclusive results. The aim of this study is to investigate the association between the C282Y and H63D polymorphisms in the HFE gene and breast cancer risk by meta-analysis. We searched PubMed and Embase databases, covering all related studies until March 2, 2013. Statistical analysis was performed using STATA 10.0. A total of 7 studies including 1,720 cases and 18,296 controls for HFE C282Y polymorphism and 5 studies including 942 cases and 1,571 controls for HFE H63D polymorphism were included in the meta-analysis. The results showed that HFE C282Y polymorphism was significantly associated with increased risk of breast cancer under homozygotes vs. wild-type model (OR = 2.06, 95%CI = 1.19-3.58) and recessive model (OR = 1.98, 95%CI = 1.14-3.44) but not under heterozygotes vs. wild-type model (OR = 0.97, 95%CI = 0.70-1.35), dominant model (OR = 1.00, 95%CI = 0.72-1.40) and multiplicative model (OR = 1.04, 95%CI = 0.76-1.42). However, we did not find any association between HFE H63D polymorphism and breast cancer risk under all genetic models. This current meta-analysis suggested that C282Y polymorphism rather than H63D might be associated with increased risk of breast cancer.

  18. Elevated IGFIR expression regulating VEGF and VEGF-C predicts lymph node metastasis in human colorectal cancer

    International Nuclear Information System (INIS)

    Zhang, Chunhui; Hao, Li; Wang, Liang; Xiao, Yichuan; Ge, Hailiang; Zhu, Zhenya; Luo, Yunbao; Zhang, Yi; Zhang, Yanyun

    2010-01-01

    Insulin-like growth factor-I receptor (IGFIR) has been shown to regulate the tumor development. The objective of the current study is to determine the association of IGFIR with lymph node metastasis and to explore the related mechanism in human colorectal cancer in clinic. In a random series of 98 colorectal cancer patients, the expressions of IGFIR, vascular endothelial growth factor (VEGF) and VEGF-C were investigated by immunohistochemistry, and the association of these expressions with lymph node metastasis was statistically analyzed. The expressions of VEGF and VEGF-C in colorectal cancer cells stimulated with IGF-I were also examined by real-time quantitative reverse transcription-polymerase chain reaction and enzyme-linked immunosorbent assay. Higher rates of IGFIR (46%), VEGF (53%), and VEGF-C (46%) expression were found in colorectal cancer tissues than in normal and colorectal adenoma tissues. These expressions were significantly associated with clinicopathologic factors and lymph node status. We also found the concomitant high expressions of IGFIR/VEGF (P < 0.001) and IGFIR/VEGF-C (P = 0.001) had a stronger correlation with lymph node metastasis than did each alone or both low expressions. In addition, IGF-I could effectively induce the VEGF and VEGF-C mRNA expression and protein secretion in colorectal cancer cells expressing IGFIR molecules. Moreover, Patients who had strong staining for IGFIR, VEGF and VEGF-C showed significantly less favorable survival rates compared with patients who had low staining for these molecules (P < 0.001). The survival rates of patients who were both high expression of IGFIR/VEGF and IGFIR/VEGF-C also were significantly lower compared with patients who were negative or one of high expression of these molecules (P < 0.001). Together the findings indicated for the first time that simultaneous examination of the expressions of IGFIR, VEGF and VEGF-C will benefit the diagnosis of lymph node metastasis in order to assay the

  19. Determination of Sr-89/90

    International Nuclear Information System (INIS)

    Smodis, B.; Planinsek, Z.; Stegnar, P.

    1995-01-01

    Sample preparation and radiochemical analysis for the determination of Strontium 89 and Strontium 90 in various food and environmental samples including sediments, fruit and vegetables, milk, meat and fish is elaborated in this paper

  20. Standardized methods for the production of high specific-activity zirconium-89

    Science.gov (United States)

    Holland, Jason P.; Sheh, Yiauchung; Lewis, Jason S.

    2009-01-01

    Zirconium-89 is an attractive metallo-radionuclide for use in immunoPET due to the favorable decay characteristics. Standardized methods for the routine production and isolation of high purity and high specific-activity 89Zr using a small cyclotron are reported. Optimized cyclotron conditions reveal high average yields of 1.52 ± 0.11 mCi/μA·h at a proton beam energy of 15 MeV and current of 15 μA using a solid, commercially available 89Y-foil target (0.1 mm, 100% natural abundance). 89Zr was isolated in high radionuclidic and radiochemical purity (>99.99%) as [89Zr]Zr-oxalate by using a solid-phase hydroxamate resin with >99.5% recovery of the radioactivity. The effective specific-activity of 89Zr was found to be in the range 5.28 – 13.43 mCi/μg (470 – 1195 Ci/mmol) of zirconium. New methods for the facile production of [89Zr]Zr-chloride are reported. Radiolabeling studies using the trihydroxamate ligand desferrioxamine B (DFO) gave 100% radiochemical yields in 7 days. Small-animal PET imaging studies have demonstrated that free 89Zr(IV) ions administered as [89Zr]Zr-chloride accumulate in the liver whilst [89Zr]Zr-DFO is excreted rapidly via the kidneys within <20 min. These results have important implication for the analysis of immunoPET imaging of 89Zr-labeled monoclonal antibodies. The detailed methods described can be easily translated to other radiochemistry facilities and will facilitate the use of 89Zr in both basic science and clinical investigations. PMID:19720285

  1. Novel derivative of aminobenzenesulfonamide (3c) induces apoptosis in colorectal cancer cells through ROS generation and inhibits cell migration.

    Science.gov (United States)

    Al-Khayal, Khayal; Alafeefy, Ahmed; Vaali-Mohammed, Mansoor-Ali; Mahmood, Amer; Zubaidi, Ahmed; Al-Obeed, Omar; Khan, Zahid; Abdulla, Maha; Ahmad, Rehan

    2017-01-03

    Colorectal cancer (CRC) is the 3 rd most common type of cancer worldwide. New anti-cancer agents are needed for treating late stage colorectal cancer as most of the deaths occur due to cancer metastasis. A recently developed compound, 3c has shown to have potent antitumor effect; however the mechanism underlying the antitumor effect remains unknown. 3c-induced inhibition of proliferation was measured in the absence and presence NAC using MTT in HT-29 and SW620 cells and xCELLigence RTCA DP instrument. 3c-induced apoptotic studies were performed using flow cytometry. 3c-induced redox alterations were measured by ROS production using fluorescence plate reader and flow cytometry and mitochondrial membrane potential by flow cytometry; NADPH and GSH levels were determined by colorimetric assays. Bcl2 family protein expression and cytochrome c release and PARP activation was done by western blotting. Caspase activation was measured by ELISA. Cell migration assay was done using the real time xCELLigence RTCA DP system in SW620 cells and wound healing assay in HT-29. Many anticancer therapeutics exert their effects by inducing reactive oxygen species (ROS). In this study, we demonstrate that 3c-induced inhibition of cell proliferation is reversed by the antioxidant, N-acetylcysteine, suggesting that 3c acts via increased production of ROS in HT-29 cells. This was confirmed by the direct measurement of ROS in 3c-treated colorectal cancer cells. Additionally, treatment with 3c resulted in decreased NADPH and glutathione levels in HT-29 cells. Further, investigation of the apoptotic pathway showed increased release of cytochrome c resulting in the activation of caspase-9, which in turn activated caspase-3 and -6. 3c also (i) increased p53 and Bax expression, (ii) decreased Bcl2 and BclxL expression and (iii) induced PARP cleavage in human colorectal cancer cells. Confirming our observations, NAC significantly inhibited induction of apoptosis, ROS production, cytochrome c

  2. An update on minding the gap in cancer.

    Science.gov (United States)

    Mesnil, Marc; Aasen, Trond; Boucher, Jonathan; Chépied, Amandine; Cronier, Laurent; Defamie, Norah; Kameritsch, Petra; Laird, Dale W; Lampe, Paul D; Lathia, Justin D; Leithe, Edward; Mehta, Parmender P; Monvoisin, Arnaud; Pogoda, Kristin; Sin, Wun-Chey; Tabernero, Arantxa; Yamasaki, Hiroshi; Yeh, Elizabeth S; Dagli, Maria Lucia Zaidan; Naus, Christian C

    2018-01-01

    This article is a report of the "International Colloquium on Gap junctions: 50Years of Impact on Cancer" that was held 8-9 September 2016, at the Amphitheater "Pôle Biologie Santé" of the University of Poitiers (Poitiers, France). The colloquium was organized by M Mesnil (Université de Poitiers, Poitiers, France) and C Naus (University of British Columbia, Vancouver, Canada) to celebrate the 50th anniversary of the seminal work published in 1966 by Loewenstein and Kanno [Intercellular communication and the control of tissue growth: lack of communication between cancer cells, Nature, 116 (1966) 1248-1249] which initiated studies on the involvement of gap junctions in carcinogenesis. During the colloquium, 15 participants presented reviews or research updates in the field which are summarized below. Copyright © 2017 Elsevier B.V. All rights reserved.

  3. cDNA sequencing improves the detection of P53 missense mutations in colorectal cancer

    International Nuclear Information System (INIS)

    Szybka, Malgorzata; Kordek, Radzislaw; Zakrzewska, Magdalena; Rieske, Piotr; Pasz-Walczak, Grazyna; Kulczycka-Wojdala, Dominika; Zawlik, Izabela; Stawski, Robert; Jesionek-Kupnicka, Dorota; Liberski, Pawel P

    2009-01-01

    Recently published data showed discrepancies beteween P53 cDNA and DNA sequencing in glioblastomas. We hypothesised that similar discrepancies may be observed in other human cancers. To this end, we analyzed 23 colorectal cancers for P53 mutations and gene expression using both DNA and cDNA sequencing, real-time PCR and immunohistochemistry. We found P53 gene mutations in 16 cases (15 missense and 1 nonsense). Two of the 15 cases with missense mutations showed alterations based only on cDNA, and not DNA sequencing. Moreover, in 6 of the 15 cases with a cDNA mutation those mutations were difficult to detect in the DNA sequencing, so the results of DNA analysis alone could be misinterpreted if the cDNA sequencing results had not also been available. In all those 15 cases, we observed a higher ratio of the mutated to the wild type template by cDNA analysis, but not by the DNA analysis. Interestingly, a similar overexpression of P53 mRNA was present in samples with and without P53 mutations. In terms of colorectal cancer, those discrepancies might be explained under three conditions: 1, overexpression of mutated P53 mRNA in cancer cells as compared with normal cells; 2, a higher content of cells without P53 mutation (normal cells and cells showing K-RAS and/or APC but not P53 mutation) in samples presenting P53 mutation; 3, heterozygous or hemizygous mutations of P53 gene. Additionally, for heterozygous mutations unknown mechanism(s) causing selective overproduction of mutated allele should also be considered. Our data offer new clues for studying discrepancy in P53 cDNA and DNA sequencing analysis

  4. Chemokine (C-X-C) ligand 1 (CXCL1) protein expression is increased in aggressive bladder cancers

    International Nuclear Information System (INIS)

    Miyake, Makito; Lawton, Adrienne; Goodison, Steve; Urquidi, Virginia; Gomes-Giacoia, Evan; Zhang, Ge; Ross, Shanti; Kim, Jeongsoon; Rosser, Charles J

    2013-01-01

    Chemokines, including chemokine (C-X-C motif) ligand 1 (CXCL1), may regulate tumor epithelial-stromal interactions that facilitate tumor growth and invasion. Studies have linked CXCL1 expression to gastric, colon and skin cancers, but limited studies to date have described CXCL1 protein expression in human bladder cancer (BCa). CXCL1 protein expression was examined in 152 bladder tissue specimens (142 BCa) by immunohistochemical staining. The expression of CXCL1 was scored by assigning a combined score based on the proportion of cells staining and intensity of staining. CXCL1 expression patterns were correlated with clinicopathological features and follow-up data. CXCL1 protein expression was present in cancerous tissues, but was entirely absent in benign tissue. CXCL1 combined immunostaining score was significantly higher in high-grade tumors relative to low-grade tumors (p = 0.012). Similarly, CXCL1 combined immunostaining score was higher in high stage tumors (T2-T4) than in low stage tumors (Ta-T1) (p < 0.0001). An increase in the combined immunostaining score of CXCL1 was also associated with reduced disease-specific survival. To date, this is the largest study describing increased CXCL1 protein expression in more aggressive phenotypes in human BCa. Further studies are warranted to define the role CXCL1 plays in bladder carcinogenesis and progression

  5. Clinical stage T1c prostate cancer: evaluation with endorectal MR imaging and MR spectroscopic imaging.

    Science.gov (United States)

    Zhang, Jingbo; Hricak, Hedvig; Shukla-Dave, Amita; Akin, Oguz; Ishill, Nicole M; Carlino, Lauren J; Reuter, Victor E; Eastham, James A

    2009-11-01

    To assess the diagnostic accuracy of endorectal magnetic resonance (MR) imaging and MR spectroscopic imaging for prediction of the pathologic stage of prostate cancer and the presence of clinically nonimportant disease in patients with clinical stage T1c prostate cancer. The institutional review board approved-and waived the informed patient consent requirement for-this HIPAA-compliant study involving 158 patients (median age, 58 years; age range, 40-76 years) who had clinical stage T1c prostate cancer, had not been treated preoperatively, and underwent combined 1.5-T endorectal MR imaging-MR spectroscopic imaging between January 2003 and March 2004 before undergoing radical prostatectomy. On the MR images and combined endorectal MR-MR spectroscopic images, two radiologists retrospectively and independently rated the likelihood of cancer in 12 prostate regions and the likelihoods of extracapsular extension (ECE), seminal vesicle invasion (SVI), and adjacent organ invasion by using a five-point scale, and they determined the probability of clinically nonimportant prostate cancer by using a four-point scale. Whole-mount step-section pathology maps were used for imaging-pathologic analysis correlation. Receiver operating characteristic curves were constructed and areas under the curves (AUCs) were estimated nonparametrically for assessment of reader accuracy. At surgical-pathologic analysis, one (0.6%) patient had no cancer; 124 (78%) patients, organ-confined (stage pT2) disease; 29 (18%) patients, ECE (stage pT3a); two (1%) patients, SVI (stage pT3b); and two (1%) patients, bladder neck invasion (stage pT4). Forty-six (29%) patients had a total tumor volume of less than 0.5 cm(3). With combined MR imaging-MR spectroscopic imaging, the two readers achieved 80% accuracy in disease staging and AUCs of 0.62 and 0.71 for the prediction of clinically nonimportant cancer. Clinical stage T1c prostate cancers are heterogeneous in pathologic stage and volume. MR imaging may

  6. The dynamics of accumulation and disappearance of 89Sr in tea

    International Nuclear Information System (INIS)

    Chen Chuanqun; Wang Shouxiang; Zhang Yongxi; Sun Zhiming

    1994-06-01

    The 89 Sr was put into a tea tree-soil system by different ways. The results showed that for 89 Sr put into the system through the above-ground 1 part of tea tree, its concentration in tea was much higher than that through soil. The concentration of 89 Sr in older tea was higher than that in shoot for the same treatment. The accumulation and disappearance of 89 Sr in tea varied with the treatments. For the treatment through the above-ground part, the concentrations of 89 Sr in older tea and shoot were monotonously decreasing with time. For the treatment through soil the concentration of 89 Sr in shoot increased initially to a maximum value, then decreased slowly; while the concentration of 89 Sr in older tea increased quickly in a definite period, then increased slowly to gain a saturated value. In addition, the values of concentration factor of 89 Sr in the older tea and shoot were determined, too

  7. Anticancer activity and potential mechanisms of 1C, a ginseng saponin derivative, on prostate cancer cells

    Directory of Open Access Journals (Sweden)

    Xu De Wang

    2018-04-01

    Full Text Available Background: AD-2 (20(R-dammarane-3b, 12b, 20, 25-tetrol; 25-OH-PPD is a ginsenoside and isolated from Panax ginseng, showing anticancer activity against extensive human cancer cell lines. In this study, effects and mechanisms of 1C ((20R-3b-O-(L-alanyl-dammarane-12b, 20, 25-triol, a modified version of AD-2, were evaluated for its development as a novel anticancer drug. Methods: MTT assay was performed to evaluate cell cytotoxic activity. Cell cycle and levels of reactive oxygen species (ROS were determined using flow cytometry analysis. Western blotting was employed to analyze signaling pathways. Results: 1C concentration-dependently reduces prostate cancer cell viability without affecting normal human gastric epithelial cell line-1 viability. In LNCaP prostate cancer cells, 1C triggered apoptosis via Bcl-2 family-mediated mitochondria pathway, downregulated expression of mouse double minute 2, upregulated expression of p53 and stimulated ROS production. ROS scavenger, N-acetylcysteine, can attenuate 1C-induced apoptosis. 1C also inhibited the proliferation of LNCaP cells through inhibition on Wnt/β-catenin signaling pathway. Conclusion: 1C shows obvious anticancer activity based on inducing cell apoptosis by Bcl-2 family-mediated mitochondria pathway and ROS production, inhibiting Wnt/β-catenin signaling pathway. These findings demonstrate that 1C may provide leads as a potential agent for cancer therapy. Keywords: 1C, AD-2, apoptosis, reactive oxygen species, Wnt/β-catenin pathway

  8. Down-regulation of S100C is associated with bladder cancer progression and poor survival

    DEFF Research Database (Denmark)

    Memon, Ashfaque Ahmed; Sorensen, Boe Sandahl; Meldgaard, Peter

    2005-01-01

    cancer biopsy samples obtained from 88 patients followed for a median of 23 months (range, 1-97 months). RESULTS: We found a significantly lower mRNA expression of S100C in connective tissue invasive tumors (T1, P = 0.0030) and muscle invasive tumors [(T2-T4), P ...PURPOSE: The goal of this study was to identify proteins down-regulated during bladder cancer progression. EXPERIMENTAL DESIGN: By using comparative proteome analysis and measurement of mRNA, we found a significant down-regulation of S100C, a member of the S100 family of proteins, in T24 (grade 3......) as compared with RT4 (grade 1) bladder cancer cell lines. Moreover, quantification of the mRNA level revealed that decreased expression of the protein reflects a low level of transcription of the S100C gene. Based on this observation, we quantified the S100C mRNA expression level with real-time PCR in bladder...

  9. A dietary pattern that is associated with C-peptide and risk of colorectal cancer in women.

    Science.gov (United States)

    Fung, Teresa T; Hu, Frank B; Schulze, Matthias; Pollak, Michael; Wu, Tianying; Fuchs, Charles S; Giovannucci, Edward

    2012-06-01

    Higher serum C-peptide concentrations have shown to be associated with an increased risk of colorectal cancer (CRC). Therefore, we used diet information to identify food groups that correlated with fasting serum concentrations of C-peptide and assess the association of this dietary pattern and CRC risk. Major food contributors to fasting C-peptide concentrations were identified with stepwise linear regression in a subsample (n = 833) of women from a large cohort. We then summed the consumption frequency of the major food contributors to form a C-peptide dietary pattern for the entire cohort (n = 66,714). Risk for CRC was computed using Cox proportional hazard model with the C-peptide dietary pattern score as the predictor. In up to 20 years of follow-up, we ascertained 985 cases of CRC and 758 colon cancer. After adjusting for confounders, the C-peptide dietary pattern, characterized by higher meat, fish, and sweetened beverage intake, but lower coffee, high fat dairy, and whole grains intake, showed direct association with CRC risk (RR comparing extreme quintiles = 1.29, 95 % CI = 1.05-1.58, p trend = 0.048). The same comparison was slightly stronger for colon cancer (RR = 1.35, 95 % CI = 1.07-1.70, p trend = 0.009). In stratified analysis, there was no association between the C-peptide dietary pattern and colon cancer among lean and active women. However, for overweight or sedentary women, RR for the same comparison was 1.58 (95 % CI = 1.20-2.07, p trend = 0.002) (p for interaction = 0.007). We derived a dietary pattern that correlated with C-peptide concentrations. This pattern was associated with an increase in colon cancer, especially among women who were overweight or sedentary.

  10. The influence of family history of cancer, irradiation and anticancer medication (mitomycin C), on the occurrence of multiple primary neoplasms with breast cancer

    International Nuclear Information System (INIS)

    Yoshimoto, Masataka; Kasumi, Fujio; Fukami, Atsuo; Nishi, Mitsumasa; Kajitani, Tamaki; Sakamoto, Goi

    1985-01-01

    The influence of family history of cancer, radiation therapy and anticancer drug therapy (mitomycin C) on the occurrence of multiple primary neoplasms, following treatment of a first primary cancer of the breast, was analyzed by the person-year method in 1,359 patients, in Japan. During 14,371.8 person-years of observation, 111 multiple primary neoplasms including bilateral breast cancers were found in 109 patients. The incidence rate of multiple primary neoplasms were 0.00772 per person-year. The incidence in patients with a family history of cancer was 1.29 times greater than that in patients without such a family history, and the incidence in patients with a family history of breast cancer was about three times greater than that in those without it (p < 0.01). Radiation therapy raised the occurrence of subsequent primary neoplasms 1.28-fold (or 1.62 fold after 5 years), and mitomycin C (a total dose of 0.8 mg/kg) therapy caused no increase in the occurrence of subsequent primary cancers, after an observation of 10 years or so. (author)

  11. Dicty_cDB: Contig-U12564-1 [Dicty_cDB

    Lifescience Database Archive (English)

    Full Text Available 498178_1( DQ498178 |pid:none) Human rotavirus A isolate rj5323/0... 35 8.9 BA000043_332( BA000043 |pid:none)...stoc punctiforme PCC 73102, c... 35 8.9 DQ498183_1( DQ498183 |pid:none) Human rotavirus A isolate rj5619/0..

  12. 40 CFR 89.126 - Denial, revocation of certificate of conformity.

    Science.gov (United States)

    2010-07-01

    ... conformity. 89.126 Section 89.126 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR... Standards and Certification Provisions § 89.126 Denial, revocation of certificate of conformity. (a) If... issued certificate of conformity if the Administrator finds any one of the following infractions to be...

  13. Quality control methods of strontium chloride 89SrCl2, radiopharmaceutical for palliative treatment of bone metastases

    International Nuclear Information System (INIS)

    Deptula, C.Z.; Kempisty, T.; Markiewicz, A.; Mikolajczak, R.; Stefancyk, S.; Terlikowska, T.; Zulczyk, W.

    1997-01-01

    Strontium chloride, 89 SrCI 2 , a radiopharmaceutical used for palliative therapy of bone metastases from breast and prostate cancer is produced by irradiation in a nuclear reactor. The analytical quality control procedures are established to confirm the radionuclidic purity of the preparation, its chemical composition and specific activity. Chemical concentration of strontium in the product is determined by complexometry with arsenazo III and chlorides assay by potentiometric titration with silver nitrate. The contamination with chemical impurities is determined by DC graphite spark spectrography. The specific activity and isotonicity of the solution are corrected by addition of natural SrCI 2 and NaCI. 90 Sr is produced in the 89 Sr(n,γ) 90 Sr reaction contributes to impurities. It decays to 90 Y and the activity of 90 Sr can be calculated from the activity of 90 Y. The extraction chromatography on nonionic acrylic ester polymer coated with organic solutions of selective features (Spec resins for Eichrom) is applied for separation of radionuclides. The extraction chromatography system consisting of two columns: strontium selective resin and rare earth elements selective resin was used for separation of 90 Y from 90 Sr in the 89 SrCI 2 solution. The 90 Y and 90 Sr carrier-free solutions used as tracers helped for determination of extraction conditions and efficiency. The concentration of 90 Sr determined in the analysed solution is at the level of 2.10 -4 % which conforms with the data calculated from irradiation parameters. The obtained product, strontium chloride 89 SrCI 2 for injection, forms a sterile and isotonic water solution (pH - 4-7) with specific activity of 89 Sr in the range from 3.5 to 6.3. MBq/mg and radioactive concentration of 37.5 MBq/ml. The radionuclidic purity of the obtained preparations is at the level of 99.9% with respect to 89 Sr

  14. Combination therapy with hormonal, radiation and chemotherapy for stage C prostate cancer

    International Nuclear Information System (INIS)

    Iwasawa, Toshihisa; Matsumoto, Hidetsugu

    1996-01-01

    To improve the effectiveness of treatment for patients with stage C prostate cancer, therapy in combination with hormonal, radiation and chemotherapy was given for the initial period, and there after, hormonal therapy was continuously administered to 18 patients with chemotherapy and three patients without it. At the Social Health Insurance Medical Center, between May 1988 and August 1991, 21 patients were diagnosed to have stage C histologically confirmed adenocarcinoma of the prostate. The average age of the patients was 69.0 years. The tumor was well, moderate and poorly differentiated in 5, 6 and 10 patients, respectively. As hormonal therapy, orchiectomy was performed on 19 of the 21 patients. Furthermore, 11 patients were administered estramustine phosphate, 9 chlormadinone acetate, and one diethylstilbesterol diphosphate. As, radiation therapy, all patients were treated with AP-PA parallel opposing technique to small pelvis with a 12 cm x 12 cm treatment field (44-45 Gy) combined with conformation radiotherapy to prostate (20-26 Gy). Chemotherapy was performed using either one or a combination of the following; cis-diamminedichloroplatinum, adriamycin, cyclophosphamide, 5-fluorouracil, methotrexate and etoposide. The observation period was 54.5 months on the average. Recurrence was observed in 3 patients, for all of which the sites were at bone. The 5-year non-recurrence rate was 90.4% by Kaplan-Meier's method. There were 4 deaths, three were due to prostate cancer and one to gastric cancer. The 5-year cumulative survival rate by Kaplan-Meier's method was 90.5%. In conclusion, this treatment was effective for stage C cases of prostate cancer. (author)

  15. Threonine 89 Is an Important Residue of Profilin-1 That Is Phosphorylatable by Protein Kinase A.

    Directory of Open Access Journals (Sweden)

    David Gau

    Full Text Available Dynamic regulation of actin cytoskeleton is at the heart of all actin-based cellular events. In this study, we sought to identify novel post-translational modifications of Profilin-1 (Pfn1, an important regulator of actin polymerization in cells.We performed in vitro protein kinase assay followed by mass-spectrometry to identify Protein Kinase A (PKA phosphorylation sites of Pfn1. By two-dimensional gel electrophoresis (2D-GE analysis, we further examined the changes in the isoelectric profile of ectopically expressed Pfn1 in HEK-293 cells in response to forskolin (FSK, an activator of cAMP/PKA pathway. Finally, we combined molecular dynamics simulations (MDS, GST pull-down assay and F-actin analyses of mammalian cells expressing site-specific phosphomimetic variants of Pfn1 to predict the potential consequences of phosphorylation of Pfn1.We identified several PKA phosphorylation sites of Pfn1 including Threonine 89 (T89, a novel site. Consistent with PKA's ability to phosphorylate Pfn1 in vitro, FSK stimulation increased the pool of the most negatively charged form of Pfn1 in HEK-293 cells which can be attenuated by PKA inhibitor H89. MDS predicted that T89 phosphorylation destabilizes an intramolecular interaction of Pfn1, potentially increasing its affinity for actin. The T89D phosphomimetic mutation of Pfn1 elicits several changes that are hallmarks of proteins folded into alternative three-dimensional conformations including detergent insolubility, protein aggregation and accelerated proteolysis, suggesting that T89 is a structurally important residue of Pfn1. Expression of T89D-Pfn1 induces actin:T89D-Pfn1 co-clusters and dramatically reduces overall actin polymerization in cells, indicating an actin-sequestering action of T89D-Pfn1. Finally, rendering T89 non-phosphorylatable causes a positive charge shift in the isoelectric profile of Pfn1 in a 2D gel electrophoresis analysis of cell extracts, a finding that is consistent with

  16. Human RNA polymerase II associated factor 1 complex promotes tumorigenesis by activating c-MYC transcription in non-small cell lung cancer

    International Nuclear Information System (INIS)

    Zhi, Xiuyi; Giroux-Leprieur, Etienne; Wislez, Marie; Hu, Mu; Zhang, Yi; Shi, Huaiyin; Du, Kaiqi; Wang, Lei

    2015-01-01

    Human RNA polymerase II (RNAPII)-associated factor 1 complex (hPAF1C) plays a crucial role in protein-coding gene transcription. Overexpression of hPAF1C has been implicated in the initiation and progression of various human cancers. However, the molecular pathways involved in tumorigenesis through hPAF1C remain to be elucidated. The current study suggested hPAF1C expression as a prognostic biomarker for early stage non-small cell lung cancer (NSCLC) and patients with low hPAF1C expression levels had significantly better overall survival. Furthermore, the expression of hPAF1C was found to be positively correlated with c-MYC expression in patient tumor samples and in cancer cell lines. Mechanistic studies indicated that hPAF1C could promote lung cancer cell proliferation through regulating c-MYC transcription. These results demonstrated the prognostic value of hPAF1C in early-stage NSCLC and the role of hPAF1C in the transcriptional regulation of c-MYC oncogene during NSCLC tumorigenesis. - Highlights: • hPAF1C expression is a prognostic biomarker for early stage non-small cell lung cancer. • The expression of hPAF1C was positively correlated with c-MYC in tumor samples of patients and in several NSCLC cell lines. • hPAF1C could promote lung cancer cell proliferation through regulating c-MYC transcription.

  17. The cGAS-cGAMP-STING pathway connects DNA damage to inflammation, senescence, and cancer.

    Science.gov (United States)

    Li, Tuo; Chen, Zhijian J

    2018-05-07

    Detection of microbial DNA is an evolutionarily conserved mechanism that alerts the host immune system to mount a defense response to microbial infections. However, this detection mechanism also poses a challenge to the host as to how to distinguish foreign DNA from abundant self-DNA. Cyclic guanosine monophosphate (GMP)-adenosine monophosphate (AMP) synthase (cGAS) is a DNA sensor that triggers innate immune responses through production of the second messenger cyclic GMP-AMP (cGAMP), which binds and activates the adaptor protein STING. However, cGAS can be activated by double-stranded DNA irrespective of the sequence, including self-DNA. Although how cGAS is normally kept inactive in cells is still not well understood, recent research has provided strong evidence that genomic DNA damage leads to cGAS activation to stimulate inflammatory responses. This review summarizes recent findings on how genomic instability and DNA damage trigger cGAS activation and how cGAS serves as a link from DNA damage to inflammation, cellular senescence, and cancer. © 2018 Li and Chen.

  18. Results of lung cancer screening in atomic bomb survivors

    International Nuclear Information System (INIS)

    Yamashita, Masayo; Kato, Hironari; Inoue, Noriko; Naito, Kumiko; Kawanishi, Masahiro; Kira, Sakurako; Sasaki, Hideo; Ishida, Hajime; Maeda, Ryo

    2012-01-01

    Risk of lung cancer in A-bomb survivors is reportedly increased. The screening in the title has been conducted since 1988 and this report summarizes its results of the latest 6-year term (2004-2009). The total number of subjects who visited authors' facility for the screening in the period was 39,147 men (average age 70.6 y) and 45,351 women (71.8 y), of the age range of 60-89 y. The screening results of the cancer were examined concerning with sex, age and exposure situation. As well, the relationship between the found cancer incidence and exposure in never, formerly and currently smoking subjects were also examined. Exposure situation was divided in 3 groups of the exposure by entrance in the city/by other reasons, within 2 km close (Close, C) to, and out of 2.1 km afar (Distant, D) from, the city. Statistic analysis was performed by Chi-squire and/or Fisher's exact test. The index of positive finding in the screening of the lung cancer per 1,000 subjects was the highest in C men of ages 70s, 2.88 subjects, which was statistically significant from 0.85 in D men of the same generation. In current smokers, the index 5.40 in C men of ages 70s was significantly higher than 0.90 in D men of the same generation. Overall, positive results tended to be high in survivors of C regardless to sex and smoking, and was significantly high in current smokers of C as above, both implying the particular necessity of promotion to stop smoking in survivors. (T.T.)

  19. Genetic polymorphism 609C>T in NAD(P)H:quinone oxidoreductase 1 enhances the risk of proximal colon cancer

    NARCIS (Netherlands)

    Freriksen, J.J.; Salomon, J.; Roelofs, H.M.; Morsche, R.H. te; Stappen, J.W. van der; Dura, P.; Witteman, B.J.; Lacko, M.; Peters, W.H.

    2014-01-01

    Gastrointestinal (GI) cancer is responsible for the majority of deaths among all types of cancer. Lifestyle factors may not only be the main risk factor for GI cancer but reactive oxygen species (ROS) may also be involved. The single-nucleotide polymorphisms (SNPs) 609C>T (rs1800566) and 465C>T

  20. Proteomic profiling of mammary carcinomas identifies C7orf24, a gamma-glutamyl cyclotransferase, as a potential cancer biomarker

    DEFF Research Database (Denmark)

    Gromov, Pavel; Gromova, Irina; Friis, Esbern

    2010-01-01

    Breast cancer is the leading cause of cancer deaths in women today and is the most common cancer (excluding skin cancers) among women in the Western world. Although cancers detected by screening mammography are significantly smaller than nonscreening ones, noninvasive biomarkers for detection...... in different types of cancer suggests deregulation of C7orf24 to be a general event in epithelial carcinogenesis, indicating that this protein may play an important role in cancer cell biology and thus constitute a novel therapeutic target. Furthermore, as C7orf24 is externalized to the tissue extracellular...... fluid and can be detected in serum, this protein also represents a potential serological marker....

  1. Plasma and dietary carotenoids and vitamins A, C and E and risk of colon and rectal cancer in the European Prospective Investigation into Cancer and Nutrition

    NARCIS (Netherlands)

    Leenders, M.; Leufkens, A.M.; Siersema, P.D.; Duijnhoven, F.J.B. van; Vrieling, A.; Hulshof, P.J.; Gils, C.H. van; Overvad, K.; Roswall, N.; Kyro, C.; Boutron-Ruault, M.C.; Fagerhazzi, G.; Cadeau, C.; Kuhn, T.; Johnson, T.; Boeing, H.; Aleksandrova, K.; Trichopoulou, A.; Klinaki, E.; Androulidaki, A.; Palli, D.; Grioni, S.; Sacerdote, C.; Tumino, R.; Panico, S.; Bakker, M.F.; Skeie, G.; Weiderpass, E.; Jakszyn, P.; Barricarte, A.; Huerta, J. Maria; Molina-Montes, E.; Arguelles, M.; Johansson, I.; Ljuslinder, I.; Key, T.J.; Bradbury, K.E.; Khaw, K.T.; Wareham, N.J.; Ferrari, P.; Duarte-Salles, T.; Jenab, M.; Gunter, M.J.; Vergnaud, A.C.; Wark, P.A.; Bueno-De-Mesquita, H.B.

    2014-01-01

    Carotenoids and vitamins A, C and E are possibly associated with a reduced colorectal cancer (CRC) risk through antioxidative properties. The association of prediagnostic plasma concentrations and dietary consumption of carotenoids and vitamins A, C and E with the risk of colon and rectal cancer was

  2. Plasma and dietary carotenoids and vitamins A, C and e and risk of colon and rectal cancer in the European Prospective Investigation into Cancer and Nutrition

    NARCIS (Netherlands)

    Leenders, Max; Leufkens, Anke M.; Siersema, Peter D.; Van Duijnhoven, Fränzel J B; Vrieling, Alina; Hulshof, Paul J M; Van Gils, Carla H.; Overvad, Kim; Roswall, Nina; Kyrø, Cecilie; Boutron-Ruault, Marie Christine; Fagerhazzi, Guy; Cadeau, Claire; Kühn, Tilman; Johnson, Theron; Boeing, Heiner; Aleksandrova, Krasimira; Trichopoulou, Antonia; Klinaki, Eleni; Androulidaki, Anna; Palli, Domenico; Grioni, Sara; Sacerdote, Carlotta; Tumino, Rosario; Panico, Salvatore; Bakker, Marije F.; Skeie, Guri; Weiderpass, Elisabete; Jakszyn, Paula; Barricarte, Aurelio; Huerta, José María; Molina-Montes, Esther; Argüelles, Marcial; Johansson, Ingegerd; Ljuslinder, Ingrid; Key, Timothy J.; Bradbury, Kathryn E.; Khaw, Kay Tee; Wareham, Nicholas J.; Ferrari, Pietro; Duarte-Salles, Talita; Jenab, Mazda; Gunter, Marc J.; Vergnaud, Anne Claire; Wark, Petra A.; Bueno-de-Mesquita, H. B.

    2014-01-01

    Carotenoids and vitamins A, C and E are possibly associated with a reduced colorectal cancer (CRC) risk through antioxidative properties. The association of prediagnostic plasma concentrations and dietary consumption of carotenoids and vitamins A, C and E with the risk of colon and rectal cancer was

  3. Elevated C1orf63 expression is correlated with CDK10 and predicts better outcome for advanced breast cancers: a retrospective study

    International Nuclear Information System (INIS)

    Hong, Chao-Qun; Zhang, Fan; You, Yan-Jie; Qiu, Wei-Li; Giuliano, Armando E.; Cui, Xiao-Jiang; Zhang, Guo-Jun; Cui, Yu-Kun

    2015-01-01

    Chromosome 1 open reading frame 63 (C1orf63) is located on the distal short arm of chromosome 1, whose allelic loss has been observed in several human cancers. C1orf63 has been reported to be up-regulated in IL-2-starved T lymphocytes, which suggests it might be involved in cell cycle control, a common mechanism for carcinogenesis. Here we investigated the expression and clinical implication of C1orf63 in breast cancer. Paraffin-embedded specimens, clinicopathological features and follow-up data of the breast cancer patients were collected. Publicly available microarray and RNA-seq datasets used in this study were downloaded from ArrayExpress of EBI and GEO of NCBI. KM plotter tool was also adopted. The expression of C1orf63 and CDK10, one known cell cycle-dependent tumor suppressor in breast cancer, was assessed by immunohistochemistry. Western blotting was performed to detect C1orf63 protein in human breast cancer cell lines, purchased from the Culture Collection of the Chinese Academy of Sciences, Shanghai. In a group of 12 human breast tumors and their matched adjacent non-cancerous tissues, C1orf63 expression was observed in 7 of the 12 breast tumors, but not in the 12 adjacent non-cancerous tissues (P < 0.001). Similar results were observed of C1orf63 mRNA expression both in breast cancer and several other cancers, including lung cancer, prostate cancer and hepatocellular carcinoma. In another group of 182 breast cancer patients, C1orf63 expression in tumors was not correlated with any clinicopathological features collected in this study. Survival analyses showed that there was no significant difference of overall survival (OS) rates between the C1orf63 (+) group and the C1orf63 (−) group (P = 0.145). However, the analyses of KM plotter displayed a valid relationship between C1orf63 and RFS (relapse free survival)/OS (P < 0.001; P = 0.007). Notablely, in breast cancers with advanced TNM stages (III ~ IV) among these 182 patients, C1orf63 expression was an

  4. Optimized anion exchange column isolation of zirconium-89 ( 89 Zr) from yttrium cyclotron target: Method development and implementation on an automated fluidic platform

    Energy Technology Data Exchange (ETDEWEB)

    O’Hara, Matthew J.; Murray, Nathaniel J.; Carter, Jennifer C.; Morrison, Samuel S.

    2018-04-01

    Zirconium-89 (89Zr), produced by the (p,n) reaction from naturally monoisotopic yttrium (natY), is a promising positron emitting isotope for immunoPET imaging. Its long half-life of 78.4 h is sufficient for evaluating slow physiological processes. A prototype automated fluidic system, coupled to on-line and in-line detectors, has been constructed to facilitate development of new 89Zr purification methodologies. The highly reproducible reagent delivery platform and near-real time monitoring of column effluents allows for efficient method optimization. The separation of Zr from dissolved Y metal targets was evaluated using several anion exchange resins. Each resin was evaluated against its ability to quantitatively capture Zr from a load solution that is high in dissolved Y. The most appropriate anion exchange resin for this application was identified, and the separation method was optimized. The method is capable of a high Y decontamination factor (>105) and has been shown to separate Fe, an abundant contaminant in Y foils, from the 89Zr elution fraction. Finally, the performance of the method was evaluated using cyclotron bombarded Y foil targets. The separation method was shown to achieve >95% recovery of the 89Zr present in the foils. The 89Zr eluent, however, was in a chemical matrix not immediately conducive to labeling onto proteins. The main intent of this study was to develop a tandem column 89Zr purification process, wherein the anion exchange column method described here is the first separation in a dual-column purification process.

  5. Evaluation of the antitumor effects of c-Myc-Max heterodimerization inhibitor 100258-F4 in ovarian cancer cells.

    Science.gov (United States)

    Wang, Jiandong; Ma, Xiaoli; Jones, Hannah M; Chan, Leo Li-Ying; Song, Fang; Zhang, Weiyuan; Bae-Jump, Victoria L; Zhou, Chunxiao

    2014-08-21

    Epithelial ovarian carcinoma is the most lethal gynecological cancer due to its silent onset and recurrence with resistance to chemotherapy. Overexpression of oncogene c-Myc is one of the most frequently encountered events present in ovarian carcinoma. Disrupting the function of c-Myc and its downstream target genes is a promising strategy for cancer therapy. Our objective was to evaluate the potential effects of small-molecule c-Myc inhibitor, 10058-F4, on ovarian carcinoma cells and the underlying mechanisms by which 10058-F4 exerts its actions. Using MTT assay, colony formation, flow cytometry and Annexin V FITC assays, we found that 10058-F4 significantly inhibited cell proliferation of both SKOV3 and Hey ovarian cancer cells in a dose dependent manner through induction of apoptosis and cell cycle G1 arrest. Treatment with 10058-F4 reduced cellular ATP production and ROS levels in SKOV3 and Hey cells. Consistently, primary cultures of ovarian cancer treated with 10058-F4 showed induction of caspase-3 activity and inhibition of cell proliferation in 15 of 18 cases. The response to 10058-F4 was independent the level of c-Myc protein over-expression in primary cultures of ovarian carcinoma. These novel findings suggest that the growth of ovarian cancer cells is dependent upon c-MYC activity and that targeting c-Myc-Max heterodimerization could be a potential therapeutic strategy for ovarian cancer.

  6. Production, applications and status of zirconium-89 immunoPET agents

    International Nuclear Information System (INIS)

    Jalilian, A.R.; Osso, Joao Alberto

    2017-01-01

    Zirconium-89 has attracted huge interests and is used in tracing and quantification of slow biological processes and labeling of long half-live biomolecules such as monoclonal antibodies for pharmacokinetic studies and clinical trials. In this review, a concise introduction to targetry, irradiation data, separation and coordination chemistry of zirconium-89 has been presented. A detailed overreviwew on bi-functional ligands conjugation and "8"9Zr radiolabeling been addressed. The latest status of preclinical as well as clinical trials using "8"9Zr radioimmunomolecules in various human diseases has been presented since 2012. (author)

  7. Construction of a T7 Human Lung Cancer cDNA Library

    Directory of Open Access Journals (Sweden)

    Wentao YUE

    2008-10-01

    Full Text Available Background and objective Currently, only a limited numbers of tumor markers for non small lung cancer (NSCLC diagnosis, new biomarker, such as serum autoantibody may improve the early detection of lung cancer. Our objective is construction human lung squamous carcinoma and adenocarcinoma T7 phage display cDNA library from the tissues of NSCLC patients. Methods mRNA was isolated from a pool of total RNA extract from NSCLC tissues obtained from 5 adenocarcinomas and 5 squamous carcinomas, and then mRNA was reverse transcribed into double stranded cDNA. After digestion, the cDNA was inserted into T7Select 10-3 vector. The phage display cDNA library was constructed by package reaction in vitro and plate proliferation. Plaque assay and PCR were used to evaluate the library.Results Two T7 phage display cDNA library were established. Plaque assay show the titer of lung squamas carcinoma library was 1.8×106 pfu, and the adenocarcinoma library was 5×106 pfu. The phage titer of the amplified library were 3.2×1010 pfu/mL and 2.5×1010 pfu/mL. PCR amplification of random plaque show insert ratio were 100% (24/24 in adenocarcinoma library and 95.8% in human lung squamas carcinoma library (23/24. Insert range from 300 bp to 1 500 bp. Conclusion Two phage display cDNA library from NSCLC were constructed.

  8. Tratamento cirúrgico do câncer colorretal: resultados a longo prazo e análise da qualidade Surgical treatment of colorectal cancer: long term results and quality control

    Directory of Open Access Journals (Sweden)

    Mauro de Souza Leite Pinho

    2006-12-01

    Full Text Available A obtenção de resultados cada vez melhores no tratamento do câncer colorretal apresenta-se hoje como um desafio devido à sua crescente prevalência em todo o mundo. Diversos estudos têm demonstrado que a qualidade do tratamento cirúrgico instituído representa um dos principais fatores prognósticos, podendo ser esta avaliada através de aspectos como mortalidade operatória, preservação esfincteriana, recorrência local e sobrevida. O objetivo do presente trabalho é apresentar os resultados obtidos a longo prazo no tratamento cirúrgico do câncer colorretal pelo Grupo de Coloproctologia do Departamento de Cirurgia do Hospital Municipal São José, em Joinville, e confrontá-los com a literatura a respeito, visando obter uma avaliação crítica da qualidade do tratamento instituído. Foi realizada uma análise prospectiva de uma série consecutiva de 97 pacientes submetidos ao tratamento cirúrgico do câncer colorretal, com perspectivas curativas e tempo de seguimento médio de 80,8 meses. Foi observada mortalidade operatória em seis pacientes (6,1%, recidiva local para câncer retal e colônico em seis (12,5% e quatro (9,7% pacientes, respectivamente, e a necessidade de realização de colostomia definitiva no câncer retal em 14 casos (27%. A sobrevida geral média foi de 48,9 meses. A sobrevida geral de cinco anos para o seguimento oncológico (n=63 foi de 52%, sendo 89% para pacientes estágio 1, 70% para pacientes estágio 2 e 20% para pacientes estágio 3. Concluímos que o tratamento instituído encontra-se dentro dos padrões aceitáveis do ponto de vista da literatura, demonstrando, no entanto, a necessidade de aprimoramento em alguns aspectos específicos.Improvement of results in treatment of colorectal cancer remains a major challenge due to its increasing worldwide prevalence. Several studies have demonstrated the quality of surgical treatment as one of the most important prognostic factors, assessed by parameters such

  9. 22 CFR 92.89 - Fees for service of legal process.

    Science.gov (United States)

    2010-04-01

    ... 22 Foreign Relations 1 2010-04-01 2010-04-01 false Fees for service of legal process. 92.89 Section 92.89 Foreign Relations DEPARTMENT OF STATE LEGAL AND RELATED SERVICES NOTARIAL AND RELATED SERVICES Quasi-Legal Services § 92.89 Fees for service of legal process. No charge should be made for...

  10. Risco de câncer de pulmão, laringe e esôfago atribuível ao fumo Attributed risk to smoking for lung cancer, laryngeal cancer and esophageal cancer

    Directory of Open Access Journals (Sweden)

    Ana MB Menezes

    2002-04-01

    Full Text Available OBJETIVO: Os tipos de câncer de pulmão, laringe e esôfago têm como um de seus principais fatores de risco o fumo. O objetivo do estudo foi avaliar o risco populacional atribuível ao fumo nesses tipos de câncer. MÉTODOS: A pesquisa baseou-se em três estudos de caso-controle em cidade de médio porte do Brasil. Analisaram-se casos incidentes hospitalares de câncer de pulmão, de laringe e de esôfago diagnosticados por biópsias; os controles foram pacientes hospitalizados por outros motivos, sem ser câncer ou doenças altamente relacionadas ao fumo. O fator de exposição foi o tabagismo medido em três níveis: não-fumantes, ex-fumantes e fumantes atuais, definidos por meio de questionários aplicados por entrevistadores treinados. Para a medida de efeito, foi utilizado o odds ratio obtendo-se, dessa forma, o "risco populacional atribuível" ao fumo com IC de 95%. RESULTADOS: Foram estudados 122 casos e 244 controles de câncer de pulmão, 50 casos de câncer de laringe e 48 casos de câncer de esôfago, com um grupo de 96 controles comum a ambos. A prevalência da exposição ao fumo utilizada para a análise foi de 34%, que corresponde à prevalência de fumo na população adulta da cidade. Os odds ratios para o cálculo do risco populacional atribuível foram obtidos por análises ajustadas para os fatores de confusão de cada um dos estudos. Para ex-fumantes com câncer de pulmão, o risco populacional atribuível foi de 63% (IC95%, 0,58-0,68 e, para fumantes, de 71% (IC95%, 0,65-0,77. Para câncer de laringe, o RPA foi de 74% (IC95%, 0,70-0,78 para ex-fumantes e de 86% (IC95%, 0,81-0,85 para fumantes. O câncer de esôfago mostrou um risco de 54% (IC95%, 0,46-0,62 para fumantes. CONCLUSÃO: Conclui-se que o fumo é um importante fator de risco e que a cessação do mesmo contribuiria para reduções significativas na incidência de câncer nesses três sítios.OBJECTIVE:Lung, laryngeal and esophageal cancers have smoking as one

  11. Mortalidad por cáncer en los mineros del mercurio Cancer mortality in mercury miners

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    Montserrat García Gómez

    2007-06-01

    Full Text Available Objetivos: Analizar la mortalidad por cáncer en una cohorte de mineros del mercurio. Métodos: Estudiamos la mortalidad por cáncer de 3.998 mineros expuestos a mercurio de Minas de Almadén y Arrayanes, S.A. El período de seguimiento comprendió desde 1895 hasta 1994. Se determinó el estado vital y la causa básica de defunción. Se calcularon las razones de mortalidad estandarizadas (RME según la edad, el sexo y el período de calendario. Las muertes esperadas se obtuvieron de las tasas específicas españolas. Resultados: Se determinó el estado vital del 92% de los trabajadores: 1.786 estaban vivos en 1994 (49%, 1.535 habían muerto (42% y de 327 no pudo conocerse el estado vital (8%. La mortalidad por cáncer fue significativamente menor de la esperada (RME de 0,72; intervalo de confianza del 95%, 0,63-0,82, y se encontró el déficit principalmente en los cánceres de colon y vejiga. Se encontró un pequeño exceso en la mortalidad por cáncer de hígado, para el que se registraron 20 muertes, mientras se esperaban 17. La mortalidad por cáncer de pulmón y del sistema nervioso central fue prácticamente igual a la esperada; la mortalidad por cáncer de riñón fue menor de la esperada. Se observó una tendencia positiva en la mortalidad por todos los tipos de cáncer con la duración de la exposición. Conclusiones: Esta investigación aporta evidencias adicionales de la ausencia de un aumento sustancial del riesgo de cáncer en los trabajadores expuestos al mercurio inorgánico.Objectives: To analyze cancer mortality in a cohort of mercury miners. Methods: Cancer mortality in 3,998 workers exposed to mercury in Minas de Almadén y Arrayanes S.A. was studied. The follow-up period was from 1895 to 1994. Vital status and the basic cause of death, in the case of fatalities, were determined. Standardized mortality ratios (SMR by age, sex and calendar period were calculated. Expected deaths were obtained from age, sex and calendar period

  12. c-Myc activates BRCA1 gene expression through distal promoter elements in breast cancer cells

    International Nuclear Information System (INIS)

    Chen, Yinghua; Xu, Jinhua; Borowicz, Stanley; Collins, Cindy; Huo, Dezheng; Olopade, Olufunmilayo I

    2011-01-01

    The BRCA1 gene plays an important role in the maintenance of genomic stability. BRCA1 inactivation contributes to breast cancer tumorigenesis. An increasing number of transcription factors have been shown to regulate BRCA1 expression. c-Myc can act as a transcriptional activator, regulating up to 15% of all genes in the human genome and results from a high throughput screen suggest that BRCA1 is one of its targets. In this report, we used cultured breast cancer cells to examine the mechanisms of transcriptional activation of BRCA1 by c-Myc. c-Myc was depleted using c-Myc-specific siRNAs in cultured breast cancer cells. BRCA1 mRNA expression and BRCA1 protein expression were determined by quantitative RT-PCR and western blot, respectively and BRCA1 promoter activities were examined under these conditions. DNA sequence analysis was conducted to search for high similarity to E boxes in the BRCA1 promoter region. The association of c-Myc with the BRCA1 promoter in vivo was tested by a chromatin immunoprecipitation assay. We investigated the function of the c-Myc binding site in the BRCA1 promoter region by a promoter assay with nucleotide substitutions in the putative E boxes. BRCA1-dependent DNA repair activities were measured by a GFP-reporter assay. Depletion of c-Myc was found to be correlated with reduced expression levels of BRCA1 mRNA and BRCA1 protein. Depletion of c-Myc decreased BRCA1 promoter activity, while ectopically expressed c-Myc increased BRCA1 promoter activity. In the distal BRCA1 promoter, DNA sequence analysis revealed two tandem clusters with high similarity, and each cluster contained a possible c-Myc binding site. c-Myc bound to these regions in vivo. Nucleotide substitutions in the c-Myc binding sites in these regions abrogated c-Myc-dependent promoter activation. Furthermore, breast cancer cells with reduced BRCA1 expression due to depletion of c-Myc exhibited impaired DNA repair activity. The distal BRCA1 promoter region is associated with c

  13. Cav1.2 channel current block by the PKA inhibitor H-89 in rat tail artery myocytes via a PKA-independent mechanism: Electrophysiological, functional, and molecular docking studies.

    Science.gov (United States)

    Fusi, Fabio; Trezza, Alfonso; Spiga, Ottavia; Sgaragli, Giampietro; Bova, Sergio

    2017-09-15

    To characterize the role of cAMP-dependent protein kinase (PKA) in regulating vascular Ca 2+ current through Ca v 1.2 channels [I Ca1.2 ], we have documented a marked capacity of the isoquinoline H-89, widely used as a PKA inhibitor, to reduce current amplitude. We hypothesized that the I Ca1.2 inhibitory activity of H-89 was mediated by mechanisms unrelated to PKA inhibition. To support this, an in-depth analysis of H-89 vascular effects on both I Ca1.2 and contractility was undertaken by performing whole-cell patch-clamp recordings and functional experiments in rat tail main artery single myocytes and rings, respectively. H-89 inhibited I Ca1.2 with a pIC 50 (M) value of about 5.5, even under conditions where PKA activity was either abolished by both the PKA antagonists KT5720 and protein kinase inhibitor fragment 6-22 amide or enhanced by the PKA stimulators 6-Bnz-cAMP and 8-Br-cAMP. Inhibition of I Ca1.2 by H-89 appeared almost irreversible upon washout, was charge carrier- and voltage-dependent, and antagonised by the Ca v 1.2 channel agonist (S)-(-)-Bay K 8644. H-89 did not alter both potency and efficacy of verapamil, did not affect current kinetics or voltage-dependent activation, while shifting to the left the 50% voltage of inactivation in a concentration-dependent manner. H-89 docked at the α 1C subunit in a pocket region close to that of (S)-(-)-Bay K 8644 docking, forming a hydrogen bond with the same, key amino acid residue Tyr-1489. Finally, both high K + - and (S)-(-)-Bay K 8644-induced contractions of rings were fully reverted by H-89. In conclusion, these results indicate that H-89 inhibited vascular I Ca1.2 and, consequently, the contractile function through a PKA-independent mechanism. Therefore, caution is recommended when interpreting experiments where H-89 is used to inhibit vascular smooth muscle PKA. Copyright © 2017 Elsevier Inc. All rights reserved.

  14. Efficacy of a non-hypercalcemic vitamin-D2 derived anti-cancer agent (MT19c and inhibition of fatty acid synthesis in an ovarian cancer xenograft model.

    Directory of Open Access Journals (Sweden)

    Richard G Moore

    Full Text Available BACKGROUND: Numerous vitamin-D analogs exhibited poor response rates, high systemic toxicities and hypercalcemia in human trials to treat cancer. We identified the first non-hypercalcemic anti-cancer vitamin D analog MT19c by altering the A-ring of ergocalciferol. This study describes the therapeutic efficacy and mechanism of action of MT19c in both in vitro and in vivo models. METHODOLOGY/PRINCIPAL FINDING: Antitumor efficacy of MT19c was evaluated in ovarian cancer cell (SKOV-3 xenografts in nude mice and a syngenic rat ovarian cancer model. Serum calcium levels of MT19c or calcitriol treated animals were measured. In-silico molecular docking simulation and a cell based VDR reporter assay revealed MT19c-VDR interaction. Genomewide mRNA analysis of MT19c treated tumors identified drug targets which were verified by immunoblotting and microscopy. Quantification of cellular malonyl CoA was carried out by HPLC-MS. A binding study with PPAR-Y receptor was performed. MT19c reduced ovarian cancer growth in xenograft and syngeneic animal models without causing hypercalcemia or acute toxicity. MT19c is a weak vitamin-D receptor (VDR antagonist that disrupted the interaction between VDR and coactivator SRC2-3. Genome-wide mRNA analysis and western blot and microscopy of MT19c treated xenograft tumors showed inhibition of fatty acid synthase (FASN activity. MT19c reduced cellular levels of malonyl CoA in SKOV-3 cells and inhibited EGFR/phosphoinositol-3kinase (PI-3K activity independently of PPAR-gamma protein. SIGNIFICANCE: Antitumor effects of non-hypercalcemic agent MT19c provide a new approach to the design of vitamin-D based anticancer molecules and a rationale for developing MT19c as a therapeutic agent for malignant ovarian tumors by targeting oncogenic de novo lipogenesis.

  15. Melatonin Decreases Glucose Metabolism in Prostate Cancer Cells: A 13C Stable Isotope-Resolved Metabolomic Study.

    Science.gov (United States)

    Hevia, David; Gonzalez-Menendez, Pedro; Fernandez-Fernandez, Mario; Cueto, Sergio; Rodriguez-Gonzalez, Pablo; Garcia-Alonso, Jose I; Mayo, Juan C; Sainz, Rosa M

    2017-07-26

    The pineal neuroindole melatonin exerts an exceptional variety of systemic functions. Some of them are exerted through its specific membrane receptors type 1 and type 2 (MT1 and MT2) while others are mediated by receptor-independent mechanisms. A potential transport of melatonin through facilitative glucose transporters (GLUT/ SLC2A ) was proposed in prostate cancer cells. The prostate cells have a particular metabolism that changes during tumor progression. During the first steps of carcinogenesis, oxidative phosphorylation is reactivated while the switch to the "Warburg effect" only occurs in advanced tumors and in the metastatic stage. Here, we investigated whether melatonin might change prostate cancer cell metabolism. To do so, 13 C stable isotope-resolved metabolomics in androgen sensitive LNCaP and insensitive PC-3 prostate cancer cells were employed. In addition to metabolite 13 C-labeling, ATP/AMP levels, and lactate dehydrogenase or pentose phosphate pathway activity were measured. Melatonin reduces lactate labeling in androgen-sensitive cells and it also lowers 13 C-labeling of tricarboxylic acid cycle metabolites and ATP production. In addition, melatonin reduces lactate 13 C-labeling in androgen insensitive prostate cancer cells. Results demonstrated that melatonin limits glycolysis as well as the tricarboxylic acid cycle and pentose phosphate pathway in prostate cancer cells, suggesting that the reduction of glucose uptake is a major target of the indole in this tumor type.

  16. Melatonin Decreases Glucose Metabolism in Prostate Cancer Cells: A 13C Stable Isotope-Resolved Metabolomic Study

    Science.gov (United States)

    Hevia, David; Gonzalez-Menendez, Pedro; Fernandez-Fernandez, Mario; Cueto, Sergio; Mayo, Juan C.

    2017-01-01

    The pineal neuroindole melatonin exerts an exceptional variety of systemic functions. Some of them are exerted through its specific membrane receptors type 1 and type 2 (MT1 and MT2) while others are mediated by receptor-independent mechanisms. A potential transport of melatonin through facilitative glucose transporters (GLUT/SLC2A) was proposed in prostate cancer cells. The prostate cells have a particular metabolism that changes during tumor progression. During the first steps of carcinogenesis, oxidative phosphorylation is reactivated while the switch to the “Warburg effect” only occurs in advanced tumors and in the metastatic stage. Here, we investigated whether melatonin might change prostate cancer cell metabolism. To do so, 13C stable isotope-resolved metabolomics in androgen sensitive LNCaP and insensitive PC-3 prostate cancer cells were employed. In addition to metabolite 13C-labeling, ATP/AMP levels, and lactate dehydrogenase or pentose phosphate pathway activity were measured. Melatonin reduces lactate labeling in androgen-sensitive cells and it also lowers 13C-labeling of tricarboxylic acid cycle metabolites and ATP production. In addition, melatonin reduces lactate 13C-labeling in androgen insensitive prostate cancer cells. Results demonstrated that melatonin limits glycolysis as well as the tricarboxylic acid cycle and pentose phosphate pathway in prostate cancer cells, suggesting that the reduction of glucose uptake is a major target of the indole in this tumor type. PMID:28933733

  17. Comparison of [(11)C]Choline ([(11)C]CHO) and [(18)F]Bombesin (BAY 86-4367) as Imaging Probes for Prostate Cancer in a PC-3 Prostate Cancer Xenograft Model.

    Science.gov (United States)

    Schwarzenböck, Sarah Marie; Schmeja, Philipp; Kurth, Jens; Souvatzoglou, Michael; Nawroth, Roman; Treiber, Uwe; Kundt, Guenther; Berndt, Sandra; Graham, Keith; Senekowitsch-Schmidtke, Reingard; Schwaiger, Markus; Ziegler, Sibylle I; Dinkelborg, Ludger; Wester, Hans-Jürgen; Krause, Bernd Joachim

    2016-06-01

    Carbon-11- and fluorine-18-labeled choline derivatives are commonly used in prostate cancer imaging in the clinical setting for staging and re-staging of prostate cancer. Due to a limited detection rate of established positron emission tomography (PET) tracers, there is a clinical need for innovative tumor-specific PET compounds addressing new imaging targets. The aim of this study was to compare the properties of [(18)F]Bombesin (BAY 86-4367) as an innovative biomarker for prostate cancer imaging targeting the gastrin-releasing peptide receptor and [(11)C]Choline ([(11)C]CHO) in a human prostate tumor mouse xenograft model by small animal PET/X-ray computed tomography (CT). We carried out a dual-tracer small animal PET/CT study comparing [(18)F]Bombesin and [(11)C]CHO. The androgen-independent human prostate tumor cell line PC-3 was implanted subcutaneously in the flanks of nu/nu NMRI mice (n = 10) (PET/CT measurements of two [(11)C]Choline mice could not be analyzed due to technical reasons). [(18)F]Bombesin and [(11)C]CHO PET/CT imaging was performed about 3-4 weeks after the implantation of PC-3 cells on two separate days. After the intravenous tail vein injection of 14 MBq [(18)F]Bombesin and 37 MBq [(11)C]CHO, respectively, a dynamic study over 60 min was acquired in list mode using an Inveon animal PET/CT scanner (Siemens Medical Solutions). The sequence of [(18)F]Bombesin and [(11)C]CHO was randomized. Image analysis was performed using summed images as well as dynamic data. To calculate static and dynamic tumor-to-muscle (T/M), tumor-to-blood (T/B), liver-to-blood (L/B), and kidney-to-blood (K/B) ratios, 4 × 4 × 4 mm(3) volumes of interest (VOIs) of tumor, muscle (thigh), liver, kidney, and blood derived from transversal slices were used. The mean T/M ratio of [(18)F]Bombesin and [(11)C]CHO was 6.54 ± 2.49 and 1.35 ± 0.30, respectively. The mean T/B ratio was 1.83 ± 0.79 for [(18)F]Bombesin and 0.55 ± 0.10 for [(11)C

  18. No evidence for association of ataxia-telangiectasia mutated gene T2119C and C3161G amino acid substitution variants with risk of breast cancer

    International Nuclear Information System (INIS)

    Spurdle, Amanda B; Hopper, John L; Chen, Xiaoqing; McCredie, Margaret RE; Giles, Graham G; Newman, Beth; Chenevix-Trench, Georgia; Khanna, KumKum

    2002-01-01

    There is evidence that certain mutations in the double-strand break repair pathway ataxia-telangiectasia mutated gene act in a dominant-negative manner to increase the risk of breast cancer. There are also some reports to suggest that the amino acid substitution variants T2119C Ser707Pro and C3161G Pro1054Arg may be associated with breast cancer risk. We investigate the breast cancer risk associated with these two nonconservative amino acid substitution variants using a large Australian population-based case–control study. The polymorphisms were genotyped in more than 1300 cases and 600 controls using 5' exonuclease assays. Case–control analyses and genotype distributions were compared by logistic regression. The 2119C variant was rare, occurring at frequencies of 1.4 and 1.3% in cases and controls, respectively (P = 0.8). There was no difference in genotype distribution between cases and controls (P = 0.8), and the TC genotype was not associated with increased risk of breast cancer (adjusted odds ratio = 1.08, 95% confidence interval = 0.59–1.97, P = 0.8). Similarly, the 3161G variant was no more common in cases than in controls (2.9% versus 2.2%, P = 0.2), there was no difference in genotype distribution between cases and controls (P = 0.1), and the CG genotype was not associated with an increased risk of breast cancer (adjusted odds ratio = 1.30, 95% confidence interval = 0.85–1.98, P = 0.2). This lack of evidence for an association persisted within groups defined by the family history of breast cancer or by age. The 2119C and 3161G amino acid substitution variants are not associated with moderate or high risks of breast cancer in Australian women

  19. Frequency of the CHEK2 1100delC mutation among women with breast cancer: an international study.

    Science.gov (United States)

    Zhang, Shiyu; Phelan, Catherine M; Zhang, Phil; Rousseau, Francois; Ghadirian, Parviz; Robidoux, Andre; Foulkes, William; Hamel, Nancy; McCready, David; Trudeau, Maureen; Lynch, Henry; Horsman, Douglas; De Matsuda, Maria Lourdes Leon; Aziz, Zeba; Gomes, Magda; Costa, Mauricio Magalhaes; Liede, Alexander; Poll, Aletta; Sun, Ping; Narod, Steven A

    2008-04-01

    A founder allele in the CHEK2 gene (1100delC) has been associated with an elevated risk of breast cancer. This allele is responsible for the majority of CHEK2-associated breast cancers in women from northern European countries; however, within Europe, it seems to be rare in countries that are close to the Mediterranean. The frequency of the 1100delC allele has not been measured in non-White populations. We measured the frequency of the CHEK2 founder allele in 3,882 breast cancer patients and 8,609 controls from various countries. The allele was not seen among Asian patients (from Pakistan or the Philippines) and was present in 1 of 155 cases from Brazil. Among White women, the allele was present in 1.5% of 825 familial cases of breast cancer and in 0.7% of 1,106 patients with nonfamilial breast cancer. The allele was equally frequent in Jewish and non-Jewish patients. We estimate that the CHEK2 1100delC allele is associated with an odds ratio of 2.6 for breast cancer, which corresponds to a lifetime risk of approximately 24% in Ontario.

  20. Optimized anion exchange column isolation of zirconium-89 (89Zr) from yttrium cyclotron target: Method development and implementation on an automated fluidic platform.

    Science.gov (United States)

    O'Hara, Matthew J; Murray, Nathaniel J; Carter, Jennifer C; Morrison, Samuel S

    2018-04-13

    Zirconium-89 ( 89 Zr), produced by the (p, n) reaction from naturally monoisotopic yttrium ( nat Y), is a promising positron emitting isotope for immunoPET imaging. Its long half-life of 78.4 h is sufficient for evaluating slow physiological processes. A prototype automated fluidic system, coupled to on-line and in-line detectors, has been constructed to facilitate development of new 89 Zr purification methodologies. The highly reproducible reagent delivery platform and near-real time monitoring of column effluents allows for efficient method optimization. The separation of Zr from dissolved Y metal targets was evaluated using several anion exchange resins. Each resin was evaluated against its ability to quantitatively capture Zr from a load solution high in dissolved Y. The most appropriate anion exchange resin for this application was identified, and the separation method was optimized. The method is capable of a high Y decontamination factor (>10 5 ) and has been shown to remove Fe, an abundant contaminant in Y foils, from the 89 Zr elution fraction. Finally, the method was evaluated using cyclotron bombarded Y foil targets; the method was shown to achieve >95% recovery of the 89 Zr present in the foils. The anion exchange column method described here is intended to be the first 89 Zr isolation stage in a dual-column purification process. Copyright © 2018 Elsevier B.V. All rights reserved.

  1. An in vivo C. elegans model system for screening EGFR-inhibiting anti-cancer drugs.

    Directory of Open Access Journals (Sweden)

    Young-Ki Bae

    Full Text Available The epidermal growth factor receptor (EGFR is a well-established target for cancer treatment. EGFR tyrosine kinase (TK inhibitors, such as gefinitib and erlotinib, have been developed as anti-cancer drugs. Although non-small cell lung carcinoma with an activating EGFR mutation, L858R, responds well to gefinitib and erlotinib, tumors with a doubly mutated EGFR, T790M-L858R, acquire resistance to these drugs. The C. elegans EGFR homolog LET-23 and its downstream signaling pathway have been studied extensively to provide insight into regulatory mechanisms conserved from C. elegans to humans. To develop an in vivo screening system for potential cancer drugs targeting specific EGFR mutants, we expressed three LET-23 chimeras in which the TK domain was replaced with either the human wild-type TK domain (LET-23::hEGFR-TK, a TK domain with the L858R mutation (LET-23::hEGFR-TK[L858R], or a TK domain with the T790M-L858R mutations (LET-23::hEGFR-TK[T790M-L858R] in C. elegans vulval cells using the let-23 promoter. The wild-type hEGFR-TK chimeric protein rescued the let-23 mutant phenotype, and the activating mutant hEGFR-TK chimeras induced a multivulva (Muv phenotype in a wild-type C. elegans background. The anti-cancer drugs gefitinib and erlotinib suppressed the Muv phenotype in LET-23::hEGFR-TK[L858R]-expressing transgenic animals, but not in LET-23::hEGFR-TK[T790M-L858R] transgenic animals. As a pilot screen, 8,960 small chemicals were tested for Muv suppression, and AG1478 (an EGFR-TK inhibitor and U0126 (a MEK inhibitor were identified as potential inhibitors of EGFR-mediated biological function. In conclusion, transgenic C. elegans expressing chimeric LET-23::hEGFR-TK proteins are a model system that can be used in mutation-specific screens for new anti-cancer drugs.

  2. Role of DNA methylation in miR-200c/141 cluster silencing in invasive breast cancer cells

    Directory of Open Access Journals (Sweden)

    Wernet Peter

    2010-08-01

    Full Text Available Abstract Background The miR-200c/141 cluster has recently been implicated in the epithelial to mesenchymal transition (EMT process. The expression of these two miRNAs is inversely correlated with tumorigenicity and invasiveness in several human cancers. The role of these miRNAs in cancer progression is based in part on their capacity to target the EMT activators ZEB1 and ZEB2, two transcription factors, which in turn repress expression of E-cadherin. Little is known about the regulation of the mir200c/141 cluster, whose targeting has been proposed as a promising new therapy for the most aggressive tumors. Findings We show that the miR-200c/141 cluster is repressed by DNA methylation of a CpG island located in the promoter region of these miRNAs. Whereas in vitro methylation of the miR-200c/141 promoter led to shutdown of promoter activity, treatment with a demethylating agent caused transcriptional reactivation in breast cancer cells formerly lacking expression of miR-200c and miR-141. More importantly, we observed that DNA methylation of the identified miR-200c/141 promoter was tightly correlated with phenotype and the invasive capacity in a panel of 8 human breast cancer cell lines. In line with this, in vitro induction of EMT by ectopic expression of the EMT transcription factor Twist in human immortalized mammary epithelial cells (HMLE was accompanied by increased DNA methylation and concomitant repression of the miR-200c/141 locus. Conclusions The present study demonstrates that expression of the miR-200c/141 cluster is regulated by DNA methylation, suggesting epigenetic regulation of this miRNA locus in aggressive breast cancer cell lines as well as untransformed mammary epithelial cells. This epigenetic silencing mechanism might represent a novel component of the regulatory circuit for the maintenance of EMT programs in cancer and normal cells.

  3. Role of DNA methylation in miR-200c/141 cluster silencing in invasive breast cancer cells.

    Science.gov (United States)

    Neves, Rui; Scheel, Christina; Weinhold, Sandra; Honisch, Ellen; Iwaniuk, Katharina M; Trompeter, Hans-Ingo; Niederacher, Dieter; Wernet, Peter; Santourlidis, Simeon; Uhrberg, Markus

    2010-08-03

    The miR-200c/141 cluster has recently been implicated in the epithelial to mesenchymal transition (EMT) process. The expression of these two miRNAs is inversely correlated with tumorigenicity and invasiveness in several human cancers. The role of these miRNAs in cancer progression is based in part on their capacity to target the EMT activators ZEB1 and ZEB2, two transcription factors, which in turn repress expression of E-cadherin. Little is known about the regulation of the mir200c/141 cluster, whose targeting has been proposed as a promising new therapy for the most aggressive tumors. We show that the miR-200c/141 cluster is repressed by DNA methylation of a CpG island located in the promoter region of these miRNAs. Whereas in vitro methylation of the miR-200c/141 promoter led to shutdown of promoter activity, treatment with a demethylating agent caused transcriptional reactivation in breast cancer cells formerly lacking expression of miR-200c and miR-141. More importantly, we observed that DNA methylation of the identified miR-200c/141 promoter was tightly correlated with phenotype and the invasive capacity in a panel of 8 human breast cancer cell lines. In line with this, in vitro induction of EMT by ectopic expression of the EMT transcription factor Twist in human immortalized mammary epithelial cells (HMLE) was accompanied by increased DNA methylation and concomitant repression of the miR-200c/141 locus. The present study demonstrates that expression of the miR-200c/141 cluster is regulated by DNA methylation, suggesting epigenetic regulation of this miRNA locus in aggressive breast cancer cell lines as well as untransformed mammary epithelial cells. This epigenetic silencing mechanism might represent a novel component of the regulatory circuit for the maintenance of EMT programs in cancer and normal cells.

  4. Classification of Dukes' B and C colorectal cancers using expression arrays

    DEFF Research Database (Denmark)

    Frederiksen, C.M.; Knudsen, Steen; Laurberg, S.

    2003-01-01

    Purpose. Colorectal cancer is one of the most common malignancies. Substaging of the cancer is of importance not only to prognosis but also to treatment. Classification of substages based on DNA microarray technology is currently the most promising approach. We therefore investigated if gene...... expression microarrays could be used to classify colorectal tumors. Methods. We used the Affymetrix oligonucleotide arrays to analyze the expression of more than 5,000 genes in samples from the sigmoid and upper rectum of the left colon. Five samples were from normal mucosa and five samples from each...... expression of one of the most common malignancies, colorectal cancer, now seems to be within reach. The data indicates that it is possible at least to classify Dukes' B and C colorectal tumors with microarrays....

  5. SU-E-I-82: PET Radiopharmaceuticals for Prostate Cancer Imaging: A Review

    International Nuclear Information System (INIS)

    Fernandes, F; Silva, D da; Rodrigues, L

    2015-01-01

    Purpose: The aim of this work was to review new and clinical practice PET radiopharmaceuticals for prostate cancer imaging. Methods: PET radiopharmaceuticals were reviewed on the main databases. Availability, dosimetry, accuracy and limitations were considered. Results: The following radioisotopes with respective physical half-life and mean positron energy were found: 18 F (109,7 min, 249,8 keV), 89 Zr (78,4 hs, 395,5 keV), 11 C (20,4 min, 385,7 keV) and 68 Ga (67,8 min, 836 keV). 68 Ga was the only one not produced by cyclotron. Radiopharmaceuticals uptake by glucose metabolism ( 18 F-FDG), lipogenesis ( 11 C-Choline and 11 C-Acetate), amino acid transport (Anti- 18 F-FACBC), bone matrix ( 18 F-NaF), prostatespecific membrane antigen ( 68 Ga-PSMA and 89 Zr-J591), CXCR receptors ( 89 Ga-Pentixafor), adrenal receptors ( 18 F-FDHT) and gastrin release peptide receptor (bombesin analogue). Most of radiopharmaceuticals are urinary excretion, so bladder is the critical organ. 11C-choline (pancreas), Anti- 18 FFACBC (liver) and 18 F-FBDC (stomach wall) are the exception. Higher effective dose was seen 18 F-NaF (27 μSv/MBq) while the lowest was 11 CAcetate (3,5 μSv/MBq). Conclusion: Even though 18 F-FDG has a large availability its high urinary excretion and poor uptake to slow growing disease offers weak results for prostate cancer. Better accuracy is obtained when 18 F-NaF is used for bone metastatic investigation although physicians tend to choose bone scintigraphy probably due to its cost and practice. Many guidelines in oncology consider 11 C or 18 F labeled with Choline the gold standard for biochemical relapse after radical treatment. Local, lymph node and distant metastatic relapse can be evaluated at same time with this radiopharmaceutical. There is no consensus over bigger urinary excretion for 18 F labeling. Anti- 18 F-FACBC, 68 Ga-PSMA and 68 Ga-Pentixafor are demonstrating good results but more researches are needed. While PSMA imaging seems to be

  6. Building a Latin American cancer patient advocacy movement: Latin American cancer NGO regional overview Desarrollando un movimiento de apoyo para pacientes de cáncer en America Latina: resumen regional - ONGs de cáncer

    Directory of Open Access Journals (Sweden)

    Alessandra Durstine

    2009-01-01

    Full Text Available The objective of the this paper is to assess and identify the key strengths and weaknesses for cancer control NGOs in Latin America, with the goal to make recommendations about how to improve thev impact of the patient advocacy movement as it pertains to cancer. The methods included literature review, expert interviews and site visits to Latin American cancer hospitals and NGOs. The overall findings conclude that NGOs currently do not take a leadership role in cancer control in Latin America. The lack of a survivorship movement, faulty patient information services and failure of the governments to include NGOs in policy creation are identified as areas for further project work and collaboration. The stigma of cancer still remains and a burgeoning patient movement can be created to help destigmatize and debunk the myths that surround cancer.El objetivo de este artículo es el de identificar y evaluar las fortalezas y debilidades clave de las ONG dedicadas al control del cáncer en Latinoamérica, con el fin de generar recomendaciones sobre el modo de mejorar el impacto del movimiento de apoyo para pacientes de cáncer. Los métodos incluyeron una revisión de la literatura, entrevistas a expertos y visitas a hospiptales y ONG dedicados al cáncer en Latinoamérica. Los hallazgos principales permiten concluir que en este momento las ONG no tienen un rol de liderazgo para el control del cáncer en Latinoamérica. La ausencia de un movimiento de sobrevivientes, servicios de información deficientes a los pacientes y el fracaso del gobierno para incluir a las ONG en la creación de políticas se identifican como áreas de trabajo y colaboración en proyectos a futuro. El estigma del cáncer aún subsiste y es factible crear un movimiento que florezca y ayude a desvanecerlo al exponer los mitos que rodean este padecimiento.

  7. Reliability and Validity of the Korean Version of the Cancer Stigma Scale.

    Science.gov (United States)

    So, Hyang Sook; Chae, Myeong Jeong; Kim, Hye Young

    2017-02-01

    In this study the reliability and validity of the Korean version of the Cancer Stigma Scale (KCSS) was evaluated. The KCSS was formed through translation and modification of Cataldo Lung Cancer Stigma Scale. The KCSS, Psychological Symptom Inventory (PSI), and European Organization for Research and Treatment of Cancer Quality of Life Questionnaire - Core 30 (EORTC QLQ-C30) were administered to 247 men and women diagnosed with one of the five major cancers. Construct validity, item convergent and discriminant validity, concurrent validity, known-group validity, and internal consistency reliability of the KCSS were evaluated. Exploratory factor analysis supported the construct validity with a six-factor solution; that explained 65.7% of the total variance. The six-factor model was validated by confirmatory factor analysis (Q (χ²/df)= 2.28, GFI=.84, AGFI=.81, NFI=.80, TLI=.86, RMR=.03, and RMSEA=.07). Concurrent validity was demonstrated with the QLQ-C30 (global: r=-.44; functional: r=-.19; symptom: r=.42). The KCSS had known-group validity. Cronbach's alpha coefficient for the 24 items was .89. The results of this study suggest that the 24-item KCSS has relatively acceptable reliability and validity and can be used in clinical research to assess cancer stigma and its impacts on health-related quality of life in Korean cancer patients. © 2017 Korean Society of Nursing Science

  8. Simultaneous hyperpolarized 13C-pyruvate MRI and 18F-FDG-PET in cancer (hyperPET)

    DEFF Research Database (Denmark)

    Gutte, Henrik; Hansen, Adam E.; Henriksen, Sarah T.

    2015-01-01

    named this concept hyper PET. Intravenous injection of the hyperpolarized 13C-pyruvate results in an increase of 13C-lactate, 13C-alanine and 13CCO2 (13C-HCO3) resonance peaks relative to the tissue, disease and the metabolic state probed. Accordingly, with dynamic nuclear polarization (DNP) and use......In this paper we demonstrate, for the first time, the feasibility of a new imaging concept - combined hyperpolarized 13C-pyruvate magnetic resonance spectroscopic imaging (MRSI) and 18F-FDG-PET imaging. This procedure was performed in a clinical PET/MRI scanner with a canine cancer patient. We have...... of 13C-pyruvate it is now possible to directly study the Warburg Effect through the rate of conversion of 13C-pyruvate to 13C-lactate. In this study, we combined it with 18F-FDG-PET that studies uptake of glucose in the cells. A canine cancer patient with a histology verified local recurrence...

  9. Betulin induces cytochrome c release and apoptosis in colon cancer cells via NOXA.

    Science.gov (United States)

    Zhou, Zhiyuan; Zhu, Chenfang; Cai, Zhongfang; Zhao, Feng; He, Liu; Lou, Xiaolou; Qi, Xiaoliang

    2018-05-01

    Betulin is a common triterpene that can be readily obtained from various plants, particularly birch trees, in their natural environment. Specific tumor cells are sensitive to betulin, whereas healthy cells are not. Betulin was observed to stimulate programmed cell death of various cancer cell lines; however, the precise molecular mechanism of action of betulin remains unknown. The present study used colon cancer cells, in which mass apoptosis triggered by betulin was identified, and the apoptotic process was demonstrated to occur via the activation of caspase-3 and -9 pathways. In addition, release of cytochrome c was detected. Furthermore, the pro-apoptotic member of the Bcl-2 protein family, NOXA, was induced following treatment with betulin, and the downregulation of NOXA markedly suppressed the release of cytochrome c and apoptosis in colon cancer cells. Conversely, the overexpression of NOXA further enhanced betulin-induced apoptosis. The present study therefore offers novel insights into the mechanism of action of the natural compound betulin against tumors.

  10. Study of the proton momentum spectrum from deuteron fragmentation at 8.9 GeV/c and an estimate of admixture parameters for the six-quark state in deuteron

    International Nuclear Information System (INIS)

    Ableev, V.G.; Abdushukurov, D.A.; Avramenko, S.A.

    1982-01-01

    Using a magnetic spectrometer with proportional chambers and Cherenkov counters, the momentum spectrum of protons emitted at angles below O.4 deg in the stripping reaction d+ 12 C → p+X has been measured at a deuteron momentum of 8.9 GeV/c for the proton momentum in the range of 3.56 GeV/c <= p <8.05 GeV/c (-206 MeV/c <= p*sub(parallel) <= 580 MeV/c in the deuteron rest system). From the analysis of the invariant cross sections the estimates of parameters of six-quark state admixture in a deuteron are obtained: the admixture-(3.1+-0.2)%, the average square radius of the six-cquark state-(0.87-0.10) Fm, a relative phase of two-nucleon and six-quark components-(61 deg +- 11 deg) for the two-nucleon Reid wave function with a soft core, respectively, =(4.3+-0.4)%, (0.95+-0.05) lm and (82 deg +- 6 deg) for the Paris potential wave function. In the proton momentum region of 296 MeV/c < p*sub(parallel) <= 378 MeV/c a peculiarity in the spectrum has been observed corresponding kinematically to the production of a dibaryon resonance with a mass ranging from 2.0 to 2.2 GeV

  11. Lymphangiogenesis in cervical cancer evaluated by expression of the VEGF-C gene in clinical stage IB-IIIB

    Directory of Open Access Journals (Sweden)

    Magdalena Franc

    2015-02-01

    Full Text Available Introduction : The aim of the present study was to evaluate the profile of VEGF-C gene expression in particular stages of cervical cancer (IB-IIIB and to estimate the correlation between VEGF-C mRNA quantity profile and clinical stage. Material and methods : Material for molecular analysis consisted of cervical cancer tissue specimens collected from 38 women (10, 15, 13 cases were classified as IB, IIB and IIIB, respectively. The control group was composed of normal cervical tissues collected from 10 women who underwent hysterectomy for non-oncological reasons. The number of VEGF-C mRNA copies in particular groups was estimated by the reverse transcription quantitative polymerase chain reaction (RT-qPCR method. Results: In the control group the average number of mRNA copies was 134 ± 36 (median: 106, in a group with stage IB it was 16 077 ± 7090 (median: 580, for stage IIB – 35 019 ± 8945 (median: 40 870. The highest number of mRNA VEGF-C copies was derived in a group of patients with cervical cancer of stage IIIB. The average quantity was 56 155 ± 12 470, whereas median 55 981. A statistically significantly higher level of VEGF-C gene expression was disclosed in cervical cancer specimens with stage IIB and IIIB than in the control group. In stage IIIB, the VEGF-C gene expression was significantly higher than in specimens derived from individuals in stage IB. Conclusions : In squamous cell carcinoma of the uterine cervix of stage IB-IIIB genes involved in lymphangio­genesis, especially VEGF-C , are expressed, which expression increases as the clinical stage of cervical cancer is higher.

  12. Preliminary study of p53 and c-erbB-2 expression in gallbladder cancer in Indian patients

    Directory of Open Access Journals (Sweden)

    Singh Usha

    2006-05-01

    Full Text Available Abstract Background The inactivation of the tumour suppressor gene and activation of the proto-oncogene are the key steps in the development of the human cancer. The p53 and c-erbB-2 are the best examples of it. In the present study, our aim was to determine the role of these genes in the carcinogenesis of gallbladder by immunohistochemistry. Methods In all 78 consecutive patients of gall bladder diseases were studied for p53 and c-erbB-2 expression immunohistochemically and their expression was correlated with the age, grades and stages of the disease and presence of stone. An informed consent was obtained in each case. Chi square and z test were applied to see the association of p53 and c-erbB-2 over expression with other clinicopathological factors. Results Eight (20% patients of gall bladder cancer were positive for p53 expression and 10 (25% patients for c-erbB-2. The p53 positivity increased with increasing grade while cerbB-2 positivity decreased with increasing grade of gall bladder cancer. Mean age in cerbB-2 positive cases were lesser as compared to negative cases while p53 did not show such association with age. Conclusion Only one case of gall bladder cancer co-expressed the p53 and c-erbB-2, thereby suggesting that p53 and c-erbB-2 may have independent role in carcinogenesis of gall bladder cancer. c-erbB-2 over expression in adenoma and younger age group indicates its role as an early event in carcinogenesis of gallbladder. However study of larger sample is required to further validate the results.

  13. Elevated levels of the complement activation product C4d in bronchial fluids for the diagnosis of lung cancer.

    Directory of Open Access Journals (Sweden)

    Daniel Ajona

    Full Text Available Molecular markers in bronchial fluids may contribute to the diagnosis of lung cancer. We previously observed a significant increase of C4d-containing complement degradation fragments in bronchoalveolar lavage (BAL supernatants from lung cancer patients in a cohort of 50 cases and 22 controls (CUN cohort. The present study was designed to determine the diagnostic performance of these complement fragments (hereinafter jointly referred as C4d in bronchial fluids. C4d levels were determined in BAL supernatants from two independent cohorts: the CU cohort (25 cases and 26 controls and the HUVR cohort (60 cases and 98 controls. A series of spontaneous sputum samples from 68 patients with lung cancer and 10 controls was also used (LCCCIO cohort. Total protein content, complement C4, complement C5a, and CYFRA 21-1 were also measured in all cohorts. C4d levels were significantly increased in BAL samples from lung cancer patients. The area under the ROC curve was 0.82 (95%CI = 0.71-0.94 and 0.67 (95%CI = 0.58-0.76 for the CU and HUVR cohorts, respectively. In addition, unlike the other markers, C4d levels in BAL samples were highly consistent across the CUN, CU and HUVR cohorts. Interestingly, C4d test markedly increased the sensitivity of bronchoscopy in the two cohorts in which cytological data were available (CUN and HUVR cohorts. Finally, in the LCCCIO cohort, C4d levels were higher in sputum supernatants from patients with lung cancer (area under the ROC curve: 0.7; 95%CI = 0.56-0.83. In conclusion, C4d is consistently elevated in bronchial fluids from lung cancer patients and may be used to improve the diagnosis of the disease.

  14. 40 CFR 89.902 - Definitions.

    Science.gov (United States)

    2010-07-01

    ... piece of equipment employed from year to year in the ordinary course of business for product development, production method assessment, and market promotion purposes. Testing exemption means an exemption which may be granted under § 89.1004(b) for the purpose of research investigations, studies, demonstrations or...

  15. 89Zr-Oxine Complex PET Cell Imaging in Monitoring Cell-based Therapies

    Science.gov (United States)

    Wu, Haitao; Asiedu, Kingsley O.; Szajek, Lawrence P.; Griffiths, Gary L.; Choyke, Peter L.

    2015-01-01

    Purpose To develop a clinically translatable method of cell labeling with zirconium 89 (89Zr) and oxine to track cells with positron emission tomography (PET) in mouse models of cell-based therapy. Materials and Methods This study was approved by the institutional animal care committee. 89Zr-oxine complex was synthesized in an aqueous solution. Cell labeling conditions were optimized by using EL4 mouse lymphoma cells, and labeling efficiency was examined by using dendritic cells (DCs) (n = 4), naïve (n = 3) and activated (n = 3) cytotoxic T cells (CTLs), and natural killer (NK) (n = 4), bone marrow (n = 4), and EL4 (n = 4) cells. The effect of 89Zr labeling on cell survival, proliferation, and function were evaluated by using DCs (n = 3) and CTLs (n = 3). Labeled DCs (444–555 kBq/[5 × 106] cells, n = 5) and CTLs (185 kBq/[5 × 106] cells, n = 3) transferred to mice were tracked with microPET/CT. In a melanoma immunotherapy model, tumor targeting and cytotoxic function of labeled CTLs were evaluated with imaging (248.5 kBq/[7.7 × 106] cells, n = 4) and by measuring the tumor size (n = 6). Two-way analysis of variance was used to compare labeling conditions, the Wilcoxon test was used to assess cell survival and proliferation, and Holm-Sidak multiple tests were used to assess tumor growth and perform biodistribution analyses. Results 89Zr-oxine complex was synthesized at a mean yield of 97.3% ± 2.8 (standard deviation). It readily labeled cells at room temperature or 4°C in phosphate-buffered saline (labeling efficiency range, 13.0%–43.9%) and was stably retained (83.5% ± 1.8 retention on day 5 in DCs). Labeling did not affect the viability of DCs and CTLs when compared with nonlabeled control mice (P > .05), nor did it affect functionality. 89Zr-oxine complex enabled extended cell tracking for 7 days. Labeled tumor-specific CTLs accumulated in the tumor (4.6% on day 7) and induced tumor regression (P cell tracking technique for use with PET that is

  16. (89)Zr-Oxine Complex PET Cell Imaging in Monitoring Cell-based Therapies.

    Science.gov (United States)

    Sato, Noriko; Wu, Haitao; Asiedu, Kingsley O; Szajek, Lawrence P; Griffiths, Gary L; Choyke, Peter L

    2015-05-01

    To develop a clinically translatable method of cell labeling with zirconium 89 ((89)Zr) and oxine to track cells with positron emission tomography (PET) in mouse models of cell-based therapy. This study was approved by the institutional animal care committee. (89)Zr-oxine complex was synthesized in an aqueous solution. Cell labeling conditions were optimized by using EL4 mouse lymphoma cells, and labeling efficiency was examined by using dendritic cells (DCs) (n = 4), naïve (n = 3) and activated (n = 3) cytotoxic T cells (CTLs), and natural killer (NK) (n = 4), bone marrow (n = 4), and EL4 (n = 4) cells. The effect of (89)Zr labeling on cell survival, proliferation, and function were evaluated by using DCs (n = 3) and CTLs (n = 3). Labeled DCs (444-555 kBq/[5 × 10(6)] cells, n = 5) and CTLs (185 kBq/[5 × 10(6)] cells, n = 3) transferred to mice were tracked with microPET/CT. In a melanoma immunotherapy model, tumor targeting and cytotoxic function of labeled CTLs were evaluated with imaging (248.5 kBq/[7.7 × 10(6)] cells, n = 4) and by measuring the tumor size (n = 6). Two-way analysis of variance was used to compare labeling conditions, the Wilcoxon test was used to assess cell survival and proliferation, and Holm-Sidak multiple tests were used to assess tumor growth and perform biodistribution analyses. (89)Zr-oxine complex was synthesized at a mean yield of 97.3% ± 2.8 (standard deviation). It readily labeled cells at room temperature or 4°C in phosphate-buffered saline (labeling efficiency range, 13.0%-43.9%) and was stably retained (83.5% ± 1.8 retention on day 5 in DCs). Labeling did not affect the viability of DCs and CTLs when compared with nonlabeled control mice (P > .05), nor did it affect functionality. (89)Zr-oxine complex enabled extended cell tracking for 7 days. Labeled tumor-specific CTLs accumulated in the tumor (4.6% on day 7) and induced tumor regression (P cell tracking technique for use with PET that is applicable to a broad range of

  17. Diferenciais regionais de mortalidade por câncer no Estado do Rio de Janeiro, Brasil, 1979-1981 Regional differentials in cancer mortality in a region of, Brazil, 1979-1981

    Directory of Open Access Journals (Sweden)

    Cynthia Boschi

    1991-08-01

    Full Text Available A partir do fato de que os neoplasmas malignos foram a terceira causa de morte no Estado do Rio de Janeiro, Brasil, no ano de 1980, apresentando taxa bruta igual a 89,8 por 100.000 habitantes, foi analisada a mortalidade por câncer segundo suas principais localizações anatômicas, no período 1979-1981. Dividiu-se o Estado em três regiões distintas: Capital, Cinturão Metropolitano e Interior. Foram calculados coeficientes de mortalidade trienais, posteriormente padronizados pelo método direto utilizando-se, para tal, a população mundial. Para cumprir o objetivo de comparar diferentes regiões geográficas foram calculadas razões padronizadas de mortalidade. Observou-se que as principais localizações anatômicas foram pulmão, estômago, próstata, esôfago e fígado, nos homens; e mama, estômago, pulmão, cérvix uterino e útero (não especificado, nas mulheres. Encontrou-se que as maiores taxas para o total de tumores ocorreram na Capital e as menores no Interior, sendo as maiores razões padronizadas de mortalidade aquelas para mama (1,88, cólon (1,71 e pulmão (1,70. A mortalidade por neoplasmas malignos de esôfago e de fígado foi maior no Interior do que nas demais regiões, em ambos os sexos. Concluiu-se que existe comportamento distinto da mortalidade por câncer entre as diferentes regiões, apontando, mais uma vez, na direção da determinação ambiental de grande parte dos neoplasmas malignos.In 1980, malignant neoplasms ranked 3rd as a cause of death in the State of Rio de Janeiro, Brazil, with a crude mortality rate of 89.8 per 100,000. Cancer mortality data for 1979-1981 are presented for the State, with the objective of analyzing regional differentials. For the purpose of comparing mortality from the most important cancers, the State was divided into three regions: Capital, Metropolitan Belt and Interior, on the basis of the geographical structure of the State - which gave rise to the present urbanization patterns

  18. Both high expression of pyruvate kinase M2 and vascular endothelial growth factor-C predicts poorer prognosis in human breast cancer.

    Science.gov (United States)

    Lin, Yang; Liu, Fangfang; Fan, Yu; Qian, Xiaolong; Lang, Ronggang; Gu, Feng; Gu, Jun; Fu, Li

    2015-01-01

    Pyruvate kinase M2 (PKM2) and vascular endothelial growth factor-C (VEGF-C) have been known to play an important role in tumorigenesis and tumor progression in breast cancer. However, the association between PKM2 and VEGF-C in breast cancer remains unclear. In the present study, a total of 218 specimens from breast cancer patients and 26 paired breast tumors with adjacent normal tissues as well as two breast cancer cell lines were enrolled to investigate the correlation between PKM2 and VEGF-C. We found that PKM2 and VEGF-C mRNA levels were both significantly increasing in breast tumors compared with adjacent normal tissues. Knockdown of PKM2 mRNA expression resulted in VEGF-C mRNA and protein down-regulated as well as cell proliferation inhibited. A positive correlation between PKM2 and VEGF-C expression was identified by immunohistochemical analyses of 218 specimens of patients with breast cancer (P=0.023). PKM2 high expression was significantly correlated with histological grade (P=0.030), lymph node stage (P=0.001), besides VEGF-C high expression was significantly associated with lymphovascular invasion (P=0.012). While combined high expression of PKM2 and VEGF-C was found to be associated with worse histological grade, more lymph node metastasis, more lymphovascular invasion, shorter progression free survival (PFS), and poorer overall survival (OS) in human breast cancer. The results of the present study suggested that PKM2 expression was correlated with VEGF-C expression, and combination of PKM2 and VEGF-C levels had the better prognostic significance in predicting the poor outcome of patients with breast cancer.

  19. Transcriptional regulation of miR-146b by C/EBPβ LAP2 in esophageal cancer cells

    International Nuclear Information System (INIS)

    Li, Junxia; Shan, Fabo; Xiong, Gang; Wang, Ju-Ming; Wang, Wen-Lin; Xu, Xueqing; Bai, Yun

    2014-01-01

    Highlights: • MiR-146b promotes esophageal cancer cell proliferation. • MiR-146b inhibits esophageal cancer cell apoptosis. • C/EBPβ directly binds to miR-146b promoter conserved region. • MiR-146b is up-regulated by C/EBPβ LAP2 transcriptional activation. - Abstract: Recent clinical study indicated that up-regulation of miR-146b was associated with poor overall survival of patients in esophageal squamous cell carcinoma. However, the underlying mechanism of miR-146b dysregulation remains to be explored. Here we report that miR-146b promotes cell proliferation and inhibits cell apoptosis in esophageal cancer cell lines. Mechanismly, two C/EBPβ binding motifs are located in the miR-146b promoter conserved region. Among the three isoforms of C/EBPβ, C/EBPβ LAP2 positively regulated miR-146b expression and increases miR-146b levels in a dose-dependent manner through transcription activation of miR-146b gene. Together, these results suggest a miR-146b regulatory mechanism involving C/EBPβ, which may contribute to the up-regulation of miR-146b in esophageal squamous cell carcinoma

  20. Differential action on cancer and normal tissue by adrenochrome monoaminoguanidine methanesulfonate and cytochrome C combined with radiotherapy

    International Nuclear Information System (INIS)

    Nakatsugawa, S.; Sugahara, T.

    1994-01-01

    The possibility that radioprotective effects on potent natural killer (NK) cells by adrenochrome monoaminoguanidine methanesulfonate (AMM) + cytochrome C during radiotherapy (RT) for lung cancer might result in the radiosensitization of human lung cancer cells in vivo is examined. Human lung cancer xenografts in the right hind legs of KSN mice (10 weeks old) were locally irradiated with 20 Gy of X ray. AMM (10 mg/kg/day) and/or cytochrome C (CCC) (5 mg/kg/day) were given intraperitoneally immediately before or after RT, followed by daily administration for 4 days. Natural killer activities of host splenocytes were also tested with the standard 51 Cr releasing assay with YAC-1 cells as target cells. In a clinical study, 65 patients with lung cancer were treated with more than 50 Gy of RT with or without combination with AMM + CCC, OK-432 or AMM + CCC + OK-432. Before and after RT, lymphocyte subsets in the peripheral blood were examined with dichromatic analysis using an Ortho Spectrum IIIFCM system and fluorescent MABs. In this study, the change in the absolute number of each subset was investigated. AMM + cytochrome C augumented NK activity in KSN nude mice, protected potent NK cells in patients with lung cancer against RT and sensitized the human lung cancer xenografts to RT. AMM + cytochrome C may have potential as a differential modulator of radiosensitivity of normal tissues and of tumors. 8 refs., 2 figs., 1 tab

  1. Relative Apoptosis-inducing Potential of Homeopa-thic Condurango 6C and 30C in H460 Lung Cancer Cells In vitro

    Directory of Open Access Journals (Sweden)

    Sikdar Sourav

    2014-03-01

    Full Text Available Objectives: In homeopathy, it is claimed that more homeopathically-diluted potencies render more protective/curative effects against any disease condition. Potentized forms of Condurango are used successfully to treat digestive problems, as well as esophageal and stomach cancers. However, the comparative efficacies of Condurango 6C and 30C, one diluted below and one above Avogadro’s limit (lacking original drug molecule, respectively, have not been critically analyzed for their cell-killing (apoptosis efficacy against lung cancer cells in vitro, and signalling cascades have not been studied. Hence, the present study was undertaken. Methods: 3-(4,5-dimethylthiazol-2-yl-2,5-diphenylte- trazolium bromide (MTT assays were conducted on H460-non-small-cell lung cancer (NSCLC cells by using a succussed ethyl alcohol vehicle (placebo as a control. Studies on cellular morphology, cell cycle regulation, generation of reactive oxygen species (ROS, changes in mitochondrial membrane potential (MMP, and DNA-damage were made, and expressions of related signaling markers were studied. The observations were done in a “blinded” manner. Results: Both Condurango 6C and 30C induced apoptosis via cell cycle arrest at subG0/G1 and altered expressions of certain apoptotic markers significantly in H460 cells. The drugs induced oxidative stress through ROS elevation and MMP depolarization at 18-24 hours. These events presumably activated a caspase-3-mediated signalling cascade, as evidenced by reverse transcriptase- polymerase chain reaction (RT-PCR, western blot and immunofluorescence studies at a late phase (48 hours in which cells were pushed towards apoptosis. Conclusion: Condurango 30C had greater apoptotic effect than Condurango 6C as claimed in the homeopathic doctrine.

  2. Radiolabeling and animal experimental studies of anti-breast cancer McAb 6C6 and mouse-human chimeric antibody 6C6CHI

    International Nuclear Information System (INIS)

    Yang Zhi; Hu Xiaoqian; Li Erqiu

    2003-01-01

    The aim of this work is to study bio-distribution and tumor absorption of anti breast cancer monoclonal antibody 6C6 and its chimeric antibody 6C6-CHI. The modified Schwartz method was employed to label 6C6 and 6C6CHI with 99 Tc m . The labeled antibody was injected to mouse via tail vein and the blood clearance and whole body clearance were observed. Nude mice bearing breast cancer MCF7 were injected with 99 Tc m -labeled antibody and the bio-distribution was studied and imaged with γ-ray camera. The yield of the two labeled antibodies was more than 90% and their immunoactivities were more than 80%. The whole body eliminated half-time of 99 Tc m -6C6 was 4.1h, and the half-times in blood were T α =0.55h and T β =12.42h respectively. The whole body half-time of 99 Tc m -6C6CHI was 4.28h and the half-times in blood were T α =0.98h and T β =12.42h respectively. The bio-distribution of nude mice bearing breast cancer MCF7 cells was as follows: the ID%/g of tumor and blood was (7.42±0.85) and (5.67±1.44) respectively at 23h after injection of 99 Tc m -6C6. The T/NT (tumor to non tumor) ratios were all more than 1.0 except kidney and the ID%/g of tumor and blood was (4.23±0.64) and (6.97±0.23) respectively at 23 h after injection of 99 Tc m -6C6CHI. The T/NT (tumor to non tumor) ratios were all more than 1.0 except blood and kidney. The γ imaging results showed that the tumor was imaged clearly at 24h after injection of radiolabeled antibodies and the other organs did not concentrate the antibodies except kidney. Anti-breast cancer monoclonal antibody 6C6 can be well located in tumor. Although ID%/g of tumor of the chimeric antibody 6C6CHI was slightly lower than that of 6C6 antibody, and ID%/g of blood was higher than that of 6C6, the tumor imaging of 6C6-CHI was also clear

  3. Talking about cancer with confidence: evaluation of cancer awareness training for community-based health workers.

    Science.gov (United States)

    Grimmett, Chloe; Macherianakis, Alexis; Rendell, Helen; George, Helen; Kaplan, Gwen; Kilgour, Gillian; Power, Emily

    2014-09-01

    To examine the impact of cancer awareness training for community-based health workers on confidence to talk about cancer, and knowledge of cancer risk factors and signs and symptoms. Community-based health workers from Sandwell, Birmingham and Solihull were invited to take part in one of 14 one-day training workshops. Trainees completed questionnaires at the beginning of the workshop and were followed up one month later. Confidence in talking about cancer was examined. Knowledge of cancer risk factors and signs and symptoms was assessed. Trainees were asked to rate the usefulness of the workshop, whether they would recommend it to others and whether they had put what they had learnt into practice. A total of 187 community-based health workers took part in the workshops, and 167 (89%) completed the one-month follow-up. Considerable improvements were observed in confidence to discuss cancer. For example, the proportion of participants reporting feeling 'very confident'/'fairly confident' in discussing signs and symptoms of cancer increased from 32% to 96% (p cancer at one month compared with 21% before training (p cancer signs and symptoms also increased from 2.3 (± 1.6) to 2.7 (± 1.5), (p = .02). Most trainees (83%) rated the workshop as 'very useful', and 89% said they would 'definitely' recommend the workshop. The cancer awareness training was reviewed positively by community-based health workers and led to improvements in confidence to talk about cancer, and knowledge of risk factors and warning signs of cancer. It is hoped that raising awareness among this group will help them to communicate and drive behaviour change in the at-risk populations with whom they work. © Royal Society for Public Health 2014.

  4. HFE gene C282Y variant is associated with colorectal cancer in Caucasians: a meta-analysis.

    Science.gov (United States)

    Chen, Weidong; Zhao, Hua; Li, Tiegang; Yao, Hongliang

    2013-08-01

    The HFE gene has been suggested to play an important role in the pathogenesis of colorectal cancer. However, the results have been conflicting. In this study, we performed a meta-analysis to clarify the association of HFE gene C282Y variant with colorectal cancer. PubMed and Embase were retrieved to identify the potential literature. Pooled odds ratio (OR) with 95 % confidence interval (CI) was calculated using fixed- or random-effects model. A total of eight papers including nine studies (7,588 colorectal cancer cases and 81,571 controls) for HFE gene C282Y variant were included in the meta-analysis. The result indicated that HFE gene C282Y variant was significantly associated with colorectal cancer under recessive model (OR = 2.00, 95 % CI = 1.32-3.04), with no evidence of between-study heterogeneity (I (2) = 0.2 %, p = 0.432). Further subgroup analysis by number of cases suggested the effect was significant in studies with more than 500 cases (OR = 2.51, 95 % CI = 1.58-3.98, I (2) = 0.0 %, p = 0.921), but not in studies with less than 500 cases (OR = 0.75, 95 % CI = 0.28-1.97, I (2) = 0.0 %, p = 0.622). The current meta-analysis supported the positive association of HFE gene C282Y variant with colorectal cancer. Further large-scale studies with the consideration for gene-gene/gene-environment interactions should be conducted to investigate the association.

  5. Lactate Transporters Expression in Tumor of Balb/c Mice Bearing Breast Cancer after Endurance Training

    Directory of Open Access Journals (Sweden)

    M Aveseh

    2014-10-01

    Full Text Available Background & aim: Changes in the metabolism of cancer cells plays a major role in the survival and their expansion. The aim of this study was to determine expression of lactate transmitters in Balb/c mice with breast cancer after endurance training. Methods: In this experimental study twenty-five Balb C mice were randomly divided into two groups of breast cancer control (N=13 and breast cancer training (N=12. Breast cancer was induced in mammary fat pad by injection of cancer cells (MC4L2 in mice and endurance training protocol was applied for 7 weeks in the experimental group. Tumor volume and MCT1, MCT4, and CD147 expression were measured by micro digital caliper and western blotting technique respectively. Data were analyzed statistically using Student t and Pearson. Results: Significant decreases was found in weight and CD147 expression of tumor after 7 weeks of endurance training in the exercise group compared to the control group. No significant differences were seen in MCT4 expression and tumor volume between the groups (05 / 0p>0.05. Significant correlation was found between tumor MCT1 and CD147 expression (P < 0.05, while the relationship between MCT4 and CD147 expression in tumors was not statistically significant. Conclusion: Endurance training can reduce lactate metabolism in cancer cells through suppression of lactate transporters expression and provides a useful tool in breast cancer treatment or prevention.

  6. The effect of intravenous vitamin C on cancer- and chemotherapy-related fatigue and quality of life

    Directory of Open Access Journals (Sweden)

    Anitra C. Carr

    2014-10-01

    Full Text Available Cancer patients commonly experience a number of symptoms of disease progression and the side effects of radiation therapy and adjuvant chemotherapy, which adversely impact on their quality of life. Fatigue is one of the most common and debilitating symptoms reported by cancer patients and can affect quality of life more than pain. Several recent studies have indicated that intravenous vitamin C alleviates a number of cancer- and chemotherapy-related symptoms, such as fatigue, insomnia, loss of appetite, nausea and pain. Improvements in physical, role, cognitive, emotional and social functioning, as well as an improvement in overall health, were also observed. In this mini review we briefly cover the methods commonly used to assess health-related quality of life in cancer patients, and describe the few recent studies examining the effects of intravenous vitamin C on cancer- and chemotherapy-related quality of life. We discuss potential mechanisms that might explain an improvement in quality of life and also considerations for future studies.

  7. VEGFA GENE POLYMORPHISM (С-2578A, C+936T IN PATIENTS WITH BREAST CANCER

    Directory of Open Access Journals (Sweden)

    A. V. Shevchenko

    2012-01-01

    Full Text Available Abstract. Angiogenesis plays the major role in growth, progression and metastasis of different solid umors. Vascular endothelium growth factor (VEGF is a basic factor of angiogenesis regulation. The aim of present study was to evaluate possible correlations between C-2578A and C+936T VEGFА gene functional polymorphisms, and risk of breast cancer development. An association of -2578AA and -2578СС /+936СС VEGFA polymorphisms with incidence of breast cancer was revealed in our study. Distinct features of VEGFA genotype distribution were found for women with lymphogenic metastases and differences in menstrual status.

  8. Saposin C promotes survival and prevents apoptosis via PI3K/Akt-dependent pathway in prostate cancer cells

    Directory of Open Access Journals (Sweden)

    Lee Tae-Jin

    2004-11-01

    Full Text Available Abstract Background In addition to androgens, growth factors are also implicated in the development and neoplastic growth of the prostate gland. Prosaposin is a potent neurotrophic molecule. Homozygous inactivation of prosaposin in mice has led to the development of a number of abnormalities in the male reproductive system, including atrophy of the prostate gland and inactivation of mitogen-activated protein kinase (MAPK and Akt in prostate epithelial cells. We have recently reported that prosaposin is expressed at a higher level by androgen-independent (AI prostate cancer cells as compared to androgen-sensitive prostate cancer cells or normal prostate epithelial and stromal cells. In addition, we have demonstrated that a synthetic peptide (prosaptide TX14A, derived from the trophic sequence of the saposin C domain of prosaposin, stimulated cell proliferation, migration and invasion and activated the MAPK signaling pathway in prostate cancer cells. The biological significances of saposin C and prosaposin in prostate cancer are not known. Results Here, we report that saposin C, in a cell type-specific and dose-dependent manner, acts as a survival factor, activates the Akt-signaling pathway, down-modulates caspase-3, -7, and -9 expression and/or activity, and decreases the cleaved nuclear substrate of caspase-3 in prostate cancer cells under serum-starvation stress. In addition, prosaptide TX14A, saposin C, or prosaposin decreased the growth-inhibitory effect, caspase-3/7 activity, and apoptotic cell death induced by etoposide. We also discovered that saposin C activates the p42/44 MAP kinase pathway in a pertussis toxin-sensitive and phosphatidylinositol 3-kinase (PI3K /Akt-dependent manner in prostate cancer cells. Our data also show that the anti-apoptotic activity of saposin C is at least partially mediated via PI3K/Akt signaling pathway. Conclusion We postulate that as a mitogenic, survival, and anti-apoptotic factor for prostate cancer cells

  9. 7 CFR 983.89 - Termination.

    Science.gov (United States)

    2010-01-01

    ..., ARIZONA, AND NEW MEXICO Miscellaneous Provisions § 983.89 Termination. (a) The Secretary may at any time..., That such majority has, during such representative period, produced for market more than fifty percent of the volume of such pistachios produced for market, but such termination shall be announced at...

  10. 40 CFR 81.89 - Metropolitan Cheyenne Intrastate Air Quality Control Region.

    Science.gov (United States)

    2010-07-01

    ... Quality Control Region. 81.89 Section 81.89 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY... Air Quality Control Regions § 81.89 Metropolitan Cheyenne Intrastate Air Quality Control Region. The Metropolitan Cheyenne Intrastate Air Quality Control Region (Wyoming) consists of the territorial area...

  11. Prolongation of the survival of breast cancer-bearing mice immunized with GM-CSF-secreting syngeneic/allogeneic fibroblasts transfected with a cDNA expression library from breast cancer cells.

    Science.gov (United States)

    Kim, Tae S; Jung, Mi Y; Cho, Daeho; Cohen, Edward P

    2006-10-30

    Breast cancer cells, like other types of neoplastic cells, form weakly immunogenic tumor-associated antigens. The antigenic properties of the tumor-associated antigens can be enhanced if they are expressed by highly immunogenic cells. In this study, a cancer vaccine was prepared by transfer of a cDNA expression library from SB5b breast carcinoma into mouse fibroblast cells of C3H/He mouse origin (H-2(k)), that had been previously modified to secrete GM-CSF and to express allogeneic class I-determinants (H-2(b)). The transfected syngeneic/allogeneic fibroblasts secreting GM-CSF were used as a vaccine in C3H/He mice. Robust cell-mediated immunity toward the breast cancer cells was generated in mice immunized with the cDNA-based vaccine. The immunity, mediated predominantly by CD8(+) T lymphocytes, was directed toward the breast cancer cells, but not against either of two other non-cross-reactive neoplasms of C3H/He mice. The immunity was sufficient to prolong the survival of mice with established breast cancer. Among other advantages, preparation of the vaccine by cDNA-transfer into a fibroblast cell line enabled the recipient cells to be modified in advance of DNA-transfer to augment their immunogenic properties. As the transferred DNA is replicated as the transfected cells divide, the vaccine could be prepared from microgram quantities of tumor tissue.

  12. HER-2-PET imaging with Zr-89-trastuzumab in metastatic breast cancer patients

    NARCIS (Netherlands)

    Munnink, T. Oude; Dijkers, E.; Hooge, M. Lub-de; Kosterink, J.; Brouwers, A.; de Jong, J. R.; van Dongen, G.; de Vries, E.

    2009-01-01

    1045 Background: Non-invasive diagnostic tools can optimize and evaluate HER2 directed therapy in HER2 positive breast cancer patients. HER2 imaging with (111)In-trastuzumab SPECT showed promising results (Perik et al, J Clin Oncol. 2006). To further optimize HER2 imaging, we developed

  13. miR-221 stimulates breast cancer cells and cancer-associated fibroblasts (CAFs) through selective interference with the A20/c-Rel/CTGF signaling.

    Science.gov (United States)

    Santolla, Maria Francesca; Lappano, Rosamaria; Cirillo, Francesca; Rigiracciolo, Damiano Cosimo; Sebastiani, Anna; Abonante, Sergio; Tassone, Pierfrancesco; Tagliaferri, Pierosandro; Di Martino, Maria Teresa; Maggiolini, Marcello; Vivacqua, Adele

    2018-05-02

    MicroRNA (miRNAs) are non-coding small RNA molecules that regulate gene expression by inhibiting the translation of target mRNAs. Among several dysregulated miRNAs in human cancer, the up-regulation of miR-221 has been associated with development of a variety of hematologic and solid malignancies. In this study, we investigated the involvement of miR-221 in breast cancer. TaqMan microRNA assay was used to detect the miR-221 levels in normal cells and in MDA-MB 231 and SkBr3 breast cancer cells as well as in main players of the tumor microenvironment, namely cancer-associated fibroblasts (CAFs). miR-221 mimic sequence and locked nucleic acid (LNA)-i-miR-221 construct were used to induce or inhibit, respectively, the miR-221 expression in cells used. Quantitative PCR and western blotting analysis were performed to evaluate the levels of the miR-221 target gene A20 (TNFAIP3), as well as the member of the NF-kB complex namely c-Rel and the connective tissue growth factor (CTGF). Chromatin immunoprecipitation (ChIP) assay was performed to ascertain the recruitment of c-Rel to the CTFG promoter. Finally, the cell growth and migration in the presence of LNA-i-miR-221 or silencing c-Rel and CTGF by specific short hairpin were assessed by cell count, colony formation and boyden chambers assays. Statistical analysis was performed by ANOVA. We first demonstrated that LNA-i-miR-221 inhibits both endogenous and ectopic expression of miR-221 in our experimental models. Next, we found that the A20 down-regulation, as well as the up-regulation of c-Rel induced by miR-221 were no longer evident using LNA-i-miR-221. Moreover, we established that the miR-221 dependent recruitment of c-Rel to the NF-kB binding site located within the CTGF promoter region is prevented by using LNA-i-miR-221. Furthermore, we determined that the up-regulation of CTGF mRNA and protein levels by miR-221 is no longer evident using LNA-i-miR221 and silencing c-Rel. Finally, we assessed that cell growth and

  14. c-MET Overexpression in Colorectal Cancer: A Poor Prognostic Factor for Survival.

    Science.gov (United States)

    Lee, Su Jin; Lee, Jeeyun; Park, Se Hoon; Park, Joon Oh; Lim, Ho Yeong; Kang, Won Ki; Park, Young Suk; Kim, Seung Tae

    2018-03-02

    Increased mesenchymal-epithelial transition factor gene (c-MET) expression in several human malignancies is related to increased tumor progression and is a new potential drug target for several types of cancers. In the present study, we investigated the incidence of c-MET overexpression and its prognostic significance in patients with colorectal cancer (CRC). We retrospectively reviewed the data from 255 stage IV CRC patients who had results from a c-MET immunohistochemical test at Samsung Medical Center. We explored the relationships between c-MET overexpression and clinicopathological features and survival. Primary tumor sites were 67 right-sided colon, 98 left-sided colon, and 90 rectum. Forty-two patients (16.7%) had poorly differentiated or mucinous carcinoma. Among the 255 patients, 39 (15.3%) exhibited c-MET overexpression. There was no significant difference in the prevalence of c-MET overexpression according to primary site, histologic differentiation, molecular markers, or metastatic sites. In a comparison of the tumor response to first-line chemotherapy according to the level of c-MET expression, we found no significant difference in either partial response or disease control rate. In the survival analysis, patients with c-MET overexpression had significantly shorter overall survival (39 vs. 27 months; P = .018) and progression-free survival (PFS) during bevacizumab treatment (10 vs. 7 months; P = .024). c-MET overexpression, which was detected in 39 CRC patients (15.3%) irrespective of primary sites or molecular markers, indicated a poor survival prognosis and predicted shorter PFS during bevacizumab treatment in patients with CRC. Further studies are warranted to elucidate the value of c-MET-targeted therapy in CRC patients. Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.

  15. 40 CFR 8.9 - Measures to assess and verify environmental impacts.

    Science.gov (United States)

    2010-07-01

    ... environmental impacts. 8.9 Section 8.9 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY GENERAL ENVIRONMENTAL IMPACT ASSESSMENT OF NONGOVERNMENTAL ACTIVITIES IN ANTARCTICA § 8.9 Measures to assess and verify environmental impacts. (a) The operator shall conduct appropriate monitoring of key environmental indicators as...

  16. Mapping cancer cell metabolism with 13 C flux analysis: Recent progress and future challenges

    Directory of Open Access Journals (Sweden)

    Casey Scott Duckwall

    2013-01-01

    Full Text Available The reprogramming of energy metabolism is emerging as an important molecular hallmark of cancer cells. Recent discoveries linking specific metabolic alterations to cancer development have strengthened the idea that altered metabolism is more than a side effect of malignant transformation, but may in fact be a functional driver of tumor growth and progression in some cancers. As a result, dysregulated metabolic pathways have become attractive targets for cancer therapeutics. This review highlights the application of 13 C metabolic flux analysis (MFA to map the flow of carbon through intracellular biochemical pathways of cancer cells. We summarize several recent applications of MFA that have identified novel biosynthetic pathways involved in cancer cell proliferation and shed light on the role of specific oncogenes in regulating these pathways. Through such studies, it has become apparent that the metabolic phenotypes of cancer cells are not as homogeneous as once thought, but instead depend strongly on the molecular alterations and environmental factors at play in each case.

  17. Overexpressed DNA polymerase iota regulated by JNK/c-Jun contributes to hypermutagenesis in bladder cancer.

    Science.gov (United States)

    Yuan, Fang; Xu, Zhigang; Yang, Mingzhen; Wei, Quanfang; Zhang, Yi; Yu, Jin; Zhi, Yi; Liu, Yang; Chen, Zhiwen; Yang, Jin

    2013-01-01

    Human DNA polymerase iota (pol ι) possesses high error-prone DNA replication features and performs translesion DNA synthesis. It may be specialized and strictly regulated in normal mammalian cells. Dysregulation of pol ι may contribute to the acquisition of a mutator phenotype. However, there are few reports describing the transcription regulatory mechanism of pol ι, and there is controversy regarding its role in carcinogenesis. In this study, we performed the deletion and point-mutation experiment, EMSA, ChIP, RNA interference and western blot assay to prove that c-Jun activated by c-Jun N-terminal kinase (JNK) regulates the transcription of pol ι in normal and cancer cells. Xeroderma pigmentosum group C protein (XPC) and ataxia-telangiectasia mutated related protein (ATR) promote early JNK activation in response to DNA damage and consequently enhance the expression of pol ι, indicating that the novel role of JNK signal pathway is involved in DNA damage response. Furthermore, associated with elevated c-Jun activity, the overexpression of pol ι is positively correlated with the clinical tumor grade in 97 bladder cancer samples and may contribute to the hypermutagenesis. The overexpressed pol ι-involved mutagenesis is dependent on JNK/c-Jun pathway in bladder cancer cells identifying by the special mutation spectra. Our results support the conclusion that dysregulation of pol ι by JNK/c-Jun is involved in carcinogenesis and offer a novel understanding of the role of pol ι or c-Jun in mutagenesis.

  18. 40 CFR 89.507 - Sample selection.

    Science.gov (United States)

    2010-07-01

    ... Auditing § 89.507 Sample selection. (a) Engines comprising a test sample will be selected at the location...). However, once the manufacturer ships any test engine, it relinquishes the prerogative to conduct retests...

  19. The dynamics of accumulation and disappearance of {sup 89}Sr in tea

    Energy Technology Data Exchange (ETDEWEB)

    Chuanqun, Chen; Shouxiang, Wang; Yongxi, Zhang; Zhiming, Sun [Zhejiang Agricultural Univ., Hangzhou (China). Inst. of Nuclear Agricultural Sciences

    1994-06-01

    The {sup 89}Sr was put into a tea tree-soil system by different ways. The results showed that for {sup 89}Sr put into the system through the above-ground 1 part of tea tree, its concentration in tea was much higher than that through soil. The concentration of {sup 89}Sr in older tea was higher than that in shoot for the same treatment. The accumulation and disappearance of {sup 89}Sr in tea varied with the treatments. For the treatment through the above-ground part, the concentrations of {sup 89}Sr in older tea and shoot were monotonously decreasing with time. For the treatment through soil the concentration of {sup 89}Sr in shoot increased initially to a maximum value, then decreased slowly; while the concentration of {sup 89}Sr in older tea increased quickly in a definite period, then increased slowly to gain a saturated value. In addition, the values of concentration factor of {sup 89}Sr in the older tea and shoot were determined, too.

  20. Mapping of Powdery Mildew Resistance Gene pmCH89 in a Putative Wheat-Thinopyrum intermedium Introgression Line.

    Science.gov (United States)

    Hou, Liyuan; Zhang, Xiaojun; Li, Xin; Jia, Juqing; Yang, Huizhen; Zhan, Haixian; Qiao, Linyi; Guo, Huijuan; Chang, Zhijian

    2015-07-28

    Powdery mildew, caused by Blumeria graminis f. sp. tritici (Bgt), is a globally serious disease adversely affecting wheat production. The Bgt-resistant wheat breeding line CH09W89 was derived after backcrossing a Bgt resistant wheat-Thinopyrum intermedium partial amphiploid TAI7045 with susceptible wheat cultivars. At the seedling stage, CH09W89 exhibited immunity or high resistance to Bgt pathotypes E09, E20, E21, E23, E26, Bg1, and Bg2, similar to its donor line TAI7045 and Th. intermedium. No Th. intermedium chromatin was detected based on genomic in situ hybridization of mitotic chromosomes. To determine the mode of inheritance of the Bgt resistance and the chromosomal location of the resistance gene, CH09W89 was crossed with two susceptible wheat cultivars. The results of the genetic analysis showed that the adult resistance to Bgt E09 in CH09W89 was controlled by a single recessive gene, which was tentatively designated as pmCH89. Two polymorphic SSR markers, Xwmc310 and Xwmc125, were linked to the resistance gene with genetic distances 3.1 and 2.7 cM, respectively. Using the Chinese Spring aneuploid and deletion lines, the resistance gene and its linked markers were assigned to chromosome arm 4BL in the bin 0.68-0.78. Due to its unique position on chromosome 4BL, pmCH89 appears to be a new locus for resistance to powdery mildew. These results will be of benefit for improving powdery mildew resistance in wheat breeding programs.

  1. Study of Malformin C, a Fungal Source Cyclic Pentapeptide, as an Anti-Cancer Drug.

    Directory of Open Access Journals (Sweden)

    Jing Wang

    Full Text Available Malformin C, a fungal cyclic pentapeptide, has been claimed to have anti-cancer potential, but no in vivo study was available to substantiate this property. Therefore, we conducted in vitro and in vivo experiments to investigate its anti-cancer effects and toxicity. Our studies showed Malformin C inhibited Colon 38 and HCT 116 cell growth dose-dependently with an IC50 of 0.27±0.07μM and 0.18±0.023μM respectively. This inhibition was explicated by Malformin C's effect on G2/M arrest. Moreover, we observed up-regulated expression of phospho-histone H2A.X, p53, cleaved CASPASE 3 and LC3 after Malformin C treatment, while the apoptosis assay indicated an increased population of necrotic and late apoptotic cells. In vivo, the pathological study exhibited the acute toxicity of Malformin C at lethal dosage in BDF1 mice might be caused by an acute yet subtle inflammatory response, consistent with elevated IL-6 in the plasma cytokine assay. Further anti-tumor and toxicity experiments proved that 0.3mg/kg injected weekly was the best therapeutic dosage of Malformin C in Colon 38 xenografted BDF1 mice, whereas 0.1mg/kg every other day showed no effect with higher resistance, and 0.9mg/kg per week either led to fatal toxicity in seven-week old mice or displayed no advantage over 0.3mg/kg group in nine-week old mice. Overall, we conclude that Malformin C arrests Colon 38 cells in G2/M phase and induces multiple forms of cell death through necrosis, apoptosis and autophagy. Malformin C has potent cell growth inhibition activity, but the therapeutic index is too low to be an anti-cancer drug.

  2. Identification of Epigenetic Changes in Prostate Cancer using Induced Pluripotent Stem Cells

    Science.gov (United States)

    2013-04-01

    NDUFA12,CYC1,DHODH,NDUFA2,COX7C Melanoma Signaling 8.10E-01 6.52E-02 PIK3C3,CDK4,MDM2 Maturity Onset Diabetes of Young ( MODY ) Signaling 7.99E-01 6.45E...ACTG1,CACNA1A Inhibition of Angiogenesis by TSP1 1.63E+00 1.03E-01 CD47,SDC1,GUCY1A3,MAPK10 Type I Diabetes Mellitus Signaling 1.61E+00 6.67E-02...Pathway 5.02E-01 5.71E-02 CCNH,POLR2K Type II Diabetes Mellitus Signaling 4.89E-01 3.11E-02 MAP3K7,PIK3C3,MAPK10,SOCS5,PRKCB Hereditary Breast Cancer

  3. Reduced rate of human papillomavirus infection and genetic overtransmission of TP53 72C polymorphic variant lower cervical cancer incidence.

    Science.gov (United States)

    Alsbeih, Ghazi A; Al-Harbi, Najla M; Bin Judia, Sara S; Khoja, Hatim A; Shoukri, Mohamed M; Tulbah, Asma M

    2017-07-01

    Cervical cancer is a predominantly human papillomavirus (HPV)-driven disease worldwide. However, its incidence is unexplainably low in western Asia, including Saudi Arabia. Using this paradigm, we investigated the role of HPV infection rate and host genetic predisposition in TP53 G72C single nucleotide polymorphism (SNP) presumed to affect cancer incidence. Patients treated between 1990 and 2012 were reviewed, and a series of 232 invasive cervical cancer cases were studied and compared with 313 matched controls without cancer. SNP was genotyped by way of direct sequencing. HPV linear array analysis was used to detect and genotype HPV in tumor samples. The incidence of cervical cancer revealed bimodal peaks at 42.5 years, with a slighter rebound at 60.8 years. Among all cases, 77% were HPV-positive and 16 HPV genotypes were detected-mostly genotypes 16 (75%) and 18 (9%)-with no difference by age, histology, or geographical region. Although the TP53 G72C genotype was not associated with overall cervical cancer risk, it was significantly associated with HPV positivity (odds ratio, 0.57; 95% confidence interval, 0.36-0.90; P = .016). Furthermore, the variant C allele was significantly overtransmitted in the population (P Cervical cancer incidence displays bimodal curve peaking at a young age with secondary rebound at older age. The combination of relative low HPV infection and variant TP53 72C allele overtransmission provide a plausible explanation for the low incidence of cervical cancer in our population. Therefore, HPV screening and host SNP genotyping may provide more relevant biomarkers to gauge the risk of developing cervical cancer. Cancer 2017;123:2459-66. © 2017 American Cancer Society. © 2017 The Authors. Cancer published by Wiley Periodicals, Inc. on behalf of American Cancer Society.

  4. Heterogeneity of d-glucuronyl C5-epimerase expression and epigenetic regulation in prostate cancer

    International Nuclear Information System (INIS)

    Prudnikova, Tatiana Y; Soulitzis, Nikolaos; Kutsenko, Olesya S; Mostovich, Lyudmila A; Haraldson, Klas; Ernberg, Ingemar; Kashuba, Vladimir I; Spandidos, Demetrios A; Zabarovsky, Eugene R; Grigorieva, Elvira V

    2013-01-01

    Heparansulfate proteoglycans (HSPG) play an important role in cell–cell and cell–matrix interactions and signaling, and one of the key enzymes in heparansulfate biosynthesis is d-glucuronyl C5-epimerase (GLCE). A tumor suppressor function has been demonstrated for GLCE in breast and lung carcinogenesis; however, no data are available as to the expression and regulation of the gene in prostate cancer. In this study, decreased GLCE expression was observed in 10% of benign prostate hyperplasia (BPH) tissues and 53% of prostate tumors, and increased GLCE mRNA levels were detected in 49% of BPH tissues and 21% of tumors. Statistical analysis showed a positive correlation between increased GLCE expression and Gleason score, TNM staging, and prostate-specific antigen (PSA) level in the prostate tumors (Pearson correlation coefficients GLCE/Gleason = 0.56, P < 0.05; GLCE/TNM = 0.62, P < 0.05; and GLCE/PSA = 0.88, P < 0.01), suggesting GLCE as a candidate molecular marker for advanced prostate cancer. Immunohistochemical analysis revealed an intratumoral heterogeneity of GLCE protein levels both in BPH and prostate cancer cells, resulting in a mixed population of GLCE-expressing and nonexpressing epithelial cells in vivo. A model experiment on normal (PNT2) and prostate cancer (LNCaP, PC3, DU145) cell lines in vitro showed a 1.5- to 2.5-fold difference in GLCE expression levels between the cancer cell lines and an overall decrease in GLCE expression in cancer cells. Methyl-specific polymerase chain reaction (PCR), bisulfite sequencing, and deoxy-azacytidin (aza-dC) treatment identified differential GLCE promoter methylation (LNCaP 70–72%, PC3 32–35%, DU145, and PNT2 no methylation), which seems to contribute to heterogeneous GLCE expression in prostate tumors. The obtained results reveal the complex deregulation of GLCE expression in prostatic diseases compared with normal prostate tissue and suggest that GLCE may be used as a potential model to study the functional

  5. Post-cancer Treatment with Condurango 30C Shows Amelioration of Benzo[a]pyrene-induced Lung Cancer in Rats Through the Molecular Pathway of Caspa- se-3-mediated Apoptosis Induction

    Directory of Open Access Journals (Sweden)

    Sikdar Sourav

    2013-09-01

    Full Text Available Objectives: The present investigation aimed at examining if post-cancer treatment with a potentized homeopathic drug, Condurango 30C, which is generally used to treat oesophageal cancer, could also show an ameliorating effect through apoptosis induction on lung cancer induced by benzo[a]pyrene (BaP in white rats (Rattus norvegicus. Methods: Lung cancer was induced after four months by chronic feeding of BaP to rats through gavage at a dose of 50 mg/kg body weight for one month. After four months, the lung-cancer-bearing rats were treated with Condurango 30C for the next one (5th, two (5th-6th and three (5th-7th months, respectively, and were sacrificed at the corresponding time- points. The ameliorating effect, if any, after Condurango 30C treatment for the various periods was evaluated by using protocols such as histology, scanning electron microscopy (SEM, annexinV-FITC/PI assay, flow cytometry of the apoptosis marker, DNA fragmentation, reverse transcriptase-polymerase chain reaction (RT-PCR, immunohistochemistry, and western blot analyses of lung tissue samples. Results: Striking recovery of lung tissue to a near normal status was noticed after post-cancerous drug treatment, as evidenced by SEM and histology, especially after one and two months of drug treatment. Data from the annexinV-FITC/PI and DNA fragmentation assays revealed that Condurango 30C could induce apoptosis in cancer cells after post-cancer treatment. A critical analysis of signalling cascade, evidenced through a RT-PCR study, demonstrated up-regulation and down-regulation of different pro- and anti-apoptotic genes, respectively, related to a caspase-3-mediated apoptotic pathway, which was especially discernible after one-month and two- month drug treatments. Correspondingly, Western blot and immunohistochemistry studies confirmed the ameliorative potential of Condurango 30C by its ability to down-regulate the elevated epidermal growth factor receptor (EGFR expression, a

  6. Vitamin C - A new player in regulation of the cancer epigenome

    DEFF Research Database (Denmark)

    Gillberg, Linn; Ørskov, Andreas D.; Liu, Minmin

    2017-01-01

    of pharmacological doses of vitamin C injected intravenously to selectively kill tumor cells. This review will focus on the potential of vitamin C to optimize the outcome of epigenetic therapy in cancer patients and alternatively to act as a therapeutic at high doses.......Over the past few years it has become clear that vitamin C, as a provider of reduced iron, is an essential factor for the function of epigenetic regulators that initiate the demethylation of DNA and histones. Vitamin C deficiency is rare in the general population, but is frequently observed...... of care. Recent in vitro studies suggest that vitamin C at physiological concentrations, combined with hypomethylating agents may act synergistically to cause DNA demethylation through active and passive mechanisms, respectively. Additionally, several recent studies have renewed interest in the use...

  7. High-Dose Vitamin C Injection to Cancer Patients May Promote Thrombosis Through Procoagulant Activation of Erythrocytes.

    Science.gov (United States)

    Kim, Keunyoung; Bae, Ok-Nam; Koh, Sung-Hee; Kang, Seojin; Lim, Kyung-Min; Noh, Ji-Yoon; Shin, Sue; Kim, Inho; Chung, Jin-Ho

    2015-10-01

    Potential risk of high-dose vitamin C consumption is often ignored. Recently, gram-dose vitamin C is being intravenously injected for the treatment of cancer, which can expose circulating blood cells to extremely high concentrations of vitamin C. As well as platelets, red blood cells (RBCs) can actively participate in thrombosis through procoagulant activation. Here, we examined the procoagulant and prothrombotic risks associated with the intravenous injection of gram-dose vitamin C. Vitamin C (0.5-5 mM) increased procoagulant activity of freshly isolated human RBCs via the externalization of phosphatidylserine (PS) to outer cellular membrane and the formation of PS-bearing microvesicles. PS exposure was induced by the dysregulation of key enzymes for the maintenance of membrane phospholipid asymmetry, which was from vitamin C-induced oxidative stress, and resultant disruption of calcium and thiol homeostasis. Indeed, the intravenous injection of vitamin C (0.5-1.0 g/kg) in rats in vivo significantly increased thrombosis. Notably, the prothrombotic effects of vitamin C were more prominent in RBCs isolated from cancer patients, who are at increased risks of thrombotic events. Vitamin C-induced procoagulant and prothrombotic activation of RBCs, and increased thrombosis in vivo. RBCs from cancer patients exhibited increased sensitivity to the prothrombotic effects of vitamin C, reflecting that intravenous gram-dose vitamin C therapy needs to be carefully revisited. © The Author 2015. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  8. Insulin secretagogue use and circulating inflammatory C–C chemokine levels in breast cancer patients

    Directory of Open Access Journals (Sweden)

    Zachary A.P. Wintrob

    2017-04-01

    Studied plasma samples were collected under a previously reported study design involving a population of women diagnosed with breast cancer presenting with or without type 2 diabetes mellitus at the time of breast cancer diagnosis (Wintrob et al., 2017, 2016 [1,2]. The data presented here shows the relationship between pre-existing use of insulin secretagogue, the inflammatory C–C chemokine profiles at the time of breast cancer diagnosis, and subsequent cancer outcomes. A Pearson correlation analysis stratified by secretagogue use and controls was implemented to evaluate the relationship between the investigated biomarkers and respectively each of these biomarkers and the other relevant reported cytokine datasets derived from the same patient population (Wintrob et al., 2017, 2016 [1,2].

  9. 27 CFR 479.89 - Transfers to the United States.

    Science.gov (United States)

    2010-04-01

    ... Transfers to the United States. A firearm may be transferred to the United States or any department... 27 Alcohol, Tobacco Products and Firearms 3 2010-04-01 2010-04-01 false Transfers to the United States. 479.89 Section 479.89 Alcohol, Tobacco Products, and Firearms BUREAU OF ALCOHOL, TOBACCO...

  10. YKL-40/c-Met expression in rectal cancer biopsies predicts tumor regression following neoadjuvant chemoradiotherapy: a multi-institutional study.

    Science.gov (United States)

    Senetta, Rebecca; Duregon, Eleonora; Sonetto, Cristina; Spadi, Rossella; Mistrangelo, Massimiliano; Racca, Patrizia; Chiusa, Luigi; Munoz, Fernando H; Ricardi, Umberto; Arezzo, Alberto; Cassenti, Adele; Castellano, Isabella; Papotti, Mauro; Morino, Mario; Risio, Mauro; Cassoni, Paola

    2015-01-01

    Neoadjuvant chemo-radiotherapy (CRT) followed by surgical resection is the standard treatment for locally advanced rectal cancer, although complete tumor pathological regression is achieved in only up to 30% of cases. A clinicopathological and molecular predictive stratification of patients with advanced rectal cancer is still lacking. Here, c-Met and YKL-40 have been studied as putative predictors of CRT response in rectal cancer, due to their reported involvement in chemoradioresistance in various solid tumors. A multicentric study was designed to assess the role of c-Met and YKL-40 expression in predicting chemoradioresistance and to correlate clinical and pathological features with CRT response. Immunohistochemistry and fluorescent in situ hybridization for c-Met were performed on 81 rectal cancer biopsies from patients with locally advanced rectal adenocarcinoma. All patients underwent standard (50.4 gy in 28 fractions + concurrent capecitabine 825 mg/m2) neoadjuvant CRT or the XELOXART protocol. CRT response was documented on surgical resection specimens and recorded as tumor regression grade (TRG) according to the Mandard criteria. A significant correlation between c-Met and YKL-40 expression was observed (R = 0.43). The expressions of c-Met and YKL-40 were both significantly associated with a lack of complete response (86% and 87% of c-Met and YKL-40 positive cases, prectal cancer. Targeted therapy protocols could take advantage of prior evaluations of c-MET and YKL-40 expression levels to increase therapeutic efficacy.

  11. Prevalence of Helicobacter Pylori in gastric cancer in a south-east Asian population by 14C-urea breath test

    International Nuclear Information System (INIS)

    Chung, A.Y-F; Chow, P.K.H.; Yu, W-K.; Ho, J.M.S.; Chan, H-S.; Wong, W-K.; Soo, K-C.

    2001-01-01

    Helicobacter pylori is believed to play an important role in the aetiology of gastric cancer. There is a great variability in seropositivity and histological frequency of H. pylori in gastric cancer. The present prospective study investigates the prevalence of H. pylori infection in gastric cancer patients using 14C-urea breath testing. Patients with endoscopic biopsy-proven gastric cancer were fasted for 6 h prior to ingesting 18.5 x 104 Bq of 14C-urea cocktail orally. Breath samples were collected after 20 min by AS/King them to blow into a hyamine solution and measurements were read in a scintillation counter. Fifty out of 51 patients (98%) with gastric cancer were positive on the 14C-urea breath test compared to 29 patients (61%) who were positive on histology. There was no association between sex, age or tumour site, stage, differentiation, Lauren type and H. pylori status. The test was negative in one patient with cardiac tumour in which histology of the resected specimen was also negative for the bacteria. Active H. pylori infection is highly prevalent in gastric cancer in a South-East Asian population. The 14C-urea breath test is a highly sensitive method for detecting the presence of H. pylori even in gastric adenocarcinoma irrespective of the stage

  12. Association of common ATM variants with familial breast cancer in a South American population

    International Nuclear Information System (INIS)

    González-Hormazábal, Patricio; Jara, Lilian; Bravo, Teresa; Blanco, Rafael; Valenzuela, Carlos Y; Gómez, Fernando; Waugh, Enrique; Peralta, Octavio; Ortuzar, Waldo; Reyes, Jose M

    2008-01-01

    The ATM gene has been frequently involved in hereditary breast cancer as a low-penetrance susceptibility gene but evidence regarding the role of ATM as a breast cancer susceptibility gene has been contradictory. In this study, a full mutation analysis of the ATM gene was carried out in patients from 137 Chilean breast cancer families, of which 126 were BRCA1/2 negatives and 11 BRCA1/2 positives. We further perform a case-control study between the subgroup of 126 cases BRCA1/2 negatives and 200 controls for the 5557G>A missense variant and the IVS38-8T>C and the IVS24-9delT polymorphisms. In the full mutation analysis we detected two missense variants and eight intronic polymorphisms. Carriers of the variant IVS24-9delT, or IVS38-8T>C, or 5557G>A showed an increase in breast cancer risk. The higher significance was observed in the carriers of IVS38-8T>C (OR = 3.09 [95%CI 1.11–8.59], p = 0.024). The IVS24-9 T/(-T), IVS38-8 T/C, 5557 G/A composite genotype confered a 3.19 fold increase in breast cancer risk (OR = 3.19 [95%CI 1.16–8.89], p = 0.021). The haplotype estimation suggested a strong linkage disequilibrium between the three markers (D' = 1). We detected only three haplotypes in the cases and control samples, some of these may be founder haplotypes in the Chilean population. The IVS24-9 T/(-T), IVS38-8 T/C, 5557 G/A composite genotype alone or in combination with certain genetic background and/or environmental factors, could modify the cancer risk by increasing genetic inestability or by altering the effect of the normal DNA damage response

  13. Kempopeptin C, a Novel Marine-Derived Serine Protease Inhibitor Targeting Invasive Breast Cancer

    Directory of Open Access Journals (Sweden)

    Fatma H. Al-Awadhi

    2017-09-01

    Full Text Available Kempopeptin C, a novel chlorinated analogue of kempopeptin B, was discovered from a marine cyanobacterium collected from Kemp Channel in Florida. The structure was elucidated using NMR spectroscopy and mass spectrometry (MS. The presence of the basic Lys residue adjacent to the N-terminus of the 3-amino-6-hydroxy-2-piperidone (Ahp moiety contributed to its selectivity towards trypsin and related proteases. The antiproteolytic activity of kempopeptin C was evaluated against trypsin, plasmin and matriptase and found to inhibit these enzymes with IC50 values of 0.19, 0.36 and 0.28 μM, respectively. Due to the significance of these proteases in cancer progression and metastasis, as well as their functional redundancy with respect to targeting overlapping substrates, we examined the effect of kempopeptin C on the downstream cellular substrates of matriptase: CDCP1 and desmoglein-2 (Dsg-2. Kempopeptin C was shown to inhibit the cleavage of both substrates in vitro. Additionally, kempopeptin C reduced the cleavage of CDCP1 in MDA-MB-231 cells up to 10 µM. The functional relevance of targeting matriptase and related proteases was investigated by assessing the effect of kempopeptin C on the migration of breast cancer cells. Kempopeptin C inhibited the migration of the invasive MDA-MB-231 cells by 37 and 60% at 10 and 20 µM, respectively.

  14. MUC1-C activates EZH2 expression and function in human cancer cells.

    Science.gov (United States)

    Rajabi, Hasan; Hiraki, Masayuki; Tagde, Ashujit; Alam, Maroof; Bouillez, Audrey; Christensen, Camilla L; Samur, Mehmet; Wong, Kwok-Kin; Kufe, Donald

    2017-08-07

    The EZH2 histone methyltransferase is a member of the polycomb repressive complex 2 (PRC2) that is highly expressed in diverse human cancers and is associated with a poor prognosis. MUC1-C is an oncoprotein that is similarly overexpressed in carcinomas and has been linked to epigenetic regulation. A role for MUC1-C in regulating EZH2 and histone methylation is not known. Here, we demonstrate that targeting MUC1-C in diverse human carcinoma cells downregulates EZH2 and other PRC2 components. MUC1-C activates (i) the EZH2 promoter through induction of the pRB→E2F pathway, and (ii) an NF-κB p65 driven enhancer in exon 1. We also show that MUC1-C binds directly to the EZH2 CXC region adjacent to the catalytic SET domain and associates with EZH2 on the CDH1 and BRCA1 promoters. In concert with these results, targeting MUC1-C downregulates EZH2 function as evidenced by (i) global and promoter-specific decreases in H3K27 trimethylation (H3K27me3), and (ii) activation of tumor suppressor genes, including BRCA1. These findings highlight a previously unreported role for MUC1-C in activating EZH2 expression and function in cancer cells.

  15. 14 CFR 135.89 - Pilot requirements: Use of oxygen.

    Science.gov (United States)

    2010-01-01

    ... 14 Aeronautics and Space 3 2010-01-01 2010-01-01 false Pilot requirements: Use of oxygen. 135.89... Operations § 135.89 Pilot requirements: Use of oxygen. (a) Unpressurized aircraft. Each pilot of an... operated with the cabin pressure altitude more than 10,000 feet MSL, each pilot shall comply with paragraph...

  16. Candidate Cancer Allele cDNA Collection | Office of Cancer Genomics

    Science.gov (United States)

    CTD2 researchers at the Broad Institute/DFCI have developed a collection of plasmids including mutant alleles found in sequencing studies of cancer. It includes somatic variants found in lung adenocarcinoma and across other cancer types. The clones enable researchers to characterize the function of the cancer variants in a high throughput experiments. These plasmids are collectively called the “Broad Target Accelerator Plasmid Collections”.

  17. STK15 polymorphisms and association with risk of invasive ovarian cancer.

    Science.gov (United States)

    Dicioccio, Richard A; Song, Honglin; Waterfall, Christy; Kimura, Makoto T; Nagase, Hiroki; McGuire, Valerie; Hogdall, Estrid; Shah, Mitul N; Luben, Robert N; Easton, Douglas F; Jacobs, Ian J; Ponder, Bruce A J; Whittemore, Alice S; Gayther, Simon A; Pharoah, Paul D P; Kruger-Kjaer, Susan

    2004-10-01

    STK15 is a putative oncogene that codes for a centrosome-associated, serine/threonine kinase, the normal function of which is to ensure accurate segregation of chromosomes during mitosis. Amplification of STK15 has been reported in ovarian tumors, suggesting a role in ovarian cancer pathology. STK15 is polymorphic with two single nucleotide substitutions (449t/a and 527g/a) in evolutionarily conserved regions causing amino acid changes (F31I and V57I). Two other nucleotide substitutions (287c/g and 1891g/c) of unknown significance are in 5' and 3' untranslated regions (UTR), respectively. To learn more about the involvement of STK15 in ovarian cancer, we genotyped and haplotyped these polymorphisms in three population-based ovarian cancer case-control studies from the United Kingdom, United States, and Denmark with 1,821 combined cases and 2,467 combined controls and calculated risks for developing ovarian cancer. Genotypes of individual polymorphisms in control groups of the United Kingdom, United States, and Denmark conformed to Hardy-Weinberg equilibrium. In combined cases and combined controls, rare allele frequencies were 0.23 and 0.21 for I31, 0.16 and 0.17 for I57, 0.08 and 0.07 for 5' UTR g, and 0.25 and 0.24 for 3' UTR c, respectively. Using FF common homozygotes of F31I as comparator, there was increased ovarian cancer risk to FI heterozygotes (odds ratio, 1.18; 95% confidence interval, 1.01-1.36), II homozygotes (odds ratio, 1.25; 95% confidence interval, 0.89-1.75), and I31 allele carriers (odds ratio, 1.17; 95% confidence interval, 1.02-1.35) in the combined group data. For either V57I, 5' UTR C/G, or 3' UTR G/C, all genotypic ovarian cancer risks were essentially in unity relative to their respective common homozygotes, VV, cc, or gg. Haplotype analysis of combined group data revealed seven haplotypes with frequencies between 0.02 and 0.5, with c-F-V-g the most common. None of the haplotype-specific risks significantly differed from unity relative to

  18. Valproic acid attenuates skeletal muscle wasting by inhibiting C/EBPβ-regulated atrogin1 expression in cancer cachexia.

    Science.gov (United States)

    Sun, Rulin; Zhang, Santao; Hu, Wenjun; Lu, Xing; Lou, Ning; Yang, Zhende; Chen, Shaoyong; Zhang, Xiaoping; Yang, Hongmei

    2016-07-01

    Muscle wasting is the hallmark of cancer cachexia and is associated with poor quality of life and increased mortality. Valproic acid (VPA), a histone deacetylase (HDAC) inhibitor, has important biological effects in the treatment of muscular dystrophy. To verify whether VPA could ameliorate muscle wasting induced by cancer cachexia, we explored the role of VPA in two cancer cachectic mouse models [induced by colon-26 (C26) adenocarcinoma or Lewis lung carcinoma (LLC)] and atrophied C2C12 myotubes [induced by C26 cell conditioned medium (CCM) or LLC cell conditioned medium (LCM)]. Our data demonstrated that treatment with VPA increased the mass and cross-sectional area of skeletal muscles in tumor-bearing mice. Furthermore, treatment with VPA also increased the diameter of myotubes cultured in conditioned medium. The skeletal muscles in cachectic mice or atrophied myotubes treated with VPA exhibited reduced levels of CCAAT/enhancer binding protein beta (C/EBPβ), resulting in atrogin1 downregulation and the eventual alleviation of muscle wasting and myotube atrophy. Moreover, atrogin1 promoter activity in myotubes was stimulated by CCM via activating the C/EBPβ-responsive cis-element and subsequently inhibited by VPA. In contrast to the effect of VPA on the levels of C/EBPβ, the levels of inactivating forkhead box O3 (FoxO3a) were unaffected. In summary, VPA attenuated muscle wasting and myotube atrophy and reduced C/EBPβ binding to atrogin1 promoter locus in the myotubes. Our discoveries indicate that HDAC inhibition by VPA might be a promising new approach for the preservation of skeletal muscle in cancer cachexia. Copyright © 2016 the American Physiological Society.

  19. Synthesis and labelling of Df-DUPA-Pep with gallium-68 and zirconium-89 as new PSMA ligands

    International Nuclear Information System (INIS)

    Benjamin Baur; Ehab Al-Momani; Noeen Malik; Hans-Juergen Machulla; Reske, S.N.; Christoph Solbach; Elena Andreolli; University of Milano-Bicocca, Milan

    2014-01-01

    Prostate-specific membrane antigen (PSMA) is a cell surface protein that is overexpressed in prostate cancer. Due to the specificity of expression of PSMA, numerous urea-based ligands have been synthesized until now. In the current study, we describe the coupling of the chelator desferrioxamine to DUPA-Pep and the subsequent labelling with Ga-68 and Zr-89 as new PSMA ligands. The labelling step is performed at room temperature and pH 7.5. In both radiosyntheses, the RCYs were higher than 95 % within 10 min, making dispensable any further purification and providing the radiotracers directly applicable for further utilization. (author)

  20. Fibulin-3 negatively regulates ALDH1 via c-MET suppression and increases γ-radiation-induced sensitivity in some pancreatic cancer cell lines

    Energy Technology Data Exchange (ETDEWEB)

    Kim, In-Gyu, E-mail: igkim@kaeri.re.kr [Department of Radiation Biology, Environmental Radiation Research Group, Korea Atomic Energy Research Institute, 989-111 Daedeok-daero, Yuseong-gu, Daejeon 305-353 (Korea, Republic of); Department of Radiation Biotechnology and Applied Radioisotope, Korea University of Science and Technology (UST), 989-111 Daedeok-daero, Yusong-gu, Daejeon 305-353 (Korea, Republic of); Lee, Jae-Ha [Department of Radiation Biology, Environmental Radiation Research Group, Korea Atomic Energy Research Institute, 989-111 Daedeok-daero, Yuseong-gu, Daejeon 305-353 (Korea, Republic of); Department of Radiation Biotechnology and Applied Radioisotope, Korea University of Science and Technology (UST), 989-111 Daedeok-daero, Yusong-gu, Daejeon 305-353 (Korea, Republic of); Kim, Seo-Yoen; Kim, Jeong-Yul [Department of Radiation Biology, Environmental Radiation Research Group, Korea Atomic Energy Research Institute, 989-111 Daedeok-daero, Yuseong-gu, Daejeon 305-353 (Korea, Republic of); Cho, Eun-Wie [Epigenomics Research Center, Korea Research Institute of Bioscience and Biotechnology, 125 Gwahak-ro, Yuseong-gu, Daejeon 305-806 (Korea, Republic of)

    2014-11-21

    Highlights: • FBLN-3 gene was poorly expressed in some pancreatic cancer lines. • FBLN-3 promoter region was highly methylated in some pancreatic cancer cell lines. • FBLN-3 inhibited c-MET activation and expression and reduced cellular level of ALDH1. • FBLN-3/c-Met/ALDH1 axis modulates stemness and EMT in pancreatic cancer cells. - Abstract: Fibulin-3 (FBLN-3) has been postulated to be either a tumor suppressor or promoter depending on the cell type, and hypermethylation of the FBLN-3 promoter is often associated with human disease, especially cancer. We report that the promoter region of the FBLN-3 was significantly methylated (>95%) in some pancreatic cancer cell lines and thus FBLN-3 was poorly expressed in pancreatic cancer cell lines such as AsPC-1 and MiaPaCa-2. FBLN-3 overexpression significantly down-regulated the cellular level of c-MET and inhibited hepatocyte growth factor-induced c-MET activation, which were closely associated with γ-radiation resistance of cancer cells. Moreover, we also showed that c-MET suppression or inactivation decreased the cellular level of ALDH1 isozymes (ALDH1A1 or ALDH1A3), which serve as cancer stem cell markers, and subsequently induced inhibition of cell growth in pancreatic cancer cells. Therefore, forced overexpression of FBLN-3 sensitized cells to cytotoxic agents such as γ-radiation and strongly inhibited the stemness and epithelial to mesenchymal transition (EMT) property of pancreatic cancer cells. On the other hand, if FBLN3 was suppressed in FBLN-3-expressing BxPC3 cells, the results were opposite. This study provides the first demonstration that the FBLN-3/c-MET/ALDH1 axis in pancreatic cancer cells partially modulates stemness and EMT as well as sensitization of cells to the detrimental effects of γ-radiation.

  1. Fibulin-3 negatively regulates ALDH1 via c-MET suppression and increases γ-radiation-induced sensitivity in some pancreatic cancer cell lines

    International Nuclear Information System (INIS)

    Kim, In-Gyu; Lee, Jae-Ha; Kim, Seo-Yoen; Kim, Jeong-Yul; Cho, Eun-Wie

    2014-01-01

    Highlights: • FBLN-3 gene was poorly expressed in some pancreatic cancer lines. • FBLN-3 promoter region was highly methylated in some pancreatic cancer cell lines. • FBLN-3 inhibited c-MET activation and expression and reduced cellular level of ALDH1. • FBLN-3/c-Met/ALDH1 axis modulates stemness and EMT in pancreatic cancer cells. - Abstract: Fibulin-3 (FBLN-3) has been postulated to be either a tumor suppressor or promoter depending on the cell type, and hypermethylation of the FBLN-3 promoter is often associated with human disease, especially cancer. We report that the promoter region of the FBLN-3 was significantly methylated (>95%) in some pancreatic cancer cell lines and thus FBLN-3 was poorly expressed in pancreatic cancer cell lines such as AsPC-1 and MiaPaCa-2. FBLN-3 overexpression significantly down-regulated the cellular level of c-MET and inhibited hepatocyte growth factor-induced c-MET activation, which were closely associated with γ-radiation resistance of cancer cells. Moreover, we also showed that c-MET suppression or inactivation decreased the cellular level of ALDH1 isozymes (ALDH1A1 or ALDH1A3), which serve as cancer stem cell markers, and subsequently induced inhibition of cell growth in pancreatic cancer cells. Therefore, forced overexpression of FBLN-3 sensitized cells to cytotoxic agents such as γ-radiation and strongly inhibited the stemness and epithelial to mesenchymal transition (EMT) property of pancreatic cancer cells. On the other hand, if FBLN3 was suppressed in FBLN-3-expressing BxPC3 cells, the results were opposite. This study provides the first demonstration that the FBLN-3/c-MET/ALDH1 axis in pancreatic cancer cells partially modulates stemness and EMT as well as sensitization of cells to the detrimental effects of γ-radiation

  2. Targeting MUC1-C suppresses BCL2A1 in triple-negative breast cancer.

    Science.gov (United States)

    Hiraki, Masayuki; Maeda, Takahiro; Mehrotra, Neha; Jin, Caining; Alam, Maroof; Bouillez, Audrey; Hata, Tsuyoshi; Tagde, Ashujit; Keating, Amy; Kharbanda, Surender; Singh, Harpal; Kufe, Donald

    2018-01-01

    B-cell lymphoma 2-related protein A1 (BCL2A1) is a member of the BCL-2 family of anti-apoptotic proteins that confers resistance to treatment with anti-cancer drugs; however, there are presently no agents that target BCL2A1. The MUC1-C oncoprotein is aberrantly expressed in triple-negative breast cancer (TNBC) cells, induces the epithelial-mesenchymal transition (EMT) and promotes anti-cancer drug resistance. The present study demonstrates that targeting MUC1-C genetically and pharmacologically in TNBC cells results in the downregulation of BCL2A1 expression. The results show that MUC1-C activates the BCL2A1 gene by an NF-κB p65-mediated mechanism, linking this pathway with the induction of EMT. The MCL-1 anti-apoptotic protein is also of importance for the survival of TNBC cells and is an attractive target for drug development. We found that inhibiting MCL-1 with the highly specific MS1 peptide results in the activation of the MUC1-C→NF-κB→BCL2A1 pathway. In addition, selection of TNBC cells for resistance to ABT-737, which inhibits BCL-2, BCL-xL and BCL-W but not MCL-1 or BCL2A1, is associated with the upregulation of MUC1-C and BCL2A1 expression. Targeting MUC1-C in ABT-737-resistant TNBC cells suppresses BCL2A1 and induces death, which is of potential therapeutic importance. These findings indicate that MUC1-C is a target for the treatment of TNBCs unresponsive to agents that inhibit anti-apoptotic members of the BCL-2 family.

  3. Optimization of 90Sr/89Sr measurements

    Directory of Open Access Journals (Sweden)

    Legarda F.

    2012-04-01

    Full Text Available One of the key points in the double measurement method for the measurement of both, 89Sr and 90Sr, by using a proportional counter is the choice of the times at which the measurements should be done. In this paper, the formulae to calculate the 89Sr and 90Sr detection limits in conditions of radioactive equilibrium between 90Y and 90Sr are derived, and an analysis of them as a function of the time between the two measurements is done. The choice for the time of the second measurement is going to depend on the desired quality of the results to be obtained.

  4. An analysis of content in comprehensive cancer control plans that address chronic hepatitis B and C virus infections as major risk factors for liver cancer.

    Science.gov (United States)

    Momin, Behnoosh; Richardson, Lisa

    2012-08-01

    Chronic hepatitis B and hepatitis C virus (HBV and HCV) infections are among the leading causes of preventable death worldwide. Chronic viral hepatitis is the cause of most primary liver cancer, which is the third leading cause of cancer deaths globally and the ninth leading cause of cancer deaths in the United States. The extent to which comprehensive cancer control (CCC) programs in states, tribal governments and organizations, territories, and Pacific Island jurisdictions address chronic hepatitis B and/or hepatitis C infections as risk factors for liver cancer or recommend interventions for liver cancer prevention in their CCC plans remains unknown. We searched CCC plans for this information using the search tool at http://www.cdc.gov/cancer/ncccp/ to access the content of plans for this information. A combination of key search terms including "liver cancer", "hepatitis", "chronic alcohol", and "alcohol abuse" were used to identify potential content regarding liver cancer risk factors and prevention. Relevant content was abstracted for further review and classification. Of 66 (Although CDC funds 65 programs, one of the Pacific Island Jurisdiction grantees is the Federated States of Micronesia (FSM). This national program supports four FSM states, each of which submits a cancer plan to CDC for a total of 69 plans. During this time period, 66 plans were available on the website.) CCC plans, 27% (n = 18) addressed liver cancer using the above-mentioned search terms. In the 23 plans that addressed HBV and/or HCV, there were 25 goals, objectives, strategies, and outcomes aimed at reducing the incidence or prevalence of HBV and/or HCV infection. While nearly a third of CCC programs identify at least one goal, objective, strategy, outcome, or prevention program to reduce cancer burden in their CCC plans, few plans discuss specific actions needed to reduce the burden of liver cancer.

  5. TOKSISITAS PROTEIN 89 kDa PRODUK EKSTRASELULER Streptococcus agalactiae PADA IKAN NILA (Oreochromis niloticus

    Directory of Open Access Journals (Sweden)

    Amrullah Amrullah

    2015-09-01

    Full Text Available Identifikasi protein toksin yang bersifat antigenik dari produk ekstraselular (ECP crude Streptococcus agalactiae penting dilakukan untuk pengembangan vaksin protein toksoid. Penelitian ini bertujuan untuk mengevaluasi toksisitas protein dengan berat molekul 89 kDa dari ECP Streptococcus agalactiae hasil fraksinasi dengan SDS-PAGE (ECPP89. Ikan nila dengan bobot sekitar 25 g masing-masing diinjeksi secara intraperitonial dengan protein ECPP89 dosis 1, 2, 4, 8, dan 16 μg/mL/ekor ikan (secara berturut-turut diberi kode ECPP89-1, ECPP89-2, ECPP89-4, ECPP89-8, dan ECPP89-16. Sebagai kontrol positif ikan diinjeksi dengan bakteri utuh S. agalactiae 1 x 104 cfu/mL (WCB dan ECP crude S. agalactiae (ECPC, sementara kontrol negatif ikan diinjeksi larutan PBS. Ikan dipelihara selama 15 hari dengan kepadatan 10 ekor (70 L air. Hasil penelitian menunjukkan bahwa ikan nila yang diinjeksi dengan ECPP89 mengalami gejala seperti perubahan morfologi, perubahan nafsu makan, dan perubahan renang ikan. Mortalitas pada perlakuan ECPP89 secara umum lebih tinggi dibandingkan dengan ECPC, namun lebih rendah (p<0,05 dibandingkan dengan WCB. Mortalitas ikan pada perlakuan ECPP89-4, ECPP89-8, dan ECPP89-16 tidak berbeda tetapi secara signifikan lebih tinggi dibandingkan dengan ECPC dan dua dosis perlakuan ECPP89 lainnya (p<0,05. Ikan kontrol negatif tidak mengalami kematian maupun perubahan klinis. Hasil ini menunjukkan bahwa ECPP89 merupakan protein toksin dari ECP S. agalactiae.

  6. Enhancement of radiotherapy efficacy by miR-200c-loaded gelatinase-stimuli PEG-Pep-PCL nanoparticles in gastric cancer cells

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    Cui FB

    2014-05-01

    Full Text Available Fang-bo Cui,1,* Qin Liu,1,* Ru-Tian Li,1 Jie Shen,1 Pu-yuan Wu,1 Li-Xia Yu,1 Wen-jing Hu,1 Feng-lei Wu,2 Chun-Ping Jiang,1 Guo-feng Yue,2 Xiao-Ping Qian,1 Xi-Qun Jiang,3 Bao-Rui Liu11The Comprehensive Cancer Center of Drum-Tower Hospital, Medical School of Nanjing University and Clinical Cancer Institute of Nanjing University, Nanjing, 2Nanjing Medical University, 3Laboratory of Mesoscopic Chemistry and Department of Polymer Science and Engineering, College of Chemistry and Chemical Engineering, Nanjing University, Nanjing, People's Republic of China*These authors contributed equally to this workAbstract: Radiotherapy is the main locoregional control modality for many types of unresectable tumors, including gastric cancer. However, many patients fail radiotherapy due to intrinsic radioresistance of cancer cells, which has been found to be strongly associated with cancer stem cell (CSC-like properties. In this study, we developed a nanoparticle formulation to deliver miR-200c, which is reported to inhibit CSC-like properties, and then evaluated its potential activity as a radiosensitizer. miR-200c nanoparticles significantly augmented radiosensitivity in three gastric cancer cell lines (sensitization enhancement ratio 1.13–1.25, but only slightly in GES-1 cells (1.06. In addition to radioenhancement, miR-200c nanoparticles reduced the expression of CD44, a putative CSC marker, and the percentage of CD44+ BGC823 cells. Meanwhile, other CSC-like properties, including invasiveness and resistance to apoptosis, could be suppressed by miR-200c nanoparticles. CSC-associated radioresistance mechanisms, involving reactive oxygen species levels and DNA repair capacity, were also attenuated. We have demonstrated that miR-200c nanoparticles are an effective radiosensitizer in gastric cancer cells and induce little radiosensitization in normal cells, which suggests that they are as a promising candidate for further preclinical and clinical evaluation

  7. Desorption of Sr 89, Co 60 and Cs 134 from Suez Canal bottom sediments (Port Tawfeek Area)

    International Nuclear Information System (INIS)

    El-Assy, N.B.; Abdel-Fattah, A.T.; El-Shinawy, R.M.K.; Essa, M.W.A.

    1986-01-01

    Chemical and physical properties of Suez Canal Bottom Sediments (S.C.B.S) and seawater at Port Tawfeek, the south entrance of Suez Canal, were studied. The (S.C.B.S) was separated into its size fractions (natural sediment, sand, silt and clay). These different sediment fractions were allowed to be in equilibrium with Strontium 89, Cobalt 60 and Cesium 134 solutions. Desorption studies were carried out on these contaminated sediments. The release of Strontium 89 and Cesium 134 was found to be identical and the sequence of this release was as follows : sand> silt> natural sediment> clay. The effect of seawater is 6-8 times that of bidistilled water. In case of Cobalt 60 the above sequence was disturbed and the salinity effect was only 2 times that of bidistilled water. It was also found that Strontium and Cobalt were more easily desorbed from the sand fraction a behaviour which can be explained by their loose attachment to the crystal surface

  8. The prevalence of deranged C-reactive protein and albumin in patients with incurable cancer approaching death.

    Science.gov (United States)

    Gray, Sarah; Axelsson, Bertil

    2018-01-01

    Amongst patients with incurable cancer approaching death, cachexia is common and associated with adverse outcomes. The term cachexia lacks a universally accepted definition and there is no consensus regarding which variables are to be measured. Furthermore, an elevated C-reactive protein is a common clinical challenge in this patient group. This study aims to add to the ongoing discussion regarding the definition of cancer cachexia and to study the role of C-reactive protein and s-albumin in this context. A 1-year cohort, consisting of 155 cancer patients enrolled in a specialized palliative home care team in the city of Östersund, Sweden, that were deceased during the year of 2015 was studied. Laboratory measures were studied within 0-30 and 31-60 days prior to death. C-reactive protein >10 mg/L and coinciding s-albumin death was noted. The prevalence of "laboratory cachexia" was 85% 0-30 days prior to death compared to 66% 31-60 days prior to death (pdeath, with a median of 47 days. The median values for C-reactive protein and s-albumin within 0-30 days prior to death were 84mg/L and 23g/L respectively. Could markedly deranged values of C-reactive protein and s-albumin, such as found in this study, signal a relatively short remaining survival time in patients with incurable cancer and no clinical signs of ongoing infection? The role of "laboratory cachexia" in this context as well as the cut off values for the laboratory measures included may be further discussed.

  9. Mapping of Powdery Mildew Resistance Gene pmCH89 in a Putative Wheat-Thinopyrum intermedium Introgression Line

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    Liyuan Hou

    2015-07-01

    Full Text Available Powdery mildew, caused by Blumeria graminis f. sp. tritici (Bgt, is a globally serious disease adversely affecting wheat production. The Bgt-resistant wheat breeding line CH09W89 was derived after backcrossing a Bgt resistant wheat-Thinopyrum intermedium partial amphiploid TAI7045 with susceptible wheat cultivars. At the seedling stage, CH09W89 exhibited immunity or high resistance to Bgt pathotypes E09, E20, E21, E23, E26, Bg1, and Bg2, similar to its donor line TAI7045 and Th. intermedium. No Th. intermedium chromatin was detected based on genomic in situ hybridization of mitotic chromosomes. To determine the mode of inheritance of the Bgt resistance and the chromosomal location of the resistance gene, CH09W89 was crossed with two susceptible wheat cultivars. The results of the genetic analysis showed that the adult resistance to Bgt E09 in CH09W89 was controlled by a single recessive gene, which was tentatively designated as pmCH89. Two polymorphic SSR markers, Xwmc310 and Xwmc125, were linked to the resistance gene with genetic distances 3.1 and 2.7 cM, respectively. Using the Chinese Spring aneuploid and deletion lines, the resistance gene and its linked markers were assigned to chromosome arm 4BL in the bin 0.68–0.78. Due to its unique position on chromosome 4BL, pmCH89 appears to be a new locus for resistance to powdery mildew. These results will be of benefit for improving powdery mildew resistance in wheat breeding programs.

  10. Conserved features of cancer cells define their sensitivity to HAMLET-induced death; c-Myc and glycolysis.

    Science.gov (United States)

    Storm, P; Aits, S; Puthia, M K; Urbano, A; Northen, T; Powers, S; Bowen, B; Chao, Y; Reindl, W; Lee, D Y; Sullivan, N L; Zhang, J; Trulsson, M; Yang, H; Watson, J D; Svanborg, C

    2011-12-01

    HAMLET is the first member of a new family of tumoricidal protein-lipid complexes that kill cancer cells broadly, while sparing healthy, differentiated cells. Many and diverse tumor cell types are sensitive to the lethal effect, suggesting that HAMLET identifies and activates conserved death pathways in cancer cells. Here, we investigated the molecular basis for the difference in sensitivity between cancer cells and healthy cells. Using a combination of small-hairpin RNA (shRNA) inhibition, proteomic and metabolomic technology, we identified the c-Myc oncogene as one essential determinant of HAMLET sensitivity. Increased c-Myc expression levels promoted sensitivity to HAMLET and shRNA knockdown of c-Myc suppressed the lethal response, suggesting that oncogenic transformation with c-Myc creates a HAMLET-sensitive phenotype. Furthermore, HAMLET sensitivity was modified by the glycolytic state of tumor cells. Glucose deprivation sensitized tumor cells to HAMLET-induced cell death and in the shRNA screen, hexokinase 1 (HK1), 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 1 and hypoxia-inducible factor 1α modified HAMLET sensitivity. HK1 was shown to bind HAMLET in a protein array containing ∼8000 targets, and HK activity decreased within 15 min of HAMLET treatment, before morphological signs of tumor cell death. In parallel, HAMLET triggered rapid metabolic paralysis in carcinoma cells. Tumor cells were also shown to contain large amounts of oleic acid and its derivatives already after 15 min. The results identify HAMLET as a novel anti-cancer agent that kills tumor cells by exploiting unifying features of cancer cells such as oncogene addiction or the Warburg effect.

  11. Conserved features of cancer cells define their sensitivity of HAMLET-induced death; c-Myc and glycolysis

    Science.gov (United States)

    Storm, Petter; Puthia, Manoj Kumar; Aits, Sonja; Urbano, Alexander; Northen, Trent; Powers, Scott; Bowen, Ben; Chao, Yinxia; Reindl, Wolfgang; Lee, Do Yup; Sullivan, Nancy Liu; Zhang, Jianping; Trulsson, Maria; Yang, Henry; Watson, James; Svanborg, Catharina

    2014-01-01

    HAMLET is the first member of a new family of tumoricidal protein-lipid complexes that kill cancer cells broadly, while sparing healthy, differentiated cells. Many and diverse tumor cell types are sensitive to the lethal effect, suggesting that HAMLET identifies and activates conserved death pathways in cancer cells. Here we investigated the molecular basis for the difference in sensitivity between cancer cells and healthy cells. Using a combination of small hairpin RNA inhibition, proteomic and metabolomic technology we identified the c-Myc oncogene as one essential determinant of HAMLET sensitivity. Increased c-Myc expression levels promoted the sensitivity to HAMLET and shRNA knockdown of c-Myc suppressed the lethal response, suggesting that oncogenic transformation with c-Myc creates a HAMLET-sensitive phenotype. Furthermore, the HAMLET sensitivity was modified by the glycolytic state of the tumor cells. Glucose deprivation sensitized tumor cells to HAMLET-induced cell death and in the shRNA screen Hexokinase 1, PFKFB1 and HIF1α modified HAMLET sensitivity. Hexokinase 1 was shown to bind HAMLET in a protein array containing approximately 8000 targets and Hexokinase activity decreased within 15 minutes of HAMLET treatment, prior to morphological signs of tumor cell death. In parallel, HAMLET triggered rapid metabolic paralysis in carcinoma cells. The glycolytic machinery was modified and glycolysis was shifted towards the pentose phosphate pathway. Tumor cells were also shown to contain large amounts of oleic acid and its derivatives already after 15 minutes. The results identify HAMLET as a novel anti-cancer agent that kills tumor cells by exploiting unifying features of cancer cells such as oncogene-addiction or the Warburg effect. PMID:21643007

  12. 3',5'-Cyclic diguanylic acid (c-di-GMP) inhibits basal and growth factor-stimulated human colon cancer cell proliferation

    International Nuclear Information System (INIS)

    Karaolis, David K.R.; Cheng, Kunrong; Lipsky, Michael; Elnabawi, Ahmed; Catalano, Jennifer; Hyodo, Mamoru; Hayakawa, Yoshihiro; Raufman, Jean-Pierre

    2005-01-01

    The novel cyclic dinucleotide, 3',5'-cyclic diguanylic acid, cGpGp (c-di-GMP), is a naturally occurring small molecule that regulates important signaling mechanisms in prokaryotes. Recently, we showed that c-di-GMP has 'drug-like' properties and that c-di-GMP treatment might be a useful antimicrobial approach to attenuate the virulence and pathogenesis of Staphylococcus aureus and prevent or treat infection. In the present communication, we report that c-di-GMP (≤50 μM) has striking properties regarding inhibition of cancer cell proliferation in vitro. c-di-GMP inhibits both basal and growth factor (acetylcholine and epidermal growth factor)-induced cell proliferation of human colon cancer (H508) cells. Toxicity studies revealed that exposure of normal rat kidney cells and human neuroblastoma cells to c-di-GMP at biologically relevant doses showed no lethal cytotoxicity. Cyclic dinucleotides, such as c-di-GMP, represent an attractive and novel 'drug-platform technology' that can be used not only to develop new antimicrobial agents, but also to develop novel therapeutic agents to prevent or treat cancer

  13. Consistent expression of guanylyl cyclase-C in primary and metastatic gastrointestinal cancers.

    Directory of Open Access Journals (Sweden)

    Hadi Danaee

    Full Text Available The transmembrane receptor guanylate cyclase-C (GCC has been found to be expressed in colorectal cancers. However, limited data are available on GCC protein expression in non-colorectal gastrointestinal tumors and few studies have reported whether GCC protein expression was consistently preserved in synchronous primary and metastatic cancer tissues.GCC protein status was assessed by immunohistochemistry in tumor specimens from individuals (n = 627 with gastrointestinal tumors, including esophageal (n = 130, gastric (n = 276, pancreatic (n = 136, and colorectal (n = 85 primary and metastatic tumors. Tissue specimens consisted of tissue microarrays containing esophageal, gastric, pancreatic tumors, and whole-slide tissue sections from colorectal cancer patients with matching primary and metastatic tumors.Among the evaluated esophageal, gastric, and pancreatic tumors, the frequency of GCC positivity at the protein level ranged from 59% to 68%. GCC was consistently expressed in primary and matched/synchronous metastatic lesions of colorectal cancer tissues derived from the same patients.This observational study demonstrated the protein expression of GCC across various gastrointestinal malignancies. In all cancer histotypes, GCC protein localization was observed predominantly in the cytoplasm compared to the membrane region of tumor cells. Consistent immunohistochemistry detection of GCC protein expression in primary colorectal cancers and in their matched liver metastases suggests that the expression of GCC is maintained throughout the process of tumor progression and formation of metastatic disease.

  14. Synsepalum dulcificum extracts exhibit cytotoxic activity on human colorectal cancer cells and upregulate c-fos and c-jun early apoptotic gene expression

    Directory of Open Access Journals (Sweden)

    Jichang Seong

    2018-01-01

    Full Text Available Objective: To explore cytotoxicity of Synsepalum dulcificum (S. dulcificum Daniell (Sapotaceae on human colon cancer (HCT-116 and HT-29, human monocytic leukemia (THP-1 and normal (HDFn cell lines, and its effect on the expression of early apoptotic genes, c-fos and c-jun. Methods: Leaf, stem and berry of S. dulcificum were separately extracted by using 2 solvents, 10% ethanol (EtOH and 80% methanol (MeOH. PrestoBlue® cell viability assay and qRT-PCR assay were conducted to examine the above objectives respectively. Results: Stem MeOH, stem EtOH, and berry EtOH extracts of S. dulcificum were cytotoxic to HCT-116 and HT-29 human colon cancer cells. For HCT-116, IC50 values of these 3 extracts were not significantly different (P>0.05 from that of the positive control bleomycin (IC50 of 33.57 μg/mL, while for HT-29, IC50 values of these 3 extracts were significantly lower (P<0.05 than that of bleomycin (IC50 of 25.24 μg/mL. None of the extracts were cytotoxic to the THP-1 monocytic leukemia cells and HDFn normal human dermal fibroblasts. For both HCT-116 and HT-29, these extracts significantly up-regulated (P<0.05 the expression of c-fos and c-jun compared to the untreated negative control. Conclusions: The results of this study suggest that cytotoxicity of stem MeOH, stem EtOH, and berry EtOH extracts of S. dulcificum on HCT-116 and HT-29 colon cancer cells is due to the induced apoptosis which is caused by the up-regulation of the expression of early apoptotic genes, c-fos and c-jun.

  15. Exploratory study of long-term health-related quality of life in patients with surgically treated primary parotid gland cancer.

    Science.gov (United States)

    Stenner, Markus; Beenen, Franziska; Hahn, Moritz; Koopmann, Mario; Weiss, Daniel; Hüttenbrink, Karl-Bernd

    2016-01-01

    Health-related quality of life (HRQOL) has received more and more attention as an outcome in cancer therapy. In this exploratory study, we assessed the long-term HRQOL among 77 surgically treated patients with parotid gland cancer. The European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30-questions (EORTC-QLQ-C30) and European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 Head and Neck 35-questions (EORTC-QLQ-C30-H&N35) questionnaires were used in a cross-sectional design. The mean time-lag between initial diagnosis and completion of the questionnaire was 89.7 months. The HRQOL significantly increased with the time-lag to surgery and decreased with the patients' age. Factors with clinically significant effects in several areas of long-term HRQOL (ie, more than 4 scores) were age, type of neck dissection, preoperative facial nerve palsy, and postoperative radiation therapy. In parotid gland cancer surgery, factors, such as sex, age, type of surgery, facial nerve palsy, and radiation therapy, seem to be associated with clinically meaningful differences in long-term HRQOL scores. © 2015 Wiley Periodicals, Inc.

  16. Functional inhibition of Ubiquitin conjugating Enzyme (UBE2C) reduces proliferation and sensitizes cervical and breast cancer cells to radiation, doxorubicin, tamoxifen and letrozole

    International Nuclear Information System (INIS)

    Bose, Mayil Vahanan; Rawat, Akhilesh; Gopisetty, Gopal; Thangarajan, Rajkumar; Ganesharaja, Selvaluxmy

    2014-01-01

    Cervical cancer is the second most common cancer in women, worldwide. About 80% of cervical cancer cases occur in developing countries. Breast cancer has overtaken cervical cancer in most of the urban centers in India. In recent years, interest in the role of Ubiquitin conjugating Enzyme E2C (UBE2C) in cancer has shown a dramatic increase. Several studies have reported UBE2C as a potential oncogene and therapeutic target. The objective of the study was to elucidate radiation and chemo-sensitivity in response to functional inhibition of UBE2C in cervical and breast cancer cell lines. Taqman Real time PCR was performed to measure UBE2C levels in cervical and breast cancer cell lines. A dominant negative form of UBE2C (DN-UBE2C) was used to functionally inhibit wild type UBE2C. Cell proliferation and anchorage independent growth were measured by colorimetric assay and soft agar assay respectively. Radiation and chemo response of cell lines were assessed by colorimetric assay and clonogenic assay. Difference in sensitivity to radiation was observed among the cervical cancer cell lines studied. The growth rate of SiHa and HeLa transfected with DN- UBE2C was significantly reduced compared to vector control. Further, DN-UBE2C mediated radio-sensitivity was correlated with a significant decrease in resistance to radiation by SiHa and HeLa cells after transfection when compared to control cultures. Similarly, both the growth rate and the anchorage independent growth of MCF7 and MDAMB231 cells transfected with DN-UBE2C were significantly reduced compared to cells transfected with vector alone. MCF7 and MDAMB231 cells expressing DN-UBE2C were significantly more sensitive to different doses of radiation and doxorubicin compared to controls. In addition, DN-UBE2C transfected MCF7 cells were more sensitive to inhibition by tamoxifen and letrozole compared to vector controls. These results suggest that UBE2C can be used as a potential therapeutic target for cervical and breast

  17. Improved production and processing of 89Zr using a solution target

    International Nuclear Information System (INIS)

    Pandey, Mukesh K.; Bansal, Aditya; Engelbrecht, Hendrik P.; Byrne, John F.; Packard, Alan B.; DeGrado, Timothy R.

    2016-01-01

    Objective: The objectives of the present work were to improve the cyclotron production yield of 89 Zr using a solution target, develop a practical synthesis of the hydroxamate resin used to process the target, and develop a biocompatible medium for 89 Zr elution from the hydroxamate resin. Methods: A new solution target (BMLT-2) with enhanced heat dissipation capabilities was designed by using helium-cooled dual foils (0.2 mm Al and 25 μ Havar) and an enhanced water-cooled, elongated solution cavity in the target insert. Irradiations were performed with 14 MeV protons on a 2 M solution of yttrium nitrate in 1.25 M nitric acid at 40-μA beam current for 2 h in a closed system. Zirconium-89 was separated from Y by use of a hydroxamate resin. A one-pot synthesis of hydroxamate resin was accomplished by activating the carboxylate groups on a carboxymethyl cation exchange resin using methyl chloroformate followed by reaction with hydroxylamine hydrochloride. After trapping of 89 Zr on hydroxamate resin and rinsing the resin with HCl and water to release Y, 89 Zr was eluted with 1.2 M K 2 HPO 4 /KH 2 PO 4 buffer (pH 3.5). ICP-MS was used to measure metal contaminants in the final 89 Zr solution. Results: The BMLT-2 target produced 349 ± 49 MBq (9.4 ± 1.2 mCi) of 89 Zr at the end of irradiation with a specific activity of 1.18 ± 0.79 GBq/μg. The hydroxamate resin prepared using the new synthesis method showed a trapping efficiency of 93% with a 75 mg resin bed and 96–97% with a 100–120 mg resin bed. The elution efficiency of 89 Zr with 1.2 M K 2 HPO 4 /KH 2 PO 4 solution was found to be 91.7 ± 3.7%, compared to > 95% for 1 M oxalic acid. Elution with phosphate buffer gave very small levels of metal contaminants: Al = 0.40–0.86 μg (n = 2), Fe = 1.22 ± 0.71 μg (n = 3), Y = 0.29 μg (n = 1). Conclusions: The BMLT-2 target allowed doubling of the beam current for production of 89 Zr, resulting in a greater than 2-fold increase in production yield in comparison

  18. [C677T-SNP of methylenetetrahydrofolate reductase gene and breast cancer in Mexican women].

    Science.gov (United States)

    Calderón-Garcidueñas, Ana Laura; Cerda-Flores, Ricardo Martín; Castruita-Ávila, Ana Lilia; González-Guerrero, Juan Francisco; Barrera-Saldaña, Hugo Alberto

    2017-01-01

    Low-penetrance susceptibility genes such as 5,10-methylenetetrahydrofolate reductase gene (MTHFR) have been considered in the progression of breast cancer (BC). Cancer is a result of genetic, environmental and epigenetic interactions; therefore, these genes should be studied in environmental context, because the results can vary between populations and even within the same country. The objective was to analyze the allelic and genotypic frequencies of the MTHFR C667T SNP in Mexican Mestizo patients with BC and controls from Northeastern Mexico. 243 patients and 118 healthy women were studied. The analysis of the polymorphism was performed with a DNA microarray. Once the frequency of the polymorphism was obtained, Hardy-Weinberg equilibrium test was carried out for the genotypes. Chi square test was used to compare the distribution of frequencies. The allele frequency in patients was: C = 0.5406; T = 0.4594 and in controls C = 0.5678, T = 0.4322. Genotype in BC patients was: C / C = 29.9%, C / T = 48.3% and T / T = 21.8. The distribution in controls was: C / C = 31.4%, C / T = 50.8%, T / T = 17.8% (chi squared 0.77, p = 0.6801). Northeastern Mexican women in this study showed no association between MTFHR C667T SNP and the risk of BC. It seems that the contribution of this polymorphism to BC in Mexico varies depending on various factors, both genetic and environmental.

  19. SU-E-I-82: PET Radiopharmaceuticals for Prostate Cancer Imaging: A Review

    Energy Technology Data Exchange (ETDEWEB)

    Fernandes, F [Delfin Farmacos e Derivados Ltda, Lauro De Freitas, Bahia (Brazil); Escola Bahiana de Medicina e Saude Publica, Salvador, Bahia (Brazil); Silva, D da [Delfin Farmacos e Derivados Ltda, Lauro De Freitas, Bahia (Brazil); Rodrigues, L [Escola Bahiana de Medicina e Saude Publica, Salvador, Bahia (Brazil)

    2015-06-15

    Purpose: The aim of this work was to review new and clinical practice PET radiopharmaceuticals for prostate cancer imaging. Methods: PET radiopharmaceuticals were reviewed on the main databases. Availability, dosimetry, accuracy and limitations were considered. Results: The following radioisotopes with respective physical half-life and mean positron energy were found: {sup 18}F (109,7 min, 249,8 keV), {sup 89}Zr (78,4 hs, 395,5 keV), {sup 11}C (20,4 min, 385,7 keV) and {sup 68}Ga (67,8 min, 836 keV). {sup 68}Ga was the only one not produced by cyclotron. Radiopharmaceuticals uptake by glucose metabolism ({sup 18}F-FDG), lipogenesis ({sup 11}C-Choline and {sup 11}C-Acetate), amino acid transport (Anti-{sup 18}F-FACBC), bone matrix ({sup 18}F-NaF), prostatespecific membrane antigen ({sup 68}Ga-PSMA and {sup 89}Zr-J591), CXCR receptors ({sup 89}Ga-Pentixafor), adrenal receptors ({sup 18}F-FDHT) and gastrin release peptide receptor (bombesin analogue). Most of radiopharmaceuticals are urinary excretion, so bladder is the critical organ. 11C-choline (pancreas), Anti-{sup 18}FFACBC (liver) and {sup 18}F-FBDC (stomach wall) are the exception. Higher effective dose was seen {sup 18}F-NaF (27 μSv/MBq) while the lowest was {sup 11}CAcetate (3,5 μSv/MBq). Conclusion: Even though {sup 18}F-FDG has a large availability its high urinary excretion and poor uptake to slow growing disease offers weak results for prostate cancer. Better accuracy is obtained when {sup 18}F-NaF is used for bone metastatic investigation although physicians tend to choose bone scintigraphy probably due to its cost and practice. Many guidelines in oncology consider {sup 11}C or {sup 18}F labeled with Choline the gold standard for biochemical relapse after radical treatment. Local, lymph node and distant metastatic relapse can be evaluated at same time with this radiopharmaceutical. There is no consensus over bigger urinary excretion for {sup 18}F labeling. Anti-{sup 18}F-FACBC, {sup 68}Ga-PSMA and {sup

  20. Fully microscopic DWBA analyses on 89Y (α, p)92Zr reaction

    International Nuclear Information System (INIS)

    Yuan Jian; Mao Zhiqiang; Zhang Peihua

    1988-01-01

    The differential cross sections have been measured for the 89 Y (α, p) 92 Zr reaction with some low-lying states and the 89 Y (α, α) 8( Y elastic scattering by using 26.1 MeV α beam. A fully microscopic DWBA analyses for 89 Y (α, α) 92 Zr have been performed by using 89 Y and 92 Zr shell-model wavefunction with or without the core excited configuration. With the core excited configuration, relative strengths of the ground state and the first excited state are greatly improved. Finally, the absolute cross sections for 89 (α, p) 92 Zr and importance of shallow well depth of α potential are discussed

  1. Gene therapy for C-26 colon cancer using heparin-polyethyleneimine nanoparticle-mediated survivin T34A

    Directory of Open Access Journals (Sweden)

    Zhang L

    2011-10-01

    Full Text Available Ling Zhang1,*, Xiang Gao1,2,*, Ke Men1, BiLan Wang1, Shuang Zhang1, Jinfeng Qiu1, Meijuan Huang1, MaLing Gou1, Ning Huang2, ZhiYong Qian1, Xia Zhao1, YuQuan Wei11State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, West China Medical School, 2Department of Pathophysiology, College of Preclinical and Forensic Medical Sciences, Sichuan University, Chengdu, People’s Republic of China*These authors contributed equally to this workBackground: Gene therapy provides a novel method for the prevention and treatment of cancer, but the clinical application of gene therapy is restricted, mainly because of the absence of an efficient and safe gene delivery system. Recently, we developed a novel nonviral gene carrier, ie, heparin-polyethyleneimine (HPEI nanoparticles for this purpose.Methods and results: HPEI nanoparticles were used to deliver plasmid-expressing mouse survivin-T34A (ms-T34A to treat C-26 carcinoma in vitro and in vivo. According to the in vitro studies, HPEI nanoparticles could efficiently transfect the pGFP report gene into C-26 cells, with a transfection efficiency of 30.5% ± 2%. Moreover, HPEI nanoparticle-mediated ms-T34A could efficiently inhibit the proliferation of C-26 cells by induction of apoptosis in vitro. Based on the in vivo studies, HPEI nanoparticles could transfect the Lac-Z report gene into C-26 cells in vivo. Intratumoral injection of HPEI nanoparticle-mediated ms-T34A significantly inhibited growth of subcutaneous C-26 carcinoma in vivo by induction of apoptosis and inhibition of angiogenesis.Conclusion: This research suggests that HPEI nanoparticle-mediated ms-T34A may have a promising role in C-26 colon carcinoma therapy.Keywords: gene therapy, mouse survivin-T34A, colon cancer, polyethyleneimine, nanoparticles, cancer therapy

  2. The importance of -460 C/T and +405 G/C single nucleotide polymorphisms to the function of vascular endothelial growth factor A in colorectal cancer

    DEFF Research Database (Denmark)

    Hansen, Torben F; Spindler, Karen-Lise G; Lorentzen, Karen A

    2010-01-01

    collected from 113 patients surgically resected for colorectal cancer. SNPs were analysed from genomic DNA by PCR, the VEGF-A gene expression analysis was performed by RT-PCR and protein analysis by ELISA. RESULTS: The T-allele in the -460 C/T SNP and the C-allele in the +405 G/C SNP were associated...... with significantly lower VEGF-A protein levels in normal colorectal tissue. There were no differences in protein levels in the malignant tissue according to genotypes. No differences were observed at the gene expression levels either. CONCLUSION: The results indicate that the two SNPs have a functional influence......PURPOSE: The present study investigated the functional influence of the single nucleotide polymorphisms (SNPs) -460 C/T and +405 G/C at vascular endothelial growth factor A (VEGF-A), mRNA and protein levels in colorectal cancer (CRC) and normal colorectal tissue. METHODS: Blood and tissue were...

  3. A Study Of Oral PF-02341066, A C-Met/Hepatocyte Growth Factor Tyrosine Kinase Inhibitor, In Patients With Advanced Cancer

    Science.gov (United States)

    2018-01-29

    Non-Small Cell Lung Cancer ALK-positive; Non-Small Cell Lung Cancer c-Met Dependent; Non-Small Cell Lung Cancer ROS Marker Positive; Systemic Anaplastic Large-Cell Lymphoma; Advanced Malignancies Except Leukemia

  4. Vascular endothelial growth factor C promotes cervical cancer metastasis via up-regulation and activation of RhoA/ROCK-2/moesin cascade

    International Nuclear Information System (INIS)

    He, Mian; Cheng, Yang; Li, Wen; Liu, Qiongshan; Liu, Junxiu; Huang, Jinghe; Fu, Xiaodong

    2010-01-01

    The elevated expression of vascular endothelial growth factor C (VEGF-C) is correlated with clinical cervical cancer metastasis and patient survival, which is interpreted by VEGF-C functions to stimulate angiogenesis and lymphatic genesis. However, the direct impact of VEGF-C on cervical cancer cell motility remains largely unknown. In this study, we investigated the effects of VEGF-C on actin cytoskeleton remodeling and on cervical cancer cell migration and invasion and how the actin-regulatory protein, moesin regulated these effects through RhoA/ROCK-2 signaling pathway. On cervical carcinoma cell line SiHa cells, exposure of VEGF-C triggered remodeling of the actin cytoskeleton and the formation of membrane ruffles, which was required for cell movement. VEGF-C significantly enhanced SiHa cells horizontal migration and three-dimensional invasion into matrices. These actions were dependent on increased expression and phosphorylation of the actin-regulatory protein moesin and specific moesin siRNA severely impaired VEGF-C stimulated-cell migration. The extracellular small GTPase RhoA/ROCK-2 cascade mediated the increased moesin expression and phosphorylation, which was discovered by the use of Y-27632, a specific inhibitor of Rho kinase and by transfected constitutively active, dominant-negative RhoA as well as ROCK-2 SiRNA. Furthermore, in the surgical cervical specimen from the patients with FIGO stage at cervical intra-epithelial neoplasia and I-II cervical squamous cell carcinoma, the expression levels of moesin were found to be significantly correlated with tumor malignancy and metastasis. These results implied that VEGF-C promoted cervical cancer metastasis by upregulation and activation of moesin protein through RhoA/ROCK-2 pathway. Our findings offer new insight into the role of VEGF-C on cervical cancer progression and may provide potential targets for cervical cancer therapy

  5. Vascular endothelial growth factor C promotes cervical cancer metastasis via up-regulation and activation of RhoA/ROCK-2/moesin cascade

    Directory of Open Access Journals (Sweden)

    Huang Jinghe

    2010-04-01

    Full Text Available Abstract Background The elevated expression of vascular endothelial growth factor C (VEGF-C is correlated with clinical cervical cancer metastasis and patient survival, which is interpreted by VEGF-C functions to stimulate angiogenesis and lymphatic genesis. However, the direct impact of VEGF-C on cervical cancer cell motility remains largely unknown. Methods In this study, we investigated the effects of VEGF-C on actin cytoskeleton remodeling and on cervical cancer cell migration and invasion and how the actin-regulatory protein, moesin regulated these effects through RhoA/ROCK-2 signaling pathway. Results On cervical carcinoma cell line SiHa cells, exposure of VEGF-C triggered remodeling of the actin cytoskeleton and the formation of membrane ruffles, which was required for cell movement. VEGF-C significantly enhanced SiHa cells horizontal migration and three-dimensional invasion into matrices. These actions were dependent on increased expression and phosphorylation of the actin-regulatory protein moesin and specific moesin siRNA severely impaired VEGF-C stimulated-cell migration. The extracellular small GTPase RhoA/ROCK-2 cascade mediated the increased moesin expression and phosphorylation, which was discovered by the use of Y-27632, a specific inhibitor of Rho kinase and by transfected constitutively active, dominant-negative RhoA as well as ROCK-2 SiRNA. Furthermore, in the surgical cervical specimen from the patients with FIGO stage at cervical intra-epithelial neoplasia and I-II cervical squamous cell carcinoma, the expression levels of moesin were found to be significantly correlated with tumor malignancy and metastasis. Conclusions These results implied that VEGF-C promoted cervical cancer metastasis by upregulation and activation of moesin protein through RhoA/ROCK-2 pathway. Our findings offer new insight into the role of VEGF-C on cervical cancer progression and may provide potential targets for cervical cancer therapy.

  6. Effects of cIAP-1, cIAP-2 and XIAP triple knockdown on prostate cancer cell susceptibility to apoptosis, cell survival and proliferation.

    LENUS (Irish Health Repository)

    Gill, Catherine

    2009-01-01

    BACKGROUND: Manipulating apoptotic resistance represents an important strategy for the treatment of hormone refractory prostate cancer. We hypothesised that the Inhibitor of Apoptosis (IAP) Proteins may be mediating this resistance and knockdown of cIAP-1, cIAP-2 and XIAP would increase sensitivity to apoptosis. METHODS: cIAP-1, cIAP-2 and XIAP where knocked down either individually or in combination using siRNA in androgen independent prostate cancer PC-3 cells as confirmed by real-time PCR and western blotting. Cells were then treated with TRAIL, Etoposide, or Tunicamycin, and apoptosis assessed by PI DNA staining. Apoptosis was confirmed with Annexin V labelling and measurement of PARP cleavage, and was inhibited using the pan-caspase inhibitor, zVAD.fmk. Clonogenic assays and assessment of ID-1 expression by western blotting were used to measure recovery and proliferation. RESULTS: PC-3 are resistant to TRAIL induced apoptosis and have elevated expression of cIAP-1, cIAP-2 and XIAP. Combined knockdown sensitised PC-3 to TRAIL induced apoptosis, but not to Etoposide or Tunicmycin, with corresponding increases in caspase activity and PARP cleavage which was inhibited by ZVAD.fmk. Triple knock down decreased proliferation which was confirmed by decreased ID-1 expression. CONCLUSION: Simultaneous knock down of the IAPs not only sensitised the PC-3 to TRAIL but also inhibited their proliferation rates and clonogenic survival. The inability to alter sensitivity to other triggers of apoptosis suggests that this effect is specific for death receptor pathways and knock down might facilitate immune-surveillance mechanisms to counter cancer progression and, in combination with therapeutic approaches using TRAIL, could represent an important treatment strategy.

  7. Effects of cIAP-1, cIAP-2 and XIAP triple knockdown on prostate cancer cell susceptibility to apoptosis, cell survival and proliferation

    Directory of Open Access Journals (Sweden)

    Dowling Catherine

    2009-06-01

    Full Text Available Abstract Background Manipulating apoptotic resistance represents an important strategy for the treatment of hormone refractory prostate cancer. We hypothesised that the Inhibitor of Apoptosis (IAP Proteins may be mediating this resistance and knockdown of cIAP-1, cIAP-2 and XIAP would increase sensitivity to apoptosis. Methods cIAP-1, cIAP-2 and XIAP where knocked down either individually or in combination using siRNA in androgen independent prostate cancer PC-3 cells as confirmed by real-time PCR and western blotting. Cells were then treated with TRAIL, Etoposide, or Tunicamycin, and apoptosis assessed by PI DNA staining. Apoptosis was confirmed with Annexin V labelling and measurement of PARP cleavage, and was inhibited using the pan-caspase inhibitor, zVAD.fmk. Clonogenic assays and assessment of ID-1 expression by western blotting were used to measure recovery and proliferation. Results PC-3 are resistant to TRAIL induced apoptosis and have elevated expression of cIAP-1, cIAP-2 and XIAP. Combined knockdown sensitised PC-3 to TRAIL induced apoptosis, but not to Etoposide or Tunicmycin, with corresponding increases in caspase activity and PARP cleavage which was inhibited by ZVAD.fmk. Triple knock down decreased proliferation which was confirmed by decreased ID-1 expression. Conclusion Simultaneous knock down of the IAPs not only sensitised the PC-3 to TRAIL but also inhibited their proliferation rates and clonogenic survival. The inability to alter sensitivity to other triggers of apoptosis suggests that this effect is specific for death receptor pathways and knock down might facilitate immune-surveillance mechanisms to counter cancer progression and, in combination with therapeutic approaches using TRAIL, could represent an important treatment strategy.

  8. c-erbB2 and topoisomerase IIα protein expression independently predict poor survival in primary human breast cancer: a retrospective study

    International Nuclear Information System (INIS)

    Fritz, Peter; Cabrera, Cristina M; Dippon, Jürgen; Gerteis, Andreas; Simon, Wolfgang; Aulitzky, Walter E; Kuip, Heiko van der

    2005-01-01

    c-erbB2 (also known as HER-2/neu) and topoisomerase IIα are frequently overexpressed in breast cancer. The aim of the study was to analyze retrospectively whether the expression of c-erbB2 and topoisomerase IIα protein influences the long-term outcome of patients with primary breast cancer. In this study c-erbB2 and topoisomerase IIα protein were evaluated by immunohistochemistry in formalin-fixed paraffin-embedded tissue from 225 samples of primary breast cancer, obtained between 1986 and 1998. The prognostic value of these markers was analyzed. Of 225 primary breast tumor samples, 78 (34.7%) showed overexpression of either c-erbB2 (9.8%) or topoisomerase IIα protein (24.9%), whereas in 21 tumors (9.3%) both proteins were found to be overexpressed. Patients lacking both c-erbB2 and topoisomerase IIα overexpression had the best long-term survival. Overexpression of either c-erbB2 or topoisomerase IIα was associated with shortened survival, whereas patients overexpressing both c-erbB2 and topoisomerase IIα showed the worst disease outcome (P < 0.0001). Treatment with anthracyclines was not capable of reversing the negative prognostic impact of topoisomerase IIα or c-erbB2 overexpression. The results of this exploratory study suggest that protein expression of c-erbB2 and topoisomerase IIα in primary breast cancer tissues are independent prognostic factors and are not exclusively predictive factors for anthracycline response in patients with primary breast cancer

  9. Inhibition of c-Abl kinase activity renders cancer cells highly sensitive to mitoxantrone.

    Directory of Open Access Journals (Sweden)

    Kemal Alpay

    Full Text Available Although c-Abl has increasingly emerged as a key player in the DNA damage response, its role in this context is far from clear. We studied the effect of inhibition of c-Abl kinase activity by imatinib with chemotherapy drugs and found a striking difference in cell survival after combined mitoxantrone (MX and imatinib treatment compared to a panel of other chemotherapy drugs. The combinatory treatment induced apoptosis in HeLa cells and other cancer cell lines but not in primary fibroblasts. The difference in MX and doxorubicin was related to significant augmentation of DNA damage. Transcriptionally active p53 accumulated in cells in which human papillomavirus E6 normally degrades p53. The combination treatment resulted in caspase activation and apoptosis, but this effect did not depend on either p53 or p73 activity. Despite increased p53 activity, the cells arrested in G2 phase became defective in this checkpoint, allowing cell cycle progression. The effect after MX treatment depended partially on c-Abl: Short interfering RNA knockdown of c-Abl rendered HeLa cells less sensitive to MX. The effect of imatinib was decreased by c-Abl siRNA suggesting a role for catalytically inactive c-Abl in the death cascade. These findings indicate that MX has a unique cytotoxic effect when the kinase activity of c-Abl is inhibited. The treatment results in increased DNA damage and c-Abl-dependent apoptosis, which may offer new possibilities for potentiation of cancer chemotherapy.

  10. The preliminary study of setup errors' impact on dose distribution of image guide radiation therapy for head and neck cancer

    International Nuclear Information System (INIS)

    Xu Luying; Pan Jianji; Wang Xiaoliang; Bai Penggang; Li Qixin; Fei Zhaodong; Chen Chuanben; Ma Liqin; Tang Tianlan

    2011-01-01

    Objective: To measure the set-up errors of patients with head and neck (H and N) cancer during the image guided intensity-modulated radiotherapy (IMRT) treatment and analyze the impact of setup errors on dose distribution; then to further investigate the necessity of adjustment online for H and N cancer during IMRT treatment. Methods: Cone-beam CT (CBCT) scanning of thirty patients with H and N cancer were acquired by once weekly with a total of 6 times during IMRT treatment. The CBCT images and the original planning CT images were matched by the bony structure and worked out the translational errors of the x, y, z axis, as well as rotational errors. The dose distributions were recalculated based on the data of each setup error. The dose of planning target volume (PTV) and organs at risk were calculated in the re-planning, and than compared with the original plan by paired t-test. Results: The mean value of x, y, z axis translational set-up errors were (1.06 ± 0.95)mm, (0.95 ± 0.77)mm and (1.31 ± 1.07)mm, respectively. The rotational error of x, y, z axis were (1.04 ±0.791), (1.06 ±0.89) and (0.81 ±0.61 ), respectively. PTV 95% volume dose (D 95 ) and PTV minimal dose of re-planning for 6 times set-up were lower than original plan (6526.6 cGy : 6630.3 cGy, t =3.98, P =0.000 and 5632.6 cGy : 5792.5 cGy, t =- 2.89, P =0.007). Brain stem received 45 Gydose volume (V 45 ) and 1% brain stem volume dose (D 01 )were higher than original plan (3.54% : 2.75%, t =3.84, P =0.001 and 5129.7 cGy : 4919.3 cGy, t =4.36, P =0.000). Conclusions: The set-up errors led to the dose of PTV D 95 obviously insufficient and significantly increased V 45 , D 01 of the brainstem. So, adjustment online is necessary for H and N cancer during IMRT treatment. (authors)

  11. CYP2C19*2 and CYP2C19*17 variants and effect of tamoxifen on breast cancer recurrence

    DEFF Research Database (Denmark)

    Damkier, Per; Kjaersgaard, Anders; Barker, Kimberly A.

    2017-01-01

    *17 allele were 1.02 (CI 0.71-1.46) and 0.57 (CI 0.26-1.24), respectively. Accounting for CYP2D6 genotype status did not change these estimates. We found no evidence to support a clinically meaningful role of CYP2C19 polymorphisms and response to tamoxifen in breast cancer patients and, consequently, CYP2C19...... genotype status should not be included in clinical decisions on tamoxifen treatment....

  12. aThe dyslexia candidate gene DYX1C1 is a potential marker of poor survival in breast cancer

    Directory of Open Access Journals (Sweden)

    Rosin Gustaf

    2012-02-01

    Full Text Available Abstract Background The dyslexia candidate gene, DYX1C1, shown to regulate and interact with estrogen receptors and involved in the regulation of neuronal migration, has recently been proposed as a putative cancer biomarker. This study was undertaken to assess the prognostic value and therapy-predictive potential of DYX1C1 mRNA and protein expression in breast cancer. Methods DYX1C1 mRNA expression was assessed at the mRNA level in three independent population-derived patient cohorts. An association to estrogen/progesterone receptor status, Elston grade, gene expression subtype and lymph node status was analyzed within these cohorts. DYX1C1 protein expression was examined using immunohistochemistry in cancer and normal breast tissue. The statistical analyses were performed using the non-parametric Wilcoxon rank-sum test, ANOVA, Fisher's exact test and a multivariate proportional hazard (Cox model. Results DYX1C1 mRNA is significantly more highly expressed in tumors that have been classified as estrogen receptor α and progesterone receptor-positive. The expression of DYX1C1 among the molecular subtypes shows the lowest median expression within the basal type tumors, which are considered to have the worst prognosis. The expression of DYX1C1 is significantly lower in tumors graded as Elston grade 3 compared with grades 1 and 2. DYX1C1 protein is expressed in 88% of tumors and in all 10 normal breast tissues examined. Positive protein expression was significantly correlated to overall survival (Hazard ratio 3.44 [CI 1.84-6.42] of the patients but not to any of the variables linked with mRNA expression. Conclusion We show that the expression of DYX1C1 in breast cancer is associated with several clinicopathological parameters and that loss of DYX1C1 correlates with a more aggressive disease, in turn indicating that DYX1C1 is a potential prognostic biomarker in breast cancer.

  13. aThe dyslexia candidate gene DYX1C1 is a potential marker of poor survival in breast cancer

    International Nuclear Information System (INIS)

    Rosin, Gustaf; Hannelius, Ulf; Lindström, Linda; Hall, Per; Bergh, Jonas; Hartman, Johan; Kere, Juha

    2012-01-01

    The dyslexia candidate gene, DYX1C1, shown to regulate and interact with estrogen receptors and involved in the regulation of neuronal migration, has recently been proposed as a putative cancer biomarker. This study was undertaken to assess the prognostic value and therapy-predictive potential of DYX1C1 mRNA and protein expression in breast cancer. DYX1C1 mRNA expression was assessed at the mRNA level in three independent population-derived patient cohorts. An association to estrogen/progesterone receptor status, Elston grade, gene expression subtype and lymph node status was analyzed within these cohorts. DYX1C1 protein expression was examined using immunohistochemistry in cancer and normal breast tissue. The statistical analyses were performed using the non-parametric Wilcoxon rank-sum test, ANOVA, Fisher's exact test and a multivariate proportional hazard (Cox) model. DYX1C1 mRNA is significantly more highly expressed in tumors that have been classified as estrogen receptor α and progesterone receptor-positive. The expression of DYX1C1 among the molecular subtypes shows the lowest median expression within the basal type tumors, which are considered to have the worst prognosis. The expression of DYX1C1 is significantly lower in tumors graded as Elston grade 3 compared with grades 1 and 2. DYX1C1 protein is expressed in 88% of tumors and in all 10 normal breast tissues examined. Positive protein expression was significantly correlated to overall survival (Hazard ratio 3.44 [CI 1.84-6.42]) of the patients but not to any of the variables linked with mRNA expression. We show that the expression of DYX1C1 in breast cancer is associated with several clinicopathological parameters and that loss of DYX1C1 correlates with a more aggressive disease, in turn indicating that DYX1C1 is a potential prognostic biomarker in breast cancer

  14. Impact of Maspin Polymorphism rs2289520 G/C and Its Interaction with Gene to Gene, Alcohol Consumption Increase Susceptibility to Oral Cancer Occurrence.

    Science.gov (United States)

    Yang, Po-Yu; Miao, Nae-Fang; Lin, Chiao-Wen; Chou, Ying-Erh; Yang, Shun-Fa; Huang, Hui-Chuan; Chang, Hsiu-Ju; Tsai, Hsiu-Ting

    2016-01-01

    The purpose of this study was to identify gene polymorphisms of mammary serine protease inhibitor (Maspin) specific to patients with oral cancer susceptibility and clinicopathological status. Three single-nucleotide polymorphisms (SNPs) of the Maspin gene from 741 patients with oral cancer and 601 non-cancer controls were analyzed by real-time PCR. The participants with G/G homozygotes or with G/C heterozygotes of Maspin rs2289520 polymorphism had a 2.07-fold (p = 0.01) and a 2.01-fold (p = 0.02) risk of developing oral cancer compared to those with C/C homozygotes. Moreover, gene-gene interaction increased the risk of oral cancer susceptibility among subjects expose to oral cancer related risk factors, including areca, alcohol, and tobacco consumption. G allele of Maspin rs2289520 polymorphism may be a factor that increases the susceptibility to oral cancer. The interactions of gene to oral cancer-related environmental risk factors have a synergetic effect that can further enhance oral cancer development.

  15. Age-adjusted Charlson Comorbidity Index predicts prognosis of laryngopharyngeal cancer treated with radiation therapy.

    Science.gov (United States)

    Takemura, Kazuya; Takenaka, Yukinori; Ashida, Naoki; Shimizu, Kotaro; Oya, Ryohei; Kitamura, Takahiro; Yamamoto, Yoshifumi; Uno, Atsuhiko

    2017-12-01

    To examine the ability of comorbidity indices to predict the prognosis of laryngopharyngeal cancer and their association with treatment modalities. This retrospective study included 198 patients with laryngeal, hypopharyngeal, and oropharyngeal cancers. The effect of comorbidity indices on overall survival between surgery and (chemo)-radiation therapy ((C)RT) groups was analyzed. The cumulative incidence rates for cancer mortality and other mortalities according to the age-adjusted Charlson Comorbidity Index (ACCI) and Charlson Comorbidity Index (CCI) were compared. Univariate survival analyses showed a significant association between the ACCI and overall survival in the (C)RT group, but not in the surgery group. The association between the CCI and overall survival was not significant in either group. In multivariate analyses, a high ACCI score was an independent prognostic factor in the (C)RT group (HR 2.89, 95% confidence interval (CI) 1.28-6.49), but not in the surgery group (HR 1.39, 95%CI 0.27-5.43). The higher ACCI group had increased mortality from other causes compared with the lower ACCI group (5-year cumulative incidence, 8.5% and 17.8%, respectively, p = .003). The ACCI was a better prognostic factor than the CCI. Surgery may be more beneficial than radiation for patients with a high ACCI.

  16. The Role of c-FLIP(L) in Regulating Apoptotic Pathways in Prostate Cancer

    Science.gov (United States)

    2008-12-01

    and 0.1 to 0.5 ng of 32P-labeled double- stranded specific oligonucleotides (5,000–25,000 cpm ) in the presence of 2 Ag of poly(deoxyinosinic... advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact. c-Fos Represses c-FLIP(L) www.aacrjournals.org 9433 Cancer Res 2007; 67...of this article were defrayed in part by the payment of page charges.This article must therefore be hereby marked advertisement in accordance with18

  17. Tetrathiomolybdate sensitizes ovarian cancer cells to anticancer drugs doxorubicin, fenretinide, 5-fluorouracil and mitomycin C

    International Nuclear Information System (INIS)

    Kim, Kyu Kwang; Lange, Thilo S; Singh, Rakesh K; Brard, Laurent; Moore, Richard G

    2012-01-01

    Our recent study showed that tetrathiomolybdate (TM), a drug to treat copper overload disorders, can sensitize drug-resistant endometrial cancer cells to reactive oxygen species (ROS)-generating anticancer drug doxorubicin. To expand these findings in the present study we explore TM efficacy in combination with a spectrum of ROS-generating anticancer drugs including mitomycin C, fenretinide, 5-fluorouracil and doxorubicin in ovarian cancer cells as a model system. The effects of TM alone or in combination with doxorubicin, mitomycin C, fenretinide, or 5-fluorouracil were evaluated using a sulforhodamine B assay. Flow cytometry was used to detect the induction of apoptosis and ROS generation. Immunoblot analysis was carried out to investigate changes in signaling pathways. TM potentiated doxorubicin-induced cytotoxicity and modulated key regulators of apoptosis (PARP, caspases, JNK and p38 MAPK) in SKOV-3 and A2780 ovarian cancer cell lines. These effects were linked to the increased production of ROS, as shown in SKOV-3 cells. ROS scavenging by ascorbic acid blocked the sensitization of cells by TM. TM also sensitized SKOV-3 to mitomycin C, fenretinide, and 5-fluorouracil. The increased cytotoxicity of these drugs in combination with TM was correlated with the activity of ROS, loss of a pro-survival factor (e.g. XIAP) and the appearance of a pro-apoptotic marker (e.g. PARP cleavage). Our data show that TM increases the efficacy of various anticancer drugs in ovarian cancer cells in a ROS-dependent manner

  18. C Ramakrishnan

    Indian Academy of Sciences (India)

    Home; Journals; Resonance – Journal of Science Education. C Ramakrishnan. Articles written in Resonance – Journal of Science Education. Volume 6 Issue 10 October 2001 pp 48-56 General Article. Ramachandran and his Map · C Ramakrishnan · More Details Fulltext PDF. Volume 13 Issue 1 January 2008 pp 89-98 ...

  19. 7 CFR 301.89-5 - Movement of regulated articles from regulated areas.

    Science.gov (United States)

    2010-01-01

    ... 7 Agriculture 5 2010-01-01 2010-01-01 false Movement of regulated articles from regulated areas. 301.89-5 Section 301.89-5 Agriculture Regulations of the Department of Agriculture (Continued) ANIMAL... § 301.89-5 Movement of regulated articles from regulated areas. (a) Any regulated article may be moved...

  20. Radiochemical schemes of obtaining 89Sr and 90Y radionuclides

    International Nuclear Information System (INIS)

    Usarov, Z. O.

    2010-03-01

    Key words: strontium-89, yttrium-90, extraction and extraction-chromatographic purification of radionuclides, radiopharmaceuticals. Subjects of research: strontium-89 and yttrium-90 radionuclides and their chloride forms. Purpose of work is developing of radiochemical technologies on obtaining of 89 Sr and 90 Y on the WWR-SM reactor with high radionuclide purity. Methods of research: extraction and extraction-chromatographic methods of radionuclides separation, beta- and gamma-spectrometric methods of activity measuring. The results obtained and their novelty: Were determined the conformity to laws of Y and Sr distribution in two-phase systems TBP-HNO 3 , TBP-NH 4 NO 3 , TBP-HCI, HDEHP-NO 3 , HDEHP-NH 4 NO 3 and HDEHP-HCI. Were determined the conformity to laws of Y and Sr distribution in systems with craun ethers DB-18K-6 and DTBDB-18K-6 from water solutions of HNO 3 . Radiochemical technologies on obtaining of 89 Sr and 90 Y radionuclides including radiochemical process of yttrium target with using the systems TBP-HNO 3 and HDEHP/Teflone were developed. Practical value: the radiochemical technology of obtaining 89 Sr with high radionuclide purity was developed. The method of preparation a chloride compound of 89 SrCl 2 which is used as a drug form for preparation of 89 Sr- 'Metastron' was developed. The relatively simple method of on the way obtaining 90 Y in the reactor with high radionuclidic purity that is useful for follow using in medical practice was offered. Degree of embed and economic effectivity: the developed technologies have approbation in manufacturing conditions in Radiopreparat Enterprise of INP AS RU and were offered for receiving of domestic preparations against of import foreign analogues. The statement about using the invention by obtained patent is attached to dissertation. Field of application: the received results will be introduced in manufacture at Radiopreparat Enterprise of INP AS RU for receiving of domestic preparations

  1. Regulation of HGF and c-MET Interaction in Normal Ovary and Ovarian Cancer.

    Science.gov (United States)

    Kwon, Youngjoo; Godwin, Andrew K

    2017-04-01

    Binding of hepatocyte growth factor (HGF) to the c-MET receptor has mitogenic, motogenic, and morphogenic effects on cells. The versatile biological effects of HGF and c-MET interactions make them important contributors to the development of malignant tumors. We and others have demonstrated a therapeutic value in targeting the interaction of c-MET and HGF in epithelial ovarian cancer (EOC). However, both HGF and c-MET are expressed in the normal ovary as well. Therefore, it is important to understand the differences in mechanisms that control HGF signaling activation and its functional role in the normal ovary and EOC. In the normal ovary, HGF signaling may be under hormonal regulation. During ovulation, HGF-converting proteases are secreted and the subsequent activation of HGF signaling enhances the proliferation of ovarian surface epithelium in order to replenish the area damaged due to expulsion of the ovum. In contrast, EOC cells that exhibit epithelial characteristics constitutively express both c-MET and HGF-converting proteases such as urokinase-type plasminogen activator. In EOC, mechanisms to control the activation of HGF signaling are absent since HGF is provided locally from the tissue microenvironment as well as remotely throughout the body. Potential incessant HGF signaling in EOC may lead to an increase in proliferation, invasion through the stroma, and migration to other tissues of cancer cells. Therefore, targeting the interaction of c-MET and HGF would be beneficial in treating EOC.

  2. Alternative splicing enriched cDNA libraries identify breast cancer-associated transcripts

    Science.gov (United States)

    2010-01-01

    Background Alternative splicing (AS) is a central mechanism in the generation of genomic complexity and is a major contributor to transcriptome and proteome diversity. Alterations of the splicing process can lead to deregulation of crucial cellular processes and have been associated with a large spectrum of human diseases. Cancer-associated transcripts are potential molecular markers and may contribute to the development of more accurate diagnostic and prognostic methods and also serve as therapeutic targets. Alternative splicing-enriched cDNA libraries have been used to explore the variability generated by alternative splicing. In this study, by combining the use of trapping heteroduplexes and RNA amplification, we developed a powerful approach that enables transcriptome-wide exploration of the AS repertoire for identifying AS variants associated with breast tumor cells modulated by ERBB2 (HER-2/neu) oncogene expression. Results The human breast cell line (C5.2) and a pool of 5 ERBB2 over-expressing breast tumor samples were used independently for the construction of two AS-enriched libraries. In total, 2,048 partial cDNA sequences were obtained, revealing 214 alternative splicing sequence-enriched tags (ASSETs). A subset with 79 multiple exon ASSETs was compared to public databases and reported 138 different AS events. A high success rate of RT-PCR validation (94.5%) was obtained, and 2 novel AS events were identified. The influence of ERBB2-mediated expression on AS regulation was evaluated by capillary electrophoresis and probe-ligation approaches in two mammary cell lines (Hb4a and C5.2) expressing different levels of ERBB2. The relative expression balance between AS variants from 3 genes was differentially modulated by ERBB2 in this model system. Conclusions In this study, we presented a method for exploring AS from any RNA source in a transcriptome-wide format, which can be directly easily adapted to next generation sequencers. We identified AS transcripts

  3. The NOD2 3020insC Mutation in Women with Breast Cancer from the Bydgoszcz Region in Poland. First Results

    Directory of Open Access Journals (Sweden)

    Janiszewska Hanna

    2006-01-01

    Full Text Available Abstract The frameshift NOD2 gene mutation 3020insC is predominantly associated with Crohn's disease, but predisposes to many types of common cancers as well. We studied the frequency of this mutant NOD2 allele in 148 breast cancer women from the Bydgoszcz region in Poland. The NOD2 mutation was present in 8.8% of the patients. The mean age at breast cancer diagnosis of the mutation carriers was 43 years. We did not find any mutation in patients diagnosed with breast cancer after the age of 50 years. There was no association of the NOD2 mutation with a strong family history of breast cancer. On the contrary, the mutation frequency (11.4% was two times higher in women from families with a single case of breast cancer and with aggregation of other common types of cancer, especially digestive tract cancers. Low risk of breast cancer in the mutation carriers seems to be confirmed by finding the 3020insC mutation in three healthy parents of probands aged 73, 74 and 83 years, from three separate families.

  4. Impact of CYP2C8*3 on paclitaxel clearance in ovarian cancer patients

    DEFF Research Database (Denmark)

    Bergmann, Troels Korshøj; Vach, Werner; Gréen, Henrik

    be partly responsible for this variation. Paclitaxel is mainly metabolized by CYP2C8; SNPs have been investigated in this context before but conclusions are still lacking. We present a prospective study of paclitaxel clearance (CL) in 93 Caucasian females with epithelial ovarian cancer with regard...... to the CYP2C8 *1b, *1c, *3 and *4 genotypes. Material and methods All patients were diagnosed with primary ovarian/peritoneal cancer and received 175mg/m2 paclitaxel over 3 hrs plus carboplatin (AUC5-6) q3w. All patients gave written and verbal consent. The study was approved by ethics committees in Denmark...... and Sweden. Blood was sampled at 3hrs, 5-8 hrs and 18-24hrs after start of infusion. Total plasma paclitaxel was quantified using HPLC. CremophorEL® (CrEL) was determined as described by Sparreboom et al.1998. CL of unbound paclitaxel was estimated using total concentrations, CrEL and other parameters...

  5. Targeting of the MUC1-C Oncoprotein in Colitis-Associated Colorectal Cancer

    Science.gov (United States)

    2014-11-01

    separated by infiltrates of inflammatory cells and the presence of crypt abscess (lower left panel). With progression to dysplasia, the crypts are...Rajabi, H, et al., MUC1-C oncoprotein induces TCF7L2 activation and promotes cyclin D1 expression in human breast cancer cells. J Biol Chem, 2012

  6. Vascular endothelial growth factor (VEGF) gene polymorphisms and breast cancer risk in Punjabi population from North West India.

    Science.gov (United States)

    Kapahi, Ruhi; Guleria, Kamlesh; Sambyal, Vasudha; Manjari, Mridu; Sudan, Meena; Uppal, Manjit Singh; Singh, Neeti Rajan

    2014-11-01

    The purpose of this study was to evaluate the association of seven VEGF promoter polymorphisms with breast cancer risk in Punjabi population from North West India. We screened DNA samples of 102 sporadic breast cancer patients and 102 unrelated healthy, gender, and age-matched individuals for seven VEGF promoter polymorphisms [-417 C/T (rs833062), -172 C/A (rs59260042), -165 C/T (rs79469752), -160 C/T, -152 G/A (rs13207351), -141 A/C (rs28357093) and -116 G/A (rs1570360)] by direct sequencing. The frequency of GG, GA, and AA genotype of -152 G/A polymorphism was 26.47 vs 38.34%, 46.08 vs 51.96%, and 27.45 vs 9.80%, in patients and controls, respectively. VEGF -152 AA genotype was significantly associated with increased risk for breast cancer (OR = 4.04, 95%CI, 1.69-9.68, p = 0.001; recessive model OR = 3.48, 95%CI, 1.59-7.63, p = 0.001). For VEGF -116 G/A polymorphism, G and A allele frequencies were 65.2 vs 76.47% and 34.8 vs 23.53% in patients and controls, respectively. Individuals having -116 AA genotype (OR = 3.40; 95%CI, 1.24-9.37; p = 0.014) and A allele (OR = 1.73; 95%CI, 1.12-2.67; p = 0.012) were associated with increased risk for breast cancer. VEGF -165 C/T and -141 A/C polymorphisms were associated with reduced risk for breast cancer. There was significantly decreased frequency of CT genotype (4.90 vs 18.63%; p = 0.002) and T allele (2.45 vs 9.31%; p = 0.003) of -165 C/T polymorphism among breast cancer patients as compared to controls. VEGF -141 A and C allele frequency were 96.57 vs 91.18% and 3.43 vs 8.82% in patients and controls, respectively. Significant reduced risk for breast cancer was observed with AC genotype (OR = 0.34, 95%CI, 0.14-0.86; p = 0.019) and C allele (OR = 0.37; 95%CI, 0.15-0.89; p = 0.023) of -141 A/C polymorphism. We did not observe association of VEGF -417 T/C, -172 C/A, -160 C/T polymorphisms with breast cancer risk in the studied subjects (p > 0.05). The VEGF -152 G/A and -116 G/A polymorphisms were found to be significantly

  7. Olive phenolics as c-Met inhibitors: (--Oleocanthal attenuates cell proliferation, invasiveness, and tumor growth in breast cancer models.

    Directory of Open Access Journals (Sweden)

    Mohamed R Akl

    Full Text Available Dysregulation of the Hepatocyte growth factor (HGF/c-Met signaling axis upregulates diverse tumor cell functions, including cell proliferation, survival, scattering and motility, epithelial-to-mesenchymal transition (EMT, angiogenesis, invasion, and metastasis. (--Oleocanthal is a naturally occurring secoiridoid from extra-virgin olive oil, which showed antiproliferative and antimigratory activity against different cancer cell lines. The aim of this study was to characterize the intracellular mechanisms involved in mediating the anticancer effects of (--oleocanthal treatment and the potential involvement of c-Met receptor signaling components in breast cancer. Results showed that (--oleocanthal inhibits the growth of human breast cancer cell lines MDA-MB-231, MCF-7 and BT-474 while similar treatment doses were found to have no effect on normal human MCF10A cell growth. In addition, (--oleocanthal treatment caused a dose-dependent inhibition of HGF-induced cell migration, invasion and G1/S cell cycle progression in breast cancer cell lines. Moreover, (--oleocanthal treatment effects were found to be mediated via inhibition of HGF-induced c-Met activation and its downstream mitogenic signaling pathways. This growth inhibitory effect is associated with blockade of EMT and reduction in cellular motility. Further results from in vivo studies showed that (--oleocanthal treatment suppressed tumor cell growth in an orthotopic model of breast cancer in athymic nude mice. Collectively, the findings of this study suggest that (--oleocanthal is a promising dietary supplement lead with potential for therapeutic use to control malignancies with aberrant c-Met activity.

  8. Developing an Instrument to Measure Socioeconomic Disparities in Quality of Care for Men with Early Stage Prostate Cancer

    Science.gov (United States)

    2010-09-01

    April;2008:1988, released April 2008. 6. Yost K, Perkins C, Cohen R, et al. Socioeconomic status and breast cancer incidence in California for different...Fistula), 998.7 (Post-Op Foreign Substance Reaction), 604.0 (Orchitis with Abscess ), E870.0 (Acc Cut/Hem in Surgery), E870.4 (Acc Cut/Hem with Scope Exam...Surgical Complications: 595.89 (Cystitis Nec), 590.1 (Acute Pyelonephritis), 590.2 (Renal/Perirenal Abscess ), 590.8 (Pyelonephritis or pyonephrosis not

  9. [Relationship between the expression of beta-cat, cyclin D1 and c-myc and the occurance and biological behavior of pancreatic cancer].

    Science.gov (United States)

    Li, Yu-jun; Ji, Xiang-rui

    2003-06-01

    To study the relationship between the abnormal expression of beta-catenin (beta-cat) and the high expressions of cyclin D1 and c-myc and the occurance, proliferation, infiltration, metastasis and prognosis of pancreatic cancer, and to provide rational basis for the clinical diagnosis and treatment. Immunohistochemical PicTure trade mark was used to examine the expressions of beta-cat, cyclin D1 and c-myc in 47 cases of the cancerous tissue of pancreas, 12 cases of the pancreatic intraepithelial neoplasia and 10 cases of normal tissue of pancreas, respectively. Pancreatic cancer proliferation cell nuclear antigen (PCNA) was also tested as the index of the extent of proliferation of the pancreatic cancer. beta-cat was expressed normally in the 10 cases of the normal pancreatic tissue, while cyclin D1 and c-myc were negative. The expression rates of beta-cat, cyclin D1 and c-myc in the tissues of the pancreatic intraepithelial neoplasia and the pancreatic cancer had no significant difference [6/12 and 68.1% (32/47), 6/12 and 74.5% (35/47), 5/12 and 70.2% (33/47) respectively;P values were all more than 0.05]. The abnormal expression rate of beta-cat was significantly correlated to the metastasis of the pancreatic cancer and the one-year survival rate (both P 0.05). The expression rate of cyclin D1 was correlated with the proliferation of the pancreatic cancer and the extent of differentiation (both P 0.05). The expression rate of c-myc was not correlated with the size, the extent of proliferation, infiltration, metastasis, or one-year survival rate (both P > 0.05), but closely with the proliferation activity of the cancerous tissue of pancreas (P < 0.05). The abnormal expression of beta-cat and the high expressions of cyclin D1 and c-myc had a parallel relationship with the pancreatic intraepithelial neoplasia and pancreatic cancer (both P < 0.05, gamma = 1.000, 0.845, 0.437, 0.452). The abnormal expression of beta-cat activates cyclin D1 and c-myc, and results in the

  10. 28 CFR 0.89 - Authority to seize arms and munitions of war.

    Science.gov (United States)

    2010-07-01

    ... war. 0.89 Section 0.89 Judicial Administration DEPARTMENT OF JUSTICE ORGANIZATION OF THE DEPARTMENT OF JUSTICE Federal Bureau of Investigation § 0.89 Authority to seize arms and munitions of war. The Director... arms and munitions of war, and other articles, pursuant to section 1 of title VI of the act of June 15...

  11. Detection of high CD44 expression in oral cancers using the novel monoclonal antibody, C44Mab-5

    Directory of Open Access Journals (Sweden)

    Shinji Yamada

    2018-07-01

    Full Text Available CD44 is a transmembrane glycoprotein that regulates a variety of genes related to cell-adhesion, migration, proliferation, differentiation, and survival. A large number of alternative splicing isoforms of CD44, containing various combinations of alternative exons, have been reported. CD44 standard (CD44s, which lacks variant exons, is widely expressed on the surface of most tissues and all hematopoietic cells. In contrast, CD44 variant isoforms show tissue-specific expression patterns and have been extensively studied as both prognostic markers and therapeutic targets in cancer and other diseases. In this study, we immunized mice with CHO-K1 cell lines overexpressing CD44v3-10 to obtain novel anti-CD44 mAbs. One of the clones, C44Mab-5 (IgG1, kappa, recognized both CD44s and CD44v3-10. C44Mab-5 also reacted with oral cancer cells such as Ca9-22, HO-1-u-1, SAS, HSC-2, HSC-3, and HSC-4 using flow cytometry. Moreover, immunohistochemical analysis revealed that C44Mab-5 detected 166/182 (91.2% of oral cancers. These results suggest that the C44Mab-5 antibody may be useful for investigating the expression and function of CD44 in various cancers.

  12. Detection of high CD44 expression in oral cancers using the novel monoclonal antibody, C44Mab-5.

    Science.gov (United States)

    Yamada, Shinji; Itai, Shunsuke; Nakamura, Takuro; Yanaka, Miyuki; Kaneko, Mika K; Kato, Yukinari

    2018-07-01

    CD44 is a transmembrane glycoprotein that regulates a variety of genes related to cell-adhesion, migration, proliferation, differentiation, and survival. A large number of alternative splicing isoforms of CD44, containing various combinations of alternative exons, have been reported. CD44 standard (CD44s), which lacks variant exons, is widely expressed on the surface of most tissues and all hematopoietic cells. In contrast, CD44 variant isoforms show tissue-specific expression patterns and have been extensively studied as both prognostic markers and therapeutic targets in cancer and other diseases. In this study, we immunized mice with CHO-K1 cell lines overexpressing CD44v3-10 to obtain novel anti-CD44 mAbs. One of the clones, C 44 Mab-5 (IgG 1 , kappa), recognized both CD44s and CD44v3-10. C 44 Mab-5 also reacted with oral cancer cells such as Ca9-22, HO-1-u-1, SAS, HSC-2, HSC-3, and HSC-4 using flow cytometry. Moreover, immunohistochemical analysis revealed that C 44 Mab-5 detected 166/182 (91.2%) of oral cancers. These results suggest that the C 44 Mab-5 antibody may be useful for investigating the expression and function of CD44 in various cancers.

  13. Expression and clinical significance of extracellular matrix protein 1 and vascular endothelial growth factor-C in lymphatic metastasis of human breast cancer

    International Nuclear Information System (INIS)

    Wu, Qiu-Wan; She, Hong-Qiang; Liang, Jing; Huang, Yu-Fan; Yang, Qing-Mo; Yang, Qiao-Lu; Zhang, Zhi-Ming

    2012-01-01

    Extracellular matrix protein 1 (ECM1) and vascular endothelial growth factor-C (VEGF-C) are secretory glycoproteins that are associated with lymphangiogenesis; these proteins could, therefore, play important roles in the lymphatic dissemination of tumors. However, very little is known about their potential roles in lymphangiogenesis. The aim of this study was to investigate whether correlations exist between ECM1 and VEGF-C in human breast cancer, lymphangiogenesis, and the clinicopathological characteristics of the disease. ECM1 and VEGF-C mRNA and protein expression levels in 41 patients were investigated using real-time reverse transcriptase polymerase chain reaction (RT-PCR), or immunohistochemical (IHC) staining of breast cancer tissue, matched noncancerous breast epithelial tissues, and suspicious metastatic axillary lymph nodes. D2-40 labelled lymph vessels and lymphatic microvessel density (LMVD) were counted. Correlations between ECM1 or VEGF-C protein expression levels, LMVD, and clinicopathological parameters were statistically tested. The rate of ECM1 positive staining in breast cancer tissues was higher (31/41, 75.6%) than that in the corresponding epithelial tissues (4/41, 9.8%, P < 0.001) and lymph nodes (13/41, 31.7%, P < 0.001). Similarly, the VEGF-C expression rate in cancer specimens was higher (33/41, 80.5%) than in epithelial tissues (19/41, 46.3%, P < 0.01) or lymph nodes (15/41, 36.6%, P < 0.01). Higher ECM1 and VEGF-C mRNA expression levels were also detected in the tumor tissues, compared to the non-cancerous tissue types or lymph nodes (P < 0.05). ECM1 protein expression was positively correlated with the estrogen receptor status (P < 0.05) and LMVD (P < 0.05). LMVD in the ECM1- and VEGF-C-positive tumor specimens was higher than that in the tissue types with negative staining (P < 0.05). Both ECM1 and VEGF-C were overexpressed in breast cancer tissue samples. ECM1 expression was positively correlated with estrogen responsiveness and the

  14. cAMP-response-element-binding protein positively regulates breast cancer metastasis and subsequent bone destruction

    Energy Technology Data Exchange (ETDEWEB)

    Son, Jieun; Lee, Jong-Ho; Kim, Ha-Neui; Ha, Hyunil, E-mail: hyunil74@hotmail.com; Lee, Zang Hee, E-mail: zang1959@snu.ac.kr

    2010-07-23

    Research highlights: {yields} CREB is highly expressed in advanced breast cancer cells. {yields} Tumor-related factors such as TGF-{beta} further elevate CREB expression. {yields} CREB upregulation stimulates metastatic potential of breast cancer cells. {yields} CREB signaling is required for breast cancer-induced bone destruction. -- Abstract: cAMP-response-element-binding protein (CREB) signaling has been reported to be associated with cancer development and poor clinical outcome in various types of cancer. However, it remains to be elucidated whether CREB is involved in breast cancer development and osteotropism. Here, we found that metastatic MDA-MB-231 breast cancer cells exhibited higher CREB expression than did non-metastatic MCF-7 cells and that CREB expression was further increased by several soluble factors linked to cancer progression, such as IL-1, IGF-1, and TGF-{beta}. Using wild-type CREB and a dominant-negative form (K-CREB), we found that CREB signaling positively regulated the proliferation, migration, and invasion of MDA-MB-231 cells. In addition, K-CREB prevented MDA-MB-231 cell-induced osteolytic lesions in a mouse model of cancer metastasis. Furthermore, CREB signaling in cancer cells regulated the gene expression of PTHrP, MMPs, and OPG, which are closely involved in cancer metastasis and bone destruction. These results indicate that breast cancer cells acquire CREB overexpression during their development and that this CREB upregulation plays an important role in multiple steps of breast cancer bone metastasis.

  15. Protein Kinase C-ε Promotes EMT in Breast Cancer

    Science.gov (United States)

    Jain, Kirti; Basu, Alakananda

    2014-01-01

    Protein kinase C (PKC), a family of serine/threonine kinases, plays critical roles in signal transduction and cell regulation. PKCε, a member of the novel PKC family, is known to be a transforming oncogene and a tumor biomarker for aggressive breast cancers. In this study, we examined the involvement of PKCε in epithelial to mesenchymal transition (EMT), the process that leads the way to metastasis. Overexpression of PKCε was sufficient to induce a mesenchymal phenotype in non-tumorigenic mammary epithelial MCF-10 A cells. This was accompanied by a decrease in the epithelial markers, such as E-cadherin, zonula occludens (ZO)-1, and claudin-1, and an increase in mesenchymal marker vimentin. Transforming growth factor β (TGFβ) induced Snail expression and mesenchymal morphology in MCF-10 A cells, and these effects were partially reversed by the PKCε knockdown. PKCε also mediated cell migration and anoikis resistance, which are hallmarks of EMT. Thus, our study demonstrates that PKCε is an important mediator of EMT in breast cancer. PMID:24701121

  16. Influence of radiotherapy on expression of the proliferating cell nuclear antigen (PCNA) and c-fos in human cervical cancer

    International Nuclear Information System (INIS)

    Shi Mei; Wei Lichun; Sun Chaoyang; Ma Haixin; Guo Yan

    2001-01-01

    Objective: To investigate changes of proliferating cell nuclear antigen (PCNA) expression in human cervical cancer following irradiation. Methods: Immunohistochemical staining for PCNA was performed in frozen sections of formalin-fixed cervical cancer biopsy tissues. Results: The majority of the cancer cells showed PCNA-immunoreactivity before irradiation. Following irradiation (30-40 Gy/15-20 f) PCNA-immuno-positive staining was hardly detectable in most of the cancer cells. The PCNA-immunoreactivity, however, increased after radiotherapy, and moderate or heavy immuno-positive staining for PCNA was seen in irradiated mesenchymal tissue cells. On the other hand, after irradiation Fos-immunoreactivity decreased remarkably, and Fos-immuno-positive staining was hardly detectable in most of cancer cells. No obvious change in Fos-immuno-reactivity, however, was seen in mesenchymal connective tissue following irradiation. Conclusion: Irradiation inhibits PCNA and c-fos expression in cervical cancer cells whereas it induces the expression of PCNA in mesenchymal tissue cells. The present results suggest that expression of PCNA and c-fos may be regarded as a molecular marker for evaluating the cancer cell proliferation and mesenchymal tissue repair during radiotherapy of human cervical cancer

  17. Technique development of 3D dynamic CS-EPSI for hyperpolarized 13 C pyruvate MR molecular imaging of human prostate cancer.

    Science.gov (United States)

    Chen, Hsin-Yu; Larson, Peder E Z; Gordon, Jeremy W; Bok, Robert A; Ferrone, Marcus; van Criekinge, Mark; Carvajal, Lucas; Cao, Peng; Pauly, John M; Kerr, Adam B; Park, Ilwoo; Slater, James B; Nelson, Sarah J; Munster, Pamela N; Aggarwal, Rahul; Kurhanewicz, John; Vigneron, Daniel B

    2018-03-25

    The purpose of this study was to develop a new 3D dynamic carbon-13 compressed sensing echoplanar spectroscopic imaging (EPSI) MR sequence and test it in phantoms, animal models, and then in prostate cancer patients to image the metabolic conversion of hyperpolarized [1- 13 C]pyruvate to [1- 13 C]lactate with whole gland coverage at high spatial and temporal resolution. A 3D dynamic compressed sensing (CS)-EPSI sequence with spectral-spatial excitation was designed to meet the required spatial coverage, time and spatial resolution, and RF limitations of the 3T MR scanner for its clinical translation for prostate cancer patient imaging. After phantom testing, animal studies were performed in rats and transgenic mice with prostate cancers. For patient studies, a GE SPINlab polarizer (GE Healthcare, Waukesha, WI) was used to produce hyperpolarized sterile GMP [1- 13 C]pyruvate. 3D dynamic 13 C CS-EPSI data were acquired starting 5 s after injection throughout the gland with a spatial resolution of 0.5 cm 3 , 18 time frames, 2-s temporal resolution, and 36 s total acquisition time. Through preclinical testing, the 3D CS-EPSI sequence developed in this project was shown to provide the desired spectral, temporal, and spatial 5D HP 13 C MR data. In human studies, the 3D dynamic HP CS-EPSI approach provided first-ever simultaneously volumetric and dynamic images of the LDH-catalyzed conversion of [1- 13 C]pyruvate to [1- 13 C]lactate in a biopsy-proven prostate cancer patient with full gland coverage. The results demonstrate the feasibility to characterize prostate cancer metabolism in animals, and now patients using this new 3D dynamic HP MR technique to measure k PL , the kinetic rate constant of [1- 13 C]pyruvate to [1- 13 C]lactate conversion. © 2018 International Society for Magnetic Resonance in Medicine.

  18. Antidiarrheal Thymol Derivatives from Ageratina glabrata. Structure and Absolute Configuration of 10-Benzoyloxy-8,9-epoxy-6-hydroxythymol Isobutyrate

    Directory of Open Access Journals (Sweden)

    Celia Bustos-Brito

    2016-09-01

    Full Text Available Chemical investigation of the leaves from Ageratina glabrata yielded four new thymol derivatives, namely: 10-benzoyloxy-8,9-dehydro-6-hydroxythymol isobutyrate (4, 10-benzoyloxy-8,9-dehydrothymol (5, 10-benzoyloxythymol (6 and 10-benzoyloxy-6,8-dihydroxy-9-isobutyryl-oxythymol (7. In addition, (8S-10-benzoyloxy-8,9-epoxy-6-hydroxythymol isobutyrate (1, together with other two already known thymol derivatives identified as 10-benzoyloxy-8,9-epoxy-6-methoxythymol isobutyrate (2 and 10-benzoyloxy-8,9-epoxythymol isobutyrate (3 were also obtained. In this paper, we report the structures and complete assignments of the 1H and 13C-NMR data of compounds 1–7, and the absolute configuration for compound 1, unambiguously established by single crystal X-ray diffraction, and evaluation of the Flack parameter. The in vitro antiprotozoal assay showed that compound 1 and its derivative 1a were the most potent antiamoebic and antigiardial compounds. Both compounds showed selectivity and good antiamoebic activity comparable to emetine and metronidazole, respectively, two antiprotozoal drugs used as positive controls. In relation to anti-propulsive effect, compound 1 and 1a showed inhibitory activity, with activities comparable to quercetin and compound 9, two natural antipropulsive compounds used as positive controls. These data suggest that compound 1 may play an important role in antidiarrheal properties of Ageratina glabrata.

  19. Opposing effects of low versus high concentrations of water soluble vitamins/dietary ingredients Vitamin C and niacin on colon cancer stem cells (CSCs).

    Science.gov (United States)

    Sen, Utsav; Shenoy P, Sudheer; Bose, Bipasha

    2017-10-01

    Colorectal cancer is one of the global causes of cancer deaths. Cancer stem cells (CSCs) inside the tumour niche responsible for metastasis and relapses, and hence need to be targeted for cancer therapeutics. Although dietary fibre and lifestyle changes have been recommended as measures for colorectal cancer prevention, no such recommendations are available for using water soluble vitamins as prophylaxis measure for colorectal cancers. High dose of Vitamin C has been proven to selectively kill colon cancer cells having BRAF and KRAS mutations by inducing oxidative stress. In this study, we show for the first time the opposing effects of the low and high dose of Vitamin C and vitamin B3 on colon CSCs isolated from HT-29 and HCT-15 colorectal carcinoma cell lines. At small doses, both of these vitamins exerted a cell proliferative effect only on CSCs, while there was no change in the proliferation status of non-stem cancer cells and wild-type (WT) populations. On the other hand, the death effects induced by high doses of Vitamin C and B3 were of the order of 50-60% and ∼30% on CSCs from HT-29 and HCT15, respectively. Interestingly, the control fibroblast cell line (NIH3T3) was highly refractory all the tested concentrations of Vitamin C and B3, except for the highest dose - 10,000 μg of Vitamin C that induced only 15% of cell death. Hence, these results indicate the future scope of use of therapeutic doses of Vitamin C and B3 especially in patients with advanced colorectal cancer. © 2017 International Federation for Cell Biology.

  20. Radiotherapy Suppresses Bone Cancer Pain through Inhibiting Activation of cAMP Signaling in Rat Dorsal Root Ganglion and Spinal Cord

    Directory of Open Access Journals (Sweden)

    Guiqin Zhu

    2016-01-01

    Full Text Available Radiotherapy is one of the major clinical approaches for treatment of bone cancer pain. Activation of cAMP-PKA signaling pathway plays important roles in bone cancer pain. Here, we examined the effects of radiotherapy on bone cancer pain and accompanying abnormal activation of cAMP-PKA signaling. Female Sprague-Dawley rats were used and received tumor cell implantation (TCI in rat tibia (TCI cancer pain model. Some of the rats that previously received TCI treatment were treated with X-ray radiation (radiotherapy. Thermal hyperalgesia and mechanical allodynia were measured and used for evaluating level of pain caused by TCI treatment. PKA mRNA expression in dorsal root ganglion (DRG was detected by RT-PCR. Concentrations of cAMP, IL-1β, and TNF-α as well as PKA activity in DRG and the spinal cord were measured by ELISA. The results showed that radiotherapy significantly suppressed TCI-induced thermal hyperalgesia and mechanical allodynia. The level of PKA mRNA in DRG, cAMP concentration and PKA activity in DRG and in the spinal cord, and concentrations of IL-1β and TNF-α in the spinal cord were significantly reduced by radiotherapy. In addition, radiotherapy also reduced TCI-induced bone loss. These findings suggest that radiotherapy may suppress bone cancer pain through inhibition of activation of cAMP-PKA signaling pathway in DRG and the spinal cord.

  1. 40 CFR 89.301 - Scope; applicability.

    Science.gov (United States)

    2010-07-01

    ... subpart B of part 89. (b) Exhaust gases, either raw or dilute, are sampled while the test engine is operated using an 8-mode test cycle on an engine dynamometer. The exhaust gases receive specific component analysis determining concentration of pollutant, exhaust volume, the fuel flow, and the power output during...

  2. 42 CFR 413.89 - Bad debts, charity, and courtesy allowances.

    Science.gov (United States)

    2010-10-01

    ... 42 Public Health 2 2010-10-01 2010-10-01 false Bad debts, charity, and courtesy allowances. 413.89... Categories of Costs § 413.89 Bad debts, charity, and courtesy allowances. Link to an amendment published at 75 FR 49198, Aug. 12, 2010. (a) Principle. Bad debts, charity, and courtesy allowances are deductions...

  3. K C Bhamu

    Indian Academy of Sciences (India)

    Home; Journals; Pramana – Journal of Physics. K C BHAMU. Articles written in Pramana – Journal of Physics. Volume 89 Issue 1 July 2017 pp 11 Research Article. Density functional study of A g S c O 2 : Electronic and optical properties · K C BHAMU JAGRATI SAHARIYA RISHI VYAS K R PRIOLKAR · More Details ...

  4. The prevalence of deranged C-reactive protein and albumin in patients with incurable cancer approaching death.

    Directory of Open Access Journals (Sweden)

    Sarah Gray

    Full Text Available Amongst patients with incurable cancer approaching death, cachexia is common and associated with adverse outcomes. The term cachexia lacks a universally accepted definition and there is no consensus regarding which variables are to be measured. Furthermore, an elevated C-reactive protein is a common clinical challenge in this patient group. This study aims to add to the ongoing discussion regarding the definition of cancer cachexia and to study the role of C-reactive protein and s-albumin in this context.A 1-year cohort, consisting of 155 cancer patients enrolled in a specialized palliative home care team in the city of Östersund, Sweden, that were deceased during the year of 2015 was studied. Laboratory measures were studied within 0-30 and 31-60 days prior to death. C-reactive protein >10 mg/L and coinciding s-albumin <30 g/L was referred to as "laboratory cachexia". Also, the number of days from the first found "laboratory cachexia" until death was noted.The prevalence of "laboratory cachexia" was 85% 0-30 days prior to death compared to 66% 31-60 days prior to death (p<0.01. The majority of patients (75% had an onset of "laboratory cachexia" within 0-120 days prior to death, with a median of 47 days. The median values for C-reactive protein and s-albumin within 0-30 days prior to death were 84mg/L and 23g/L respectively.Could markedly deranged values of C-reactive protein and s-albumin, such as found in this study, signal a relatively short remaining survival time in patients with incurable cancer and no clinical signs of ongoing infection? The role of "laboratory cachexia" in this context as well as the cut off values for the laboratory measures included may be further discussed.

  5. Corelation between the crystallisation process and change in thermoelectromotive force for the amorphous alloy Fe89.8Ni1.5Si5.2B3C0.5

    Directory of Open Access Journals (Sweden)

    Maričić Aleksa M.

    2003-01-01

    Full Text Available Thermal and kinetic analyses of the structural changes for the amorphous alloy Fe89.8Ni1.5Si5.2B3C0.5, during the processes of non-isothermal heating and isothermal annealing, have been performed. The crystallisation process has been investigated using the method of differential scanning calorimetry (DSC. It is determined that this alloy crystalizes through three different stages. Changes in the electronic structure of the amorphous tape, for the temperature range 20 to 700ºC have been studied. This was achieved by measuring the thermoelectromotive force (TEMS, of the thermo pair made of two tapes with same chemical structure of the alloy FeNiSiBC, but different atomic structure: one is in the crystal state (CL and the other is in the amorphous state (AM. Analysis of the temperature dependence of the electromotive force has shown the following: the investigated alloy is thermically stable up to 450ºC and changes in the atomic structure as well as equalising of the free electron density in both parts of the thermo pair AM-CL, take place in the temperature range from 450 to 550ºC. Kinetic parameters of the process were determined by measuring time dependence of the TEMS in isothermic conditions at the temperatures 450, 480 and 510ºC.

  6. [Protein kinase A inhibitor H-89 blocks polyploidization of SP600125-induced CMK cells by regulating phosphorylation of ribosomal protein S6 kinase 1].

    Science.gov (United States)

    Zhao, Song; Yang, Jingang; Li, Changling; Xing, Sining; Yu, Ying; Liu, Shuo; Pu, Feifei; Ma, Dongchu

    2016-10-01

    Objective To investigate the regulatory effect of post-translation modification of ribosomal protein S6 kinase 1 (S6K1) on the polyploidization of megakaryocytes. Methods SP600125, a c-Jun N-terminal kinase (JNK) inhibitor, and H-89, a cAMP-dependent protein kinase (PKA) inhibitor, were used to treat CMK cells separately or in combination. With propidium iodide (PI) to dye DNA in the treated cells, the relative DNA content was detected by flow cytometry, and then the DNA polyploidy was analyzed. The change of expression and phosphorylation of ribosomal protein S6 kinase 1 (S6K1), an important mammalian target of rapamycin (mTOR) downstream target molecule, was analyzed by Western blotting. Molecular docking study and kinase activity assay were performed to analyze the combination of H-89 with S6K1 and the effect of H-89 on the activity of S6K1 kinase. Results SP600125 induced CMK cell polyploidization in a time-dependent and dose-dependent manner. At the same time, it increased the phosphorylation of S6K1 at Thr421/Ser424 and decreased the phosphorylation of S6K1 at Thr389. H-89 not only blocked polyploidization, but also decreased the phosphorylation of S6K1 at Thr421/Ser424 and increased the phosphorylation of S6K1 at Thr389. Molecular docking and kinase activity assay showed that H-89 occupied the ATP binding sites of S6K1 and inhibited its activity. Noticeably, both H-89 and SP600125 inhibited the activity of PKA. Moreover, the two drugs further inhibited the activity of PKA when used together. Therefore, these data indicated that H-89 blocked the SP600125-induced polyploidization of CMK cells mainly by changing S6K1 phosphorylation state, rather than its inhibitory effect on PKA. Conclusion H-89 can block the polyploidization of SP600125-induced CMK cells by regulating S6K1 phosphorylation state.

  7. Association of Matrix Metalloproteinase-7 Genotypes to the Risk of Oral Cancer in Taiwan.

    Science.gov (United States)

    Shih, Liang-Chun; Li, Ching-Hao; Sun, Kuo-Ting; Chen, Liang-Yu; Hsu, Che-Lun; Hung, Yi-Wen; Wu, Cheng-Nan; Hsia, Te-Chun; Shen, Te-Chun; Chang, Wen-Shin; Shih, Tzu-Ching; Tsai, Chia-Wen; Bau, DA-Tian

    2018-04-01

    Matrix metalloproteinases (MMPs) play a critical role in inflammation and carcinogenesis, and the expression of mRNA MMP7 in oral squamous cell carcinoma tissues was higher than in the oral lichen planus or normal oral mucosa. However, the genotypic role of MMP7 has never been examined in oral cancer. Therefore, in the current study we aimed to examine the contribution of genotypic variants in the promoter region of MMP7 (A-181G and C-153T) to oral cancer risk in Taiwan. In this hospital-based case-control study, 788 patients with oral cancer and 956 gender-and age-matched healthy controls were genotyped for MMP7 A-181G and C-153T via polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) methodology. The distribution pattern of AA, AG and GG for MMP7 promoter A-181G genotype was 88.2, 10.4 and 1.4% in the oral cancer patient group and 89.0, 9.3 and 1.7% in the healthy control group, respectively (p for trend=0.6779), non-significantly differentially distributed between the two groups. There is no polymorphic genotype for MMP7 C-153T among Taiwanese. The comparisons in allelic frequency distribution also support the findings that G allele may not be the risk determinant allele for oral cancer. There is no interaction between the genotypes of MMP7 with age, gender, smoking, alcohol or betel quid consumption on oral cancer risk. Our results indicate that the MMP7 promoter genotypes only play an indirect role in determining the personal susceptibility to oral cancer in Taiwan. Copyright© 2018, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

  8. Lactobacillus paracasei GMNL-32, Lactobacillus reuteri GMNL-89 and L. reuteri GMNL-263 ameliorate hepatic injuries in lupus-prone mice.

    Science.gov (United States)

    Hsu, Tsai-Ching; Huang, Chih-Yang; Liu, Chung-Hsien; Hsu, Kuo-Ching; Chen, Yi-Hsing; Tzang, Bor-Show

    2017-04-01

    Probiotics are known to regulate host immunity by interacting with systemic and mucosal immune cells as well as intestinal epithelial cells. Supplementation with certain probiotics has been reported to be effective against various disorders, including immune-related diseases. However, little is known about the effectiveness of Lactobacillus paracasei GMNL-32 (GMNL-32), Lactobacillus reuteri GMNL-89 (GMNL-89) and L. reuteri GMNL-263 (GMNL-263) in the management of autoimmune diseases, especially systemic lupus erythematosus (SLE). NZB/W F1 mice, which are a lupus-prone animal model, were orally gavaged with GMNL-32, GMNL-89 or GMNL-263 to investigate the effects of these Lactobacillus strains on liver injuries in NZB/W F1 mice. The results thus obtained reveal that supplementary GMNL-32, GMNL-89 or GMNL-263 in NZB/W F1 mice ameliorates hepatic apoptosis and inflammatory indicators, such as matrix metalloproteinase-9 activity and C-reactive protein and inducible nitric oxide synthase expressions. In addition, supplementation with GMNL-32, GMNL-89 or GMNL-263 in NZB/W F1 mice reduced the expressions of hepatic IL-1β, IL-6 and TNF-α proteins by suppressing the mitogen-activated protein kinase and NF-κB signalling pathways. These findings, presented here for the first time, reveal that GMNL-32, GMNL-89 and GMNL-263 mitigate hepatic inflammation and apoptosis in lupus-prone mice and may support an alternative remedy for liver disorders in cases of SLE.

  9. Molecular, cellular and physiological characterization of the cancer cachexia-inducing C26 colon carcinoma in mouse

    Energy Technology Data Exchange (ETDEWEB)

    Aulino, Paola [Department of Histology and Medical Embryology, Sapienza University of Rome, Via Scarpa 16, 00161 Rome, Italy and Interuniversity Institute of Myology (Italy); Faiola, Fabio [DVM Veterinarian chief, Health Status and Animal Welfare, Sapienza University of Rome, Via Scarpa 16, 00161 Rome (Italy); Adamo, Sergio; Coletti, Dario; Berardi, Emanuele; Cardillo, Veronica M; Rizzuto, Emanuele; Perniconi, Barbara; Ramina, Carla; Padula, Fabrizio [Department of Histology and Medical Embryology, Sapienza University of Rome, Via Scarpa 16, 00161 Rome, Italy and Interuniversity Institute of Myology (Italy); Spugnini, Enrico P [SAFU Department, Regina Elena Cancer Institute, Via delle Messi d' Oro 156, 00158 Rome (Italy); Baldi, Alfonso [Department Biochemistry, Section of Pathology, Second University of Naples, Via L. Armanni 5, 80138 Naples (Italy)

    2010-07-08

    The majority of cancer patients experience dramatic weight loss, due to cachexia and consisting of skeletal muscle and fat tissue wasting. Cachexia is a negative prognostic factor, interferes with therapy and worsens the patients' quality of life by affecting muscle function. Mice bearing ectopically-implanted C26 colon carcinoma are widely used as an experimental model of cancer cachexia. As part of the search for novel clinical and basic research applications for this experimental model, we characterized novel cellular and molecular features of C26-bearing mice. A fragment of C26 tumor was subcutaneously grafted in isogenic BALB/c mice. The mass growth and proliferation rate of the tumor were analyzed. Histological and cytofluorometric analyses were used to assess cell death, ploidy and differentiation of the tumor cells. The main features of skeletal muscle atrophy, which were highlighted by immunohistochemical and electron microscopy analyses, correlated with biochemical alterations. Muscle force and resistance to fatigue were measured and analyzed as major functional deficits of the cachectic musculature. We found that the C26 tumor, ectopically implanted in mice, is an undifferentiated carcinoma, which should be referred to as such and not as adenocarcinoma, a common misconception. The C26 tumor displays aneuploidy and histological features typical of transformed cells, incorporates BrdU and induces severe weight loss in the host, which is largely caused by muscle wasting. The latter appears to be due to proteasome-mediated protein degradation, which disrupts the sarcomeric structure and muscle fiber-extracellular matrix interactions. A pivotal functional deficit of cachectic muscle consists in increased fatigability, while the reported loss of tetanic force is not statistically significant following normalization for decreased muscle fiber size. We conclude, on the basis of the definition of cachexia, that ectopically-implanted C26 carcinoma represents a

  10. Molecular, cellular and physiological characterization of the cancer cachexia-inducing C26 colon carcinoma in mouse

    International Nuclear Information System (INIS)

    Aulino, Paola; Faiola, Fabio; Adamo, Sergio; Coletti, Dario; Berardi, Emanuele; Cardillo, Veronica M; Rizzuto, Emanuele; Perniconi, Barbara; Ramina, Carla; Padula, Fabrizio; Spugnini, Enrico P; Baldi, Alfonso

    2010-01-01

    The majority of cancer patients experience dramatic weight loss, due to cachexia and consisting of skeletal muscle and fat tissue wasting. Cachexia is a negative prognostic factor, interferes with therapy and worsens the patients' quality of life by affecting muscle function. Mice bearing ectopically-implanted C26 colon carcinoma are widely used as an experimental model of cancer cachexia. As part of the search for novel clinical and basic research applications for this experimental model, we characterized novel cellular and molecular features of C26-bearing mice. A fragment of C26 tumor was subcutaneously grafted in isogenic BALB/c mice. The mass growth and proliferation rate of the tumor were analyzed. Histological and cytofluorometric analyses were used to assess cell death, ploidy and differentiation of the tumor cells. The main features of skeletal muscle atrophy, which were highlighted by immunohistochemical and electron microscopy analyses, correlated with biochemical alterations. Muscle force and resistance to fatigue were measured and analyzed as major functional deficits of the cachectic musculature. We found that the C26 tumor, ectopically implanted in mice, is an undifferentiated carcinoma, which should be referred to as such and not as adenocarcinoma, a common misconception. The C26 tumor displays aneuploidy and histological features typical of transformed cells, incorporates BrdU and induces severe weight loss in the host, which is largely caused by muscle wasting. The latter appears to be due to proteasome-mediated protein degradation, which disrupts the sarcomeric structure and muscle fiber-extracellular matrix interactions. A pivotal functional deficit of cachectic muscle consists in increased fatigability, while the reported loss of tetanic force is not statistically significant following normalization for decreased muscle fiber size. We conclude, on the basis of the definition of cachexia, that ectopically-implanted C26 carcinoma represents

  11. Molecular, cellular and physiological characterization of the cancer cachexia-inducing C26 colon carcinoma in mouse

    Directory of Open Access Journals (Sweden)

    Baldi Alfonso

    2010-07-01

    Full Text Available Abstract Background The majority of cancer patients experience dramatic weight loss, due to cachexia and consisting of skeletal muscle and fat tissue wasting. Cachexia is a negative prognostic factor, interferes with therapy and worsens the patients' quality of life by affecting muscle function. Mice bearing ectopically-implanted C26 colon carcinoma are widely used as an experimental model of cancer cachexia. As part of the search for novel clinical and basic research applications for this experimental model, we characterized novel cellular and molecular features of C26-bearing mice. Methods A fragment of C26 tumor was subcutaneously grafted in isogenic BALB/c mice. The mass growth and proliferation rate of the tumor were analyzed. Histological and cytofluorometric analyses were used to assess cell death, ploidy and differentiation of the tumor cells. The main features of skeletal muscle atrophy, which were highlighted by immunohistochemical and electron microscopy analyses, correlated with biochemical alterations. Muscle force and resistance to fatigue were measured and analyzed as major functional deficits of the cachectic musculature. Results We found that the C26 tumor, ectopically implanted in mice, is an undifferentiated carcinoma, which should be referred to as such and not as adenocarcinoma, a common misconception. The C26 tumor displays aneuploidy and histological features typical of transformed cells, incorporates BrdU and induces severe weight loss in the host, which is largely caused by muscle wasting. The latter appears to be due to proteasome-mediated protein degradation, which disrupts the sarcomeric structure and muscle fiber-extracellular matrix interactions. A pivotal functional deficit of cachectic muscle consists in increased fatigability, while the reported loss of tetanic force is not statistically significant following normalization for decreased muscle fiber size. Conclusions We conclude, on the basis of the definition of

  12. Prostate cancer: a comparative study of {sup 11}C-choline PET and MR imaging combined with proton MR spectroscopy

    Energy Technology Data Exchange (ETDEWEB)

    Yamaguchi, Takako; Lee, Jin; Takahashi, Nobukazu; Oka, Takashi; Shizukuishi, Kazuya; Inoue, Tomio [Yokohama City University School of Medicine, Department of Radiology, Yokohama (Japan); Uemura, Hiroji; Kubota, Yoshinobu [Yokohama City University School of Medicine, Department of Urology, Kanagawa (Japan); Sasaki, Takeshi [Yokohama City University School of Medicine, Department of Pathology, Kanagawa (Japan); Endou, Hisashi [Yokohama City University School of Medicine, Department of Pharmacy, Kanagawa (Japan)

    2005-07-01

    Prostate cancer is difficult to visualise in its early stages using current imaging technology. The present study aimed to clarify the utility of {sup 11}C-choline PET for localising and evaluating cancer lesions in patients with prostate cancer by conducting a prospective comparison with magnetic resonance (MR) imaging combined with proton MR spectroscopy. PET and MR imaging combined with proton MR spectroscopy were performed in 20 patients with prostate cancer. Correlations among the metabolite ratio of choline + creatine to citrate (Cho+Cr/Ci) on MR spectroscopy, serum PSA and maximum standardised uptake value (SUV{sub max}) of {sup 11}C-choline were assessed. The location of the primary lesion was assessed by the site of SUV{sub max} and the laterality of the highest Cho+Cr/Ci ratio and confirmed by examination of surgical pathology specimens (n=16). PET exhibited a diagnostic sensitivity of 100% (20/20) for primary lesions, while the sensitivities of MR imaging and MR spectroscopy were 60% (12/20) and 65% (13/20), respectively. Weak linear correlations were observed between SUV{sub max} and serum PSA (r=0.52, p<0.05), and between SUV{sub max} and Cho+Cr/Ci ratio (r=0.49, p<0.05). Regarding the localisation of main primary lesions, PET results agreed with pathological findings in 13 patients (81%) ({kappa}=0.59), while MR spectroscopy results were in accordance with pathological findings in eight patients (50%) ({kappa}=0.11). This preliminary study suggests that {sup 11}C-choline PET may provide more accurate information regarding the localisation of main primary prostate cancer lesions than MR imaging/MR spectroscopy. A further clinical study of {sup 11}C-choline PET in a large number of patients suspected of prostate cancer will be necessary to determine the clinical utility of {sup 11}C-choline PET in patients who clinically require biopsy. (orig.)

  13. 30 CFR 7.89 - Test to determine the particulate index.

    Science.gov (United States)

    2010-07-01

    ... 30 Mineral Resources 1 2010-07-01 2010-07-01 false Test to determine the particulate index. 7.89... Use in Underground Coal Mines § 7.89 Test to determine the particulate index. The test shall be... measured and recorded at each test mode. (ii) The data required for use in the particulate index...

  14. Propolin C Inhibited Migration and Invasion via Suppression of EGFR-Mediated Epithelial-to-Mesenchymal Transition in Human Lung Cancer Cells

    Directory of Open Access Journals (Sweden)

    Jih-Tung Pai

    2018-01-01

    Full Text Available Controlling lung cancer cell migration and invasion via epithelial-to-mesenchymal transition (EMT through the regulation of epidermal growth factor receptor (EGFR signaling pathway has been demonstrated. Searching biological active phytochemicals to repress EGFR-regulated EMT might prevent lung cancer progression. Propolis has been used as folk medicine in many countries and possesses anti-inflammatory, antioxidant, and anticancer activities. In this study, the antimigration and anti-invasion activities of propolin C, a c-prenylflavanone from Taiwanese propolis, were investigated on EGFR-regulated EMT signaling pathway. Cell migration and invasion activities were dose-dependently suppressed by noncytotoxic concentration of propolin C. Downregulations of vimentin and snail as well as upregulation of E-cadherin expressions were through the inhibition of EGFR-mediated phosphatidylinositol-3-kinase/protein kinase B (PI3K/Akt and extracellular signal-regulated kinase (ERK signaling pathway in propolin C-treated cells. In addition, EGF-induced migration and invasion were suppressed by propolin C-treated A549 lung cancer cells. No significant differences in E-cadherin expression were observed in EGF-stimulated cells. Interestingly, EGF-induced expressions of vimentin, snail, and slug were suppressed through the inhibition of PI3K/Akt and ERK signaling pathway in propolin C-treated cells. Inhibition of cell migration and invasion by propolin C was through the inhibition of EGF/EGFR-mediated signaling pathway, followed by EMT suppression in lung cancer.

  15. Radiation-induced VEGF-C expression and endothelial cell proliferation in lung cancer

    Energy Technology Data Exchange (ETDEWEB)

    Chen, Yu-Hsuan [National Taiwan University Hospital, Department of Oncology, Taipei (China); National Taiwan University, Pharmacological Institute, College of Medicine, Taipei (China); Pan, Shiow-Lin; Wang, Jing-Chi; Teng, Che-Ming [National Taiwan University, Pharmacological Institute, College of Medicine, Taipei (China); Kuo, Sung-Hsin [National Taiwan University Hospital, Department of Oncology, Taipei (China); National Taiwan University College of Medicine, Department of Internal Medicine, Taipei (China); Cheng, Jason Chia-Hsien [National Taiwan University Hospital, Department of Oncology, Taipei (China); National Taiwan University College of Medicine, Graduate Institute of Clinical Medicine, Taipei (China)

    2014-12-15

    The present study was undertaken to investigate whether radiation induces the expression of vascular endothelial growth factor C (VEGF-C) through activation of the PI3K/Akt/mTOR pathway,subsequently affecting endothelial cells. Radiotherapy-induced tumor micro-lymphatic vessel density (MLVD) was determined in a lung cancer xenograft model established in SCID mice. The protein expression and phosphorylation of members of the PI3K/Akt/mTOR pathway and VEGF-C secretion and mRNA expression in irradiated lung cancer cells were assessed by Western blot analysis, enzyme-linked immunosorbent assays (ELISAs), and reverse transcriptase-polymerase chain reaction (RT-PCR). Moreover, specific chemical inhibitors were used to evaluate the role of the PI3K/Akt/mTOR signaling pathway. Conditioned medium (CM) from irradiated control-siRNA or VEGF-C-siRNA-expressing A549 cells was used to evaluate the proliferation of endothelial cells by the MTT assay. Radiation increased VEGF-C expression in a dose-dependent manner over time at the protein but not at the mRNA level. Radiation also up-regulated the phosphorylation of Akt, mTOR, 4EBP, and eIF4E, but not of p70S6K. Radiation-induced VEGF-C expression was down-regulated by LY294002 and rapamycin (both p < 0.05). Furthermore, CM from irradiated A549 cells enhanced human umbilical vein endothelial cell (HUVEC) and lymphatic endothelial cell (LEC) proliferation, which was not observed with CM from irradiated VEGF-C-siRNA-expressing A549 cells. Radiation-induced activation of the PI3K/Akt/mTOR signaling pathway increases VEGF-C expression in lung cancer cells, thereby promoting endothelial cell proliferation. (orig.) [German] Die vorliegende Studie untersucht, ob die Strahlung die Expression von VEGF-C (vascular endothelial growth factor C) mittels Aktivierung des PI3K/Akt/mTOR-Signalwegs induziert und anschliessend die endothelialen Zellen beeinflusst. Die durch Strahlentherapie induzierte Mikrolymphgefaessdichte (MLVD) im Tumor wurde in

  16. Environmental market factors associated with electronic health record adoption among cancer hospitals.

    Science.gov (United States)

    Tarver, Will L; Menachemi, Nir

    2017-02-22

    Although recent literature has explored the relationship between various environmental market characteristics and the adoption of electronic health records (EHRs) among general, acute care hospitals, no such research currently exists for specialty hospitals, including those providing cancer care. The aim of the study was to examine the relationship between market characteristics and the adoption of EHRs among Commission on Cancer (CoC)-accredited hospitals. Secondary data on EHR adoption combined with hospital and environmental market characteristics were analyzed using logistic regression. Using the resource dependence theory, we examined how measures of munificence, complexity, and dynamism are related to the adoption of EHRs among CoC-accredited hospitals and, separately, hospitals not CoC-accredited. In a sample of 2,670 hospitals, 141 (0.05%) were academic-based CoC-accredited hospitals and 562 (21%) were community-based CoC-accredited hospitals. Measures of munificence such as cancer incidence rates (OR = 0.99, CI [0.99, 1.00], p = .020) and percentage population aged 65+ (OR = 0.99, CI [0.99, 1.00], p = .001) were negatively associated with basic EHR adoption, whereas urban location was positively associated with comprehensive EHR adoption (OR = 3.07, CI [0.89, 10.61], p = .076) for community-based CoC-accredited hospitals. Measures of complexity such as hospitals in areas with less competition were less likely to adopt a basic EHR (OR = 0.33, CI [0.19, 0.96], p = .005), whereas Medicare Managed Care penetration was positively associated with comprehensive EHR adoption (OR = 1.02, CI [1.00, 1.05], p = .070) among community-based CoC-accredited hospitals. Lastly, dynamism, measured as population change, was negatively associated with the adoption of comprehensive EHRs (OR = 0.99, CI [0.99, 1.00], p = .070) among academic-based CoC-accredited hospitals. A greater understanding of the environment's relationship to health information technology adoption in

  17. Introducing NJOY 89

    International Nuclear Information System (INIS)

    MacFarlane, R.E.

    1989-01-01

    A new version of the NJOY Nuclear Data Processing Code is described. This version is called NJOY 89, and it supports most of the features of the new ENDF-6 format including the Reich-Moore and Hybrid R-Function resonance representations, heating and damage calculations that make use of File 6 energy-angle distributions, the revised File 7 format for thermal data, and multigroup transfer matrices based on File 6. The multigroup matrices can be computed for incident neutrons or charged-particles, and for outgoing neutrons, photons, charged particles, and recoil nuclei. The MATXS output, module has been upgraded to handle charged particles in order to enable the TRANSX code to prepare multiparticle coupled sets. The plotting module can display ENDF-6 format File 6 data in both 2-d and 3-d perspective forms. In addition, some remaining problems are discussed

  18. 40 CFR 89.1003 - Prohibited acts.

    Science.gov (United States)

    2010-07-01

    ... the definition of nonroad engine in § 89.2. After the date on which a new standard takes effect... rebuilding an engine (or rebuilding a portion of an engine or engine system). Such a deviation violates paragraph (a)(3)(i) of this section. (4) For a manufacturer of a new nonroad engine subject to standards...

  19. Lysophosphatidic acid induces reactive oxygen species generation by activating protein kinase C in PC-3 human prostate cancer cells

    International Nuclear Information System (INIS)

    Lin, Chu-Cheng; Lin, Chuan-En; Lin, Yueh-Chien; Ju, Tsai-Kai; Huang, Yuan-Li; Lee, Ming-Shyue; Chen, Jiun-Hong; Lee, Hsinyu

    2013-01-01

    Highlights: •LPA induces ROS generation through LPA 1 and LPA 3 . •LPA induces ROS generation by activating PLC. •PKCζ mediates LPA-induced ROS generation. -- Abstract: Prostate cancer is one of the most frequently diagnosed cancers in males, and PC-3 is a cell model popularly used for investigating the behavior of late stage prostate cancer. Lysophosphatidic acid (LPA) is a lysophospholipid that mediates multiple behaviors in cancer cells, such as proliferation, migration and adhesion. We have previously demonstrated that LPA enhances vascular endothelial growth factor (VEGF)-C expression in PC-3 cells by activating the generation of reactive oxygen species (ROS), which is known to be an important mediator in cancer progression. Using flow cytometry, we showed that LPA triggers ROS generation within 10 min and that the generated ROS can be suppressed by pretreatment with the NADPH oxidase (Nox) inhibitor diphenylene iodonium. In addition, transfection with LPA 1 and LPA 3 siRNA efficiently blocked LPA-induced ROS production, suggesting that both receptors are involved in this pathway. Using specific inhibitors and siRNA, phospholipase C (PLC) and protein kinase C (PKC) were also suggested to participate in LPA-induced ROS generation. Overall, we demonstrated that LPA induces ROS generation in PC-3 prostate cancer cells and this is mediated through the PLC/PKC/Nox pathway

  20. Lysophosphatidic acid induces reactive oxygen species generation by activating protein kinase C in PC-3 human prostate cancer cells

    Energy Technology Data Exchange (ETDEWEB)

    Lin, Chu-Cheng; Lin, Chuan-En; Lin, Yueh-Chien [Institute of Zoology, College of Life Science, National Taiwan University, Taipei, Taiwan, ROC (China); Ju, Tsai-Kai [Instrumentation Center, National Taiwan University, Taipei, Taiwan, ROC (China); Technology Commons, College of Life Science, National Taiwan University, Taipei, Taiwan, ROC (China); Huang, Yuan-Li [Department of Biotechnology, Asia University, Taichung, Taiwan, ROC (China); Lee, Ming-Shyue [Institute of Biochemistry and Molecular Biology, College of Medicine, National Taiwan University, Taipei, Taiwan, ROC (China); Chen, Jiun-Hong [Institute of Zoology, College of Life Science, National Taiwan University, Taipei, Taiwan, ROC (China); Department of Life Science, College of Life Science, National Taiwan University, Taipei, Taiwan, ROC (China); Lee, Hsinyu, E-mail: hsinyu@ntu.edu.tw [Institute of Zoology, College of Life Science, National Taiwan University, Taipei, Taiwan, ROC (China); Department of Life Science, College of Life Science, National Taiwan University, Taipei, Taiwan, ROC (China); Center for Biotechnology, National Taiwan University, Taipei, Taiwan, ROC (China); Research Center for Developmental Biology and Regenerative Medicine, National Taiwan University, Taipei, Taiwan, ROC (China)

    2013-11-01

    Highlights: •LPA induces ROS generation through LPA{sub 1} and LPA{sub 3}. •LPA induces ROS generation by activating PLC. •PKCζ mediates LPA-induced ROS generation. -- Abstract: Prostate cancer is one of the most frequently diagnosed cancers in males, and PC-3 is a cell model popularly used for investigating the behavior of late stage prostate cancer. Lysophosphatidic acid (LPA) is a lysophospholipid that mediates multiple behaviors in cancer cells, such as proliferation, migration and adhesion. We have previously demonstrated that LPA enhances vascular endothelial growth factor (VEGF)-C expression in PC-3 cells by activating the generation of reactive oxygen species (ROS), which is known to be an important mediator in cancer progression. Using flow cytometry, we showed that LPA triggers ROS generation within 10 min and that the generated ROS can be suppressed by pretreatment with the NADPH oxidase (Nox) inhibitor diphenylene iodonium. In addition, transfection with LPA{sub 1} and LPA{sub 3} siRNA efficiently blocked LPA-induced ROS production, suggesting that both receptors are involved in this pathway. Using specific inhibitors and siRNA, phospholipase C (PLC) and protein kinase C (PKC) were also suggested to participate in LPA-induced ROS generation. Overall, we demonstrated that LPA induces ROS generation in PC-3 prostate cancer cells and this is mediated through the PLC/PKC/Nox pathway.

  1. C-Cbl reverses HER2-mediated tamoxifen resistance in human breast cancer cells.

    Science.gov (United States)

    Li, Wei; Xu, Ling; Che, Xiaofang; Li, Haizhou; Zhang, Ye; Song, Na; Wen, Ti; Hou, Kezuo; Yang, Yi; Zhou, Lu; Xin, Xing; Xu, Lu; Zeng, Xue; Shi, Sha; Liu, Yunpeng; Qu, Xiujuan; Teng, Yuee

    2018-05-02

    Tamoxifen is a frontline therapy for estrogen receptor (ER)-positive breast cancer in premenopausal women. However, many patients develop resistance to tamoxifen, and the mechanism underlying tamoxifen resistance is not well understood. Here we examined whether ER-c-Src-HER2 complex formation is involved in tamoxifen resistance. MTT and colony formation assays were used to measure cell viability and proliferation. Western blot was used to detect protein expression and protein complex formations were detected by immunoprecipitation and immunofluorescence. SiRNA was used to examine the function of HER2 in of BT474 cells. An in vivo xenograft animal model was established to examine the role of c-Cbl in tumor growth. MTT and colony formation assay showed that BT474 cells are resistant to tamoxifen and T47D cells are sensitive to tamoxifen. Immunoprecipitation experiments revealed ER-c-Src-HER2 complex formation in BT474 cells but not in T47D cells. However, ER-c-Src-HER2 complex formation was detected after overexpressing HER2 in T47D cells and these cells were more resistant to tamoxifen. HER2 knockdown by siRNA in BT474 cells reduced ER-c-Src-HER2 complex formation and reversed tamoxifen resistance. ER-c-Src-HER2 complex formation was also disrupted and tamoxifen resistance was reversed in BT474 cells by the c-Src inhibitor PP2 and HER2 antibody trastuzumab. Nystatin, a lipid raft inhibitor, reduced ER-c-Src-HER2 complex formation and partially reversed tamoxifen resistance. ER-c-Src-HER2 complex formation was disrupted by overexpression of c-Cbl but not by the c-Cbl ubiquitin ligase mutant. In addition, c-Cbl could reverse tamoxifen resistance in BT474 cells, but the ubiquitin ligase mutant had no effect. The effect of c-Cbl was validated in BT474 tumor-bearing nude mice in vivo. Immunofluorescence also revealed ER-c-Src-HER2 complex formation was reduced in tumor tissues of nude mice with c-Cbl overexpression. Our results suggested that c-Cbl can reverse tamoxifen

  2. Combined Hyperpolarized 13C-pyruvate MRS and 18F-FDG PET (HyperPET) Estimates of Glycolysis in Canine Cancer Patients

    DEFF Research Database (Denmark)

    Hansen, Adam E.; Gutte, Henrik; Holst, Pernille

    2018-01-01

    13C Magnetic Resonance Spectroscopy (MRS) using hyperpolarized 13C-labeled pyruvate as a substrate offers a measure of pyruvate-lactate interconversion and is thereby a marker of the elevated aerobic glycolysis (Warburg effect) generally exhibited by cancer cells. Here, we aim to compare hyperpol......13C Magnetic Resonance Spectroscopy (MRS) using hyperpolarized 13C-labeled pyruvate as a substrate offers a measure of pyruvate-lactate interconversion and is thereby a marker of the elevated aerobic glycolysis (Warburg effect) generally exhibited by cancer cells. Here, we aim to compare...

  3. Nicotinamide dependence of uropathogenic Escherichia coli UTI89 and application of nadB as a neutral insertion site.

    Science.gov (United States)

    Li, Zhaoli; Bouckaert, Julie; Deboeck, Francine; De Greve, Henri; Hernalsteens, Jean-Pierre

    2012-03-01

    NAD and NADP are ubiquitous in the metabolism of Escherichia coli K-12. NAD auxotrophy can be rendered by mutation in any of the three genes nadB, nadA and nadC. The nadB and nadA genes were defined as antivirulence loci in Shigella spp., as a mutation (mainly in nadB) disrupting the synthesis of quinolinate is required for virulence. Uropathogenic E. coli (UPEC) isolates from acute cystitis patients, exhibiting nicotinamide auxotrophy, were of serotype O18 : K1 : H7. E. coli UTI89, the model uropathogenic and O18 : K1 : H7 strain, requires nicotinamide or quinolinate for growth. A mutation in the nadB gene, encoding L-aspartate oxidase, was shown to be responsible for the nicotinamide requirement of UTI89. This was further confirmed by complementation of UTI89 with a recombinant plasmid harbouring the nadB gene of E. coli K-12. An Ala28Val point mutant of the recombinant plasmid failed to support the growth of UTI89 in minimal medium. This proves that the Ala28Val mutation in the NadB gene of UTI89 completely impedes de novo synthesis of nicotinamide. In spontaneous prototrophic revertants of UTI89, the nadB gene has a Val28Ala mutation. Both analyses implicate that the nicotinamide auxotrophy of UTI89 is caused by a single Ala28Val mutation in NadB. We showed that the same mutation is also present in other NAD auxotrophic E. coli O18 strains. No significant differences were observed between the virulence of isogenic NAD auxotrophic and prototrophic strains in the murine ascending urinary tract infection model. Considering these data, we applied the nadB locus as a neutral site for DNA insertions in the bacterial chromosome. We successfully restored the parental phenotype of a fimH mutant by inserting fimH, with a synthetic em7 promoter, into the nadB gene. This neutral insertion site is of significance for further research on the pathogenicity of UPEC.

  4. Salivary microRNAs as promising biomarkers for detection of esophageal cancer.

    Directory of Open Access Journals (Sweden)

    Zijun Xie

    Full Text Available BACKGROUND AND PURPOSE: Tissue microRNAs (miRNAs can detect cancers and predict prognosis. Several recent studies reported that tissue, plasma, and saliva miRNAs share similar expression profiles. In this study, we investigated the discriminatory power of salivary miRNAs (including whole saliva and saliva supernatant for detection of esophageal cancer. MATERIALS AND METHODS: By Agilent microarray, six deregulated miRNAs from whole saliva samples from seven patients with esophageal cancer and three healthy controls were selected. The six selected miRNAs were subjected to validation of their expression levels by RT-qPCR using both whole saliva and saliva supernatant samples from an independent set of 39 patients with esophageal cancer and 19 healthy controls. RESULTS: Six miRNAs (miR-10b*, miR-144, miR-21, miR-451, miR-486-5p, and miR-634 were identified as targets by Agilent microarray. After validation by RT-qPCR, miR-10b*, miR-144, and miR-451 in whole saliva and miR-10b*, miR-144, miR-21, and miR-451 in saliva supernatant were significantly upregulated in patients, with sensitivities of 89.7, 92.3, 84.6, 79.5, 43.6, 89.7, and 51.3% and specificities of 57.9, 47.4, 57.9%, 57.9, 89.5, 47.4, and 84.2%, respectively. CONCLUSIONS: We found distinctive miRNAs for esophageal cancer in both whole saliva and saliva supernatant. These miRNAs possess discriminatory power for detection of esophageal cancer. Because saliva collection is noninvasive and convenient, salivary miRNAs show great promise as biomarkers for detection of esophageal cancer in areas at high risk.

  5. Follow on colon cancer: how and when to?; Seguimiento en cancer de colon: ¿cómo y hasta cuándo?

    Energy Technology Data Exchange (ETDEWEB)

    Sarroca, C.; Della Valle, A.; Leites, A.; Denis, M.; Alonso, J.; Fresco, R.; Simonet, F.; Rodriguez, A. [Hospital Central de las Fuerzas Armadas, Ministerio de Defensa, Montevideo (Uruguay)

    2010-12-15

    There is no consensus on how monitoring should be performed curatively operated patients of colon cancer (C C). It is often it is comprehensive, causing unnecessary and considerable cost surveillance. health. The objective of this study is guidance tracking patients D C operated, making an evidence-based protocol and experience of our working group. Methods: All patients undergoing C C were retrospectively analyzed in the Central Hospital of the Armed Forces (Uruguay) between 1988 and 2003. everyone clinical control, CEA, abdominal-pelvic CT, Rx: monitoring was performed with ray, liver ultrasound, CBC, liver gram enzyme. Events interest were: local recurrence, distant polyps nat ors machi cancers, death. Results: In patients with stage I tumors detected a single event (hyperplastic polyp). In stages II-III, the majority of events were detected CEA elevation or clinically, with the imaging methods of scarce contribution. Only allowed earlier detection of 22.7% of patients with hepatic relapse, not being able to perform in most curative treatment. Special events were exceeded 5 years. Conclusions: 5 years after surgery propose to limit tracking control clinical and endoscopic every 3-5 years. In patients with polyps frequency endoscopy should conform to the characteristics thereof. We consider it unnecessary to performing imaging studies during follow-up and after CEA exceeded 5 years.

  6. Proceedings of strings, 89

    International Nuclear Information System (INIS)

    Arnowitt, R.; Bryan, R.; Duff, M.J.; Nanopoulos, D.; Pope, C.N.

    1990-01-01

    Does string theory provide us with a consistent quantum theory of gravity? Is it that Holy Grail of elementary particle physics, a Theory of Everything with embraces all the forces and particles of Nature? Even if it is, can we extract concrete predictions about our low-energy world that can be tested experimentally at the SSC and other particle accelerators? What does it have to say about the origin of the Universe and the thorny problem of the cosmological constant? Are superstring theories unique, or might the eleven-dimensional supermembrane prove equally consistent? These are just some of the question posed and debated at Strings '89

  7. Protein kinase C (PKC) isoforms in cancer, tumor promotion and tumor suppression.

    Science.gov (United States)

    Isakov, Noah

    2018-02-01

    The AGC family of serine/threonine kinases (PKA, PKG, PKC) includes more than 60 members that are critical regulators of numerous cellular functions, including cell cycle and differentiation, morphogenesis, and cell survival and death. Mutation and/or dysregulation of AGC kinases can lead to malignant cell transformation and contribute to the pathogenesis of many human diseases. Members of one subgroup of AGC kinases, the protein kinase C (PKC), have been singled out as critical players in carcinogenesis, following their identification as the intracellular receptors of phorbol esters, which exhibit tumor-promoting activities. This observation attracted the attention of researchers worldwide and led to intense investigations on the role of PKC in cell transformation and the potential use of PKC as therapeutic drug targets in cancer diseases. Studies demonstrated that many cancers had altered expression and/or mutation of specific PKC genes. However, the causal relationships between the changes in PKC gene expression and/or mutation and the direct cause of cancer remain elusive. Independent studies in normal cells demonstrated that activation of PKC is essential for the induction of cell activation and proliferation, differentiation, motility, and survival. Based on these observations and the general assumption that PKC isoforms play a positive role in cell transformation and/or cancer progression, many PKC inhibitors have entered clinical trials but the numerous attempts to target PKC in cancer has so far yielded only very limited success. More recent studies demonstrated that PKC function as tumor suppressors, and suggested that future clinical efforts should focus on restoring, rather than inhibiting, PKC activity. The present manuscript provides some historical perspectives on the tumor promoting function of PKC, reviewing some of the observations linking PKC to cancer progression, and discusses the role of PKC in the pathogenesis of cancer diseases and its

  8. Culturally-Relevant Online Cancer Education Modules Empower Alaska's Community Health Aides/Practitioners to Disseminate Cancer Information and Reduce Cancer Risk.

    Science.gov (United States)

    Cueva, Katie; Revels, Laura; Cueva, Melany; Lanier, Anne P; Dignan, Mark; Viswanath, K; Fung, Teresa T; Geller, Alan C

    2017-04-12

    To address a desire for timely, medically accurate cancer education in rural Alaska, ten culturally relevant online learning modules were developed with, and for, Alaska's Community Health Aides/Practitioners (CHA/Ps). The project was guided by the framework of Community-Based Participatory Action Research, honored Indigenous Ways of Knowing, and was informed by Empowerment Theory. A total of 428 end-of-module evaluation surveys were completed by 89 unique Alaska CHA/Ps between January and December 2016. CHA/Ps shared that as a result of completing the modules, they were empowered to share cancer information with their patients, families, friends, and communities, as well as engage in cancer risk reduction behaviors such as eating healthier, getting cancer screenings, exercising more, and quitting tobacco. CHA/Ps also reported the modules were informative and respectful of their diverse cultures. These results from end-of-module evaluation surveys suggest that the collaboratively developed, culturally relevant, online cancer education modules have empowered CHA/Ps to reduce cancer risk and disseminate cancer information. "brought me to tears couple of times, and I think it will help in destroying the silence that surrounds cancer".

  9. 40 CFR 600.006-89 - Data and information requirements for fuel economy vehicles.

    Science.gov (United States)

    2010-07-01

    ... fuel economy vehicles. 600.006-89 Section 600.006-89 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) ENERGY POLICY FUEL ECONOMY AND CARBON-RELATED EXHAUST EMISSIONS OF MOTOR VEHICLES Fuel Economy Regulations for 1977 and Later Model Year Automobiles-General Provisions § 600.006-89 Data and...

  10. State borders in ETRS89 coordinates – reality or fiction ?

    Directory of Open Access Journals (Sweden)

    Jiří Poláček

    2015-12-01

    Full Text Available Common unique ETRS89 coordinates of the state boundaries are crucial for cross-border data harmonization for international projects. In the frame of European Location Framework (ELF project Czech Office for Surveying, Mapping and Cadastre (ČÚZK cooperates with Poland on egde-matching on the state border. During the preliminary phase of the project was some difficulty identified. If the state boundary is measured and administered in the national coordinate system, the accuracy of the transformation into the ETRS89 is influenced by discrepancies of the local trigonometric network, which results in two slightly different state boundaries. Final solution for Europe – international treaties on the state borders based on the ETRS89 coordinates – is necessary, but it will take years.

  11. Impact of neoadjuvant treatment on total mesorectal excision for ultra-low rectal cancers

    Directory of Open Access Journals (Sweden)

    Fan Joe FM

    2010-03-01

    Full Text Available Abstract Background This study reviewed the impact of pre-operative chemoradiotherapy or post-operative chemotherapy and/or radiotherapy on total mesorectal excision (TME for ultralow rectal cancers that required either low anterior resection with peranal coloanal anastomosis or abdomino-perineal resection (APR. We examined surgical complications, local recurrence and survival. Methods Of the 1270 patients who underwent radical resection for rectal cancer from 1994 till 2007, 180 with tumors within 4 cm with either peranal coloanal anastomosis or APR were analyzed. Patients were compared in groups that had surgery only (Group A, pre-operative chemoradiotherapy (Group B, and post-operative therapy (Group C. Results There were 115 males and the mean age was 65.43 years (range 30-89. APR was performed in 134 patients while 46 had a sphincter-preserving resection with peranal coloanal anastomosis. The mean follow-up period was 52.98 months (range: 0.57 to 178.9. There were 69, 58 and 53 patients in Groups A, B, and C, respectively. Nine patients in Group B could go on to have sphincter-saving rectal resection. The overall peri-operative complication rate was 43.4% in Group A vs. 29.3% in Group B vs. 39.6% in Group C, respectively. The local recurrence rate was significantly lower in Group B (8.6.9% vs. 21.7% in Group A vs. 33.9% in Group C p . The 5-year cancer-specific survival rates for Group A was 49.3%, Group B was 69.9% and Group C was 38.8% (p = 0.14. Conclusion Pre-operative chemoradiation in low rectal cancer is not associated with a higher incidence of peri-operative complications and its benefits may include reduction local recurrence.

  12. Galectin-3 and Beclin1/Atg6 genes in human cancers: using cDNA tissue panel, qRT-PCR, and logistic regression model to identify cancer cell biomarkers.

    Directory of Open Access Journals (Sweden)

    Halliday A Idikio

    Full Text Available Cancer biomarkers are sought to support cancer diagnosis, predict cancer patient response to treatment and survival. Identifying reliable biomarkers for predicting cancer treatment response needs understanding of all aspects of cancer cell death and survival. Galectin-3 and Beclin1 are involved in two coordinated pathways of programmed cell death, apoptosis and autophagy and are linked to necroptosis/necrosis. The aim of the study was to quantify galectin-3 and Beclin1 mRNA in human cancer tissue cDNA panels and determine their utility as biomarkers of cancer cell survival.A panel of 96 cDNAs from eight (8 different normal and cancer tissue types were used for quantitative real-time polymerase chain reaction (qRT-PCR using ABI7900HT. Miner2.0, a web-based 4- and 3-parameter logistic regression software was used to derive individual well polymerase chain reaction efficiencies (E and cycle threshold (Ct values. Miner software derived formula was used to calculate mRNA levels and then fold changes. The ratios of cancer to normal tissue levels of galectin-3 and Beclin1 were calculated (using the mean for each tissue type. Relative mRNA expressions for galectin-3 were higher than for Beclin1 in all tissue (normal and cancer types. In cancer tissues, breast, kidney, thyroid and prostate had the highest galectin-3 mRNA levels compared to normal tissues. High levels of Beclin1 mRNA levels were in liver and prostate cancers when compared to normal tissues. Breast, kidney and thyroid cancers had high galectin-3 levels and low Beclin1 levels.Galectin-3 expression patterns in normal and cancer tissues support its reported roles in human cancer. Beclin1 expression pattern supports its roles in cancer cell survival and in treatment response. qRT-PCR analysis method used may enable high throughput studies to generate molecular biomarker sets for diagnosis and predicting cancer treatment response.

  13. Aspirin therapy reduces the ability of platelets to promote colon and pancreatic cancer cell proliferation: Implications for the oncoprotein c-MYC

    Science.gov (United States)

    Sylman, Joanna L.; Ngo, Anh T. P.; Pang, Jiaqing; Sears, Rosalie C.; Williams, Craig D.; McCarty, Owen J. T.

    2017-01-01

    Aspirin, an anti-inflammatory and antithrombotic drug, has become the focus of intense research as a potential anticancer agent owing to its ability to reduce tumor proliferation in vitro and to prevent tumorigenesis in patients. Studies have found an anticancer effect of aspirin when used in low, antiplatelet doses. However, the mechanisms through which low-dose aspirin works are poorly understood. In this study, we aimed to determine the effect of aspirin on the cross talk between platelets and cancer cells. For our study, we used two colon cancer cell lines isolated from the same donor but characterized by different metastatic potential, SW480 (nonmetastatic) and SW620 (metastatic) cancer cells, and a pancreatic cancer cell line, PANC-1 (nonmetastatic). We found that SW480 and PANC-1 cancer cell proliferation was potentiated by human platelets in a manner dependent on the upregulation and activation of the oncoprotein c-MYC. The ability of platelets to upregulate c-MYC and cancer cell proliferation was reversed by an antiplatelet concentration of aspirin. In conclusion, we show for the first time that inhibition of platelets by aspirin can affect their ability to induce cancer cell proliferation through the modulation of the c-MYC oncoprotein. PMID:27903583

  14. Vitamin C transporter gene (SLC23A1 and SLC23A2) polymorphisms, plasma vitamin C levels, and gastric cancer risk in the EPIC cohort

    NARCIS (Netherlands)

    Duell, E.J.; Lujan-Barroso, L.; Llivina, C.; Munoz, X.; Jenab, M.; Boutron-Ruault, M.C.; Clavel-Chapelon, F.; Racine, A.; Boeing, H; Buijsse, B.; Canzian, F.; Johnson, T.; Dalgard, C.; Overvad, K.; Tjonneland, A.; Olsen, A.; Sanchez, S.C.; Sanchez-Cantalejo, E.; Huerta, J.M.; Ardanaz, E.; Dorronsoro, M.; Khaw, K.T.; Travis, R.C.; Trichopoulou, A.; Trichopoulos, D.; Rafnsson, S.; Palli, D.; Sacerdote, C.; Tumino, R.; Panico, S; Grioni, S.; Bueno-de-Mesquita, H.B.; Ros, M.M.; Numans, M.E.; Peeters, P.H.; Johansen, D.; Lindkvist, B.; Johansson, M.; Johansson, I.; Skeie, G.; Weiderpass, E; Duarte-Salles, T.; Stenling, R.; Riboli, E.; Sala, N.; Gonzalez, CA

    2013-01-01

    Vitamin C is known to protect mucosal tissues from oxidative stress and inhibit nitrosamine formation in the stomach. High consumption of fruits, particularly citrus, and higher circulating vitamin C concentrations may be inversely associated with gastric cancer (GC) risk. We investigated 20

  15. Vitamin C transporter gene (SLC23A1 and SLC23A2) polymorphisms, plasma vitamin C levels, and gastric cancer risk in the EPIC cohort

    DEFF Research Database (Denmark)

    Duell, Eric J; Lujan-Barroso, Leila; Llivina, Claudia

    2013-01-01

    Vitamin C is known to protect mucosal tissues from oxidative stress and inhibit nitrosamine formation in the stomach. High consumption of fruits, particularly citrus, and higher circulating vitamin C concentrations may be inversely associated with gastric cancer (GC) risk. We investigated 20 poly...

  16. Complement component 1, q subcomponent binding protein (C1QBP) in lipid rafts mediates hepatic metastasis of pancreatic cancer by regulating IGF-1/IGF-1R signaling.

    Science.gov (United States)

    Shi, Haojun; Fang, Winston; Liu, Minda; Fu, Deliang

    2017-10-01

    Pancreatic cancer shows a remarkable predilection for hepatic metastasis. Complement component 1, q subcomponent binding protein (C1QBP) can mediate growth factor-induced cancer cell chemotaxis and distant metastasis by activation of receptor tyrosine kinases. Coincidentally, insulin-like growth factor-1 (IGF-1) derived from the liver and cancer cells itself has been recognized as a critical inducer of hepatic metastasis. However, the mechanism underlying IGF-1-dependent hepatic metastasis of pancreatic cancer, in which C1QBP may be involved, remains unknown. In the study, we demonstrated a significant association between C1QBP expression and hepatic metastasis in patients with pancreatic cancer. IGF-1 induced the translocation of C1QBP from cytoplasm to lipid rafts and further drove the formation of CD44 variant 6 (CD44v6)/C1QBP complex in pancreatic cancer cells. C1QBP interacting with CD44v6 in lipid rafts promoted phosphorylation of IGF-1R and thus activated downstream PI3K and MAPK signaling pathways which mediated metastatic potential of pancreatic cancer cells including proliferation, apoptosis, invasion, adhesion and energy metabolism. Furthermore, C1QBP knockdown suppressed hepatic metastasis of pancreatic cancer cells in nude mice. We therefore conclude that C1QBP in lipid rafts serves a key regulator of IGF-1/IGF-1R-induced hepatic metastasis from pancreatic cancer. Our findings about C1QBP in lipid rafts provide a novel strategy to block IGF-1/IGF-1R signaling in pancreatic cancer and a reliable premise for more efficient combined modality therapies. © 2017 UICC.

  17. Overexpression of c-erbB-2 and loss of p16 have molecular diagnostic relevance but no prognostic value in lung cancer.

    Science.gov (United States)

    Feng, Xiao-li; Li, Ling; Gao, Yan-ning; Zhang, Jian-jun; Xiao, Ting; Ying, Jian-ming; Gao, Ji-dong; Sun, Yun-tian; Cheng, Shu-jun

    2011-03-01

    This study was designed to evaluate the expression of C-erbB-2 and p16 in lung cancers using tissue microarray technology and to determine their clinical and pathological significance. Immunohistochemical C-erbB-2 and p16 expressions and their associations with clinical and pathological features were analyzed in two tissue microarrays. The membranous and cytoplasmic expression rates of C-erbB-2 were 40.5 and 66.5% in non-small cell lung cancers (NSCLCs), and 0 and 9.5% in small cell lung cancers (SCLCs), respectively. The nuclear and cytoplasmic expression rates of p16 were 11.5 and 32.2% in NSCLs, and 45 and 80% in SCLCs, respectively. The cytoplasmic expression of both C-erbB-2 and p16 was more frequent than the membranous expression of C-erbB-2 and the nuclear expression of p16. The rates of overexpression of C-erbB-2 and loss of p16 expression were significantly higher in NSCLCs than in SCLCs (P < 0.05). Neither C-erbB-2 nor p16 expression was significantly associated with age, tumor grade or stage, presence of lymph node metastasis or survival duration. The abnormal expressions of p16 and C-erbB-2 may play a role in the progression of lung cancers. The variations in the expression patterns of C-erbB-2 and p16 between NSCLCs and SCLCs may aid the molecular classification of lung cancer. The abnormal expression of p16 may be involved in the development of NSCLCs, and the overexpression of C-erbB-2 in NSCLCs indicates that it can be a candidate target for gene therapy.

  18. Relationship between miR-146a rs2910164 (G>C) Polymorphism and Digestive System Cancer Susceptibility: A Meta-Analysis.

    Science.gov (United States)

    Xiong, Xin; Yan, Junfeng; Li, Linghua; Li, Yun; Cao, Yi; Tu, Yi; Mei, Jinhong

    2017-08-01

    MicroRNAs (miRNAs) are identified negatively regulating gene expression and acting as oncogenes or tumor suppressors in tumorigenesis. The association between miR-146a rs2910164 (G>C) polymorphism and susceptibility to digestive system cancers was contradictory and inconsistent in previously published studies. Presently, we performed a comprehensive literature retrieve on PubMed, Web of Science, Embase, Wanfang and CNKI databases to identify all relevant studies published before July 30, 2016. Odds ratio (OR) and 95% confidential interval (95%CI) were used to calculate the relationship between miR-146a rs2910164 (G>C) polymorphism and digestive system cancers susceptibility. Finally, a total of 45 publications comprising 47 separate case-control studies were enrolled in the present updated meta-analysis including 20,281 cases and 26,099 controls. However, no significant association was uncovered for miR-146a rs2910164 polymorphism and digestive system cancers susceptibility in all the genetic models. Moreover, in the stratification analyses by cancer type, the source of control, ethnicity and Hardy-Weinberg Equilibrium (HWE) status, we also revealed a negative result. To conclude, our work suggests that miR-146a rs2910164 (G>C) polymorphism is not a susceptibility factor for digestive system cancers. © 2017 by the Association of Clinical Scientists, Inc.

  19. 40 CFR 89.1009 - What special provisions apply to branded engines?

    Science.gov (United States)

    2010-07-01

    ... 40 Protection of Environment 20 2010-07-01 2010-07-01 false What special provisions apply to branded engines? 89.1009 Section 89.1009 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY... branded engines? A manufacturer identifying the name and trademark of another company on the emission...

  20. 40 CFR 89.123 - Amending the application and certificate of conformity.

    Science.gov (United States)

    2010-07-01

    ... certificate of conformity. 89.123 Section 89.123 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY... of conformity. (a) The manufacturer of nonroad compression-ignition engines must notify the... be made to a product line covered by a certificate of conformity. This notification must include a...