WorldWideScience

Sample records for cancer radioimmunotherapy development

  1. Alpha-radioimmunotherapy: a review of recent developments

    International Nuclear Information System (INIS)

    The use of heavy particles in the treatment of cancer is increasing remarkably, whether with external radiation or using a vector such as an antibody in radioimmunotherapy. Recent pre-clinical and clinical developments of alpha-radioimmunotherapy have provided more interesting information in parallel of the use of high Linear Energy Transfer (Let) external irradiation. This review aims at presenting recent advances of this therapeutic approach, and at detailing the biological specificities of this kind of radiation. (authors)

  2. Radioimmunotherapy: Development of an effective approach

    International Nuclear Information System (INIS)

    Goals of this program are to answer the fundamental scientific questions for the development of an effective approach for delivering radiation therapy to cancer on antibody-based radiopharmaceuticals. The following list consists of highlights of developments from our program: documented therapeutic response of lymphoma in patients receiving radioimmunotherapy; development and application of quantitative radionuclide imaging techniques for therapy planning and dosimetry calculations; multicompartmental modeling and analysis of the in vivo MoAb kinetics in patients; a MoAb macrocycle chelate for Cu-67: development, production, in vitro and in vivo testing; NMR analysis of immunoradiotherapeutic effects on the metabolism of lymphoma; analysis of the variable molecular characteristics of the MoAb radiopharmaceutical, and their significance; in vivo studies in mice and patients of the metabolism of radioiodinated MoAb as well as In-111 CITC MoAb; and biodistribution of Cu-67 TETA MoAb in nude mice with human lymphoma

  3. Radioimmunotherapy: Development of an effective approach

    Energy Technology Data Exchange (ETDEWEB)

    1987-01-01

    Goals of this program are to answer the fundamental scientific questions for the development of an effective approach for delivering radiation therapy to cancer on antibody-based radiopharmaceuticals. The following list consists of highlights of developments from our program: documented therapeutic response of lymphoma in patients receiving radioimmunotherapy; development and application of quantitative radionuclide imaging techniques for therapy planning and dosimetry calculations; multicompartmental modeling and analysis of the in vivo MoAb kinetics in patients; a MoAb macrocycle chelate for Cu-67: development, production, in vitro and in vivo testing; NMR analysis of immunoradiotherapeutic effects on the metabolism of lymphoma; analysis of the variable molecular characteristics of the MoAb radiopharmaceutical, and their significance; in vivo studies in mice and patients of the metabolism of radioiodinated MoAb as well as In-111 CITC MoAb; and biodistribution of Cu-67 TETA MoAb in nude mice with human lymphoma.

  4. Radioimmunotherapy: Opportunities, obstacles and challenges, with special reference to developing countries

    International Nuclear Information System (INIS)

    The targeting characteristics of, combined with the ease of radionuclide conjugation to, monoclonal antibodies makes them ideally suited for the selective delivery of potentially cytotoxic radioactivity to tumour. While early murine monoclonal antibodies were immunogenic, precluding repeat administration, genetic engineering has made possible the development of less immunogenic molecules, including fragments that can be grown in bacterial systems at relatively low cost. It is therefore currently feasible to produce relatively non-immunogenic tumour targeting antibody molecules at a reasonable cost, permitting their application in developing countries. As with chemotherapy, the utility of radioimmunotherapy has been most evident in lymphoma and leukemia. Progress in solid tumours has been exciting but slow. As with thyroid cancer therapy, the most utilized radionuclide in radioimmunotherapy has been iodine-131. The use of radioimmunotherapy as first- or second-line therapy in lymphoma and leukemia is being studied, and it appears likely that radioimmunotherapy could be a suitable, lower-cost alternative to chemotherapy in the treatment of these disorders, especially in developing countries. The cost-benefit of radioimmunotherapy compared to chemotherapy is especially stark when the cost of treating complications of chemotherapy is taken into account. Radioimmunotherapy as cost-effective therapy in developing countries is therefore feasible and has tremendous potential. This review will highlight milestones and pitfalls; suggest guidelines for future development; and outline potential clinical utility for radioimmunotherapy in developing countries. (author)

  5. Radioimmunotherapy: Development of an effective approach

    International Nuclear Information System (INIS)

    We plan to extend our success in treating B cell malignancies with 131I labeled Lym-1 by a major effort in therapy with 67Cu Lym-1. Yttrium-90 labeled by a macrocycle, DOTA will be studied in patients as a continuation of the 111In-BAD (DOTA) Lym-1 studies. Excellent images and pharmacokinetics of the 111In-BAD(DOTA)-Lym-1 studies. Lymphomas and related diseases represent a special case for radioimmunotherapy because of their documented radiosensitivity and immunodeficiency, and thus offer a unique opportunity to conduct therapeutic feasibility studies in a responsive human model. Using marine and chimeric L6 and other MoAb to breast cancer, we have applied the strategies that were developed in taking Lym-1 antibody from the bench to the patient. We have examined a number of monoclonal antibodies for treatment of breast cancer and chose chimeric L6 for prototype studies because of certain characteristics. The chemistry of attachment of conjugates to antibodies and their impact on immunological targeting biological activities (cytotoxicity), metabolic fate, and therapeutic index will continue to be a major strength and function of this program. This grant has supported the conception, synthesis, and development of the first macrocylic, bifunctional chelating agent TETA (6-p-nitrobenzyl-1,4,8,11-tetraazatetradecane-N,N',N double-prime, N'double-prime-tetraacetic acid and its derivatives, including Lym-1-2IT-BAT), for use in Cu-67-based radioimmunodiagnosis and therapy. This work has led to the further development of several new macrocylic bifunctional chelating agents for copper, indium, yttrium and other metals. In addition, successful Cu-67 labelings of Lym-1-2IT-BAT for human radiopharmaceutical have shown patient pharmacokinetics of 67Cu-BAT(TETA)-Lym-1 with promising therapeutic dosimetry

  6. Development of a radioscandium immunoconjugate for radioimmunotherapy

    Energy Technology Data Exchange (ETDEWEB)

    Moghaddam-Banaem, L.; Jalilian, A.R.; Pourjavid, M.R.; Radfar, E.; Bahrami-Samani, A.; Yavari, K.; Mazidi, M.; Ghannadi-Maragheh, M. [Nuclear Science and Technology Research Institute (NSTRI), Tehran (IR). Radiopharmaceutical Research and Development Lab. (RRDL)

    2012-07-01

    Developing monoclonal antibodies labeled with beta-emitters has led to the introduction of important agents in radioimmunotherapy. In this work, Sc-46 chloride was obtained by thermal neutron activation flux of natural metallic scandium sample followed by dissolution in acidic media (radionuclidic purity via beta and gamma ray spectroscopy, 99.9; radiochemical purity via ITLC, > 99%) and used in radiolabeling of rituximab after conjugation with DOTA-NHS-ester. The specific activity was however not high. The conjugates were purified by molecular filtration and used in the radiolabeling. The radiochemical purity (ITLC), stability studies (ITLC and size exclusion chromatography), determination of average number of DOTA conjugated per mAb (chelate: antibody ratio, 5.8:1) and gel electrophoresis of [{sup 46}Sc]Sc-DOTA-anti-CD20 were determined followed by biodistribution studies for {sup 46}Sc and [{sup 46}Sc]Sc-DOTA-anti-CD20 i n wild type rats up to 72 h. The binding of the radiolabeled antibody was showed to be 60% on Raji cells. The final compound was stable in presence of PBS at 37 C and room temperature. The accumulation of the radiolabeled antibody in liver, spleen, kidney, heart and other tissues demonstrates a pattern similar to the other radiolabeled anti-CD20 immunoconjugates. The present study shows the possibility of antibody labeling for future use in radioimmunotherapy by {sup 47}Sc. (orig.)

  7. Repeated Intraperitoneal alpha-Radioimmunotherapy of Ovarian Cancer in Mice

    DEFF Research Database (Denmark)

    Elgqvist, Jörgen; Andersson, Håkan; Jensen, Holger; Kahu, Helena; Lindegren, Sture; Warnhammar, Elisabet; Hultborn, Ragnar

    2010-01-01

    The aim of this study was to investigate the therapeutic efficacy of alpha-radioimmunotherapy of ovarian cancer in mice using different fractionated treatment regimens. The study was performed using the monoclonal antibody MX35 F(ab')(2) labeled with the alpha-particle emitter (211)At. Methods...

  8. Radioimmunotherapy: Development of an effective approach. Progress report, 1987

    Energy Technology Data Exchange (ETDEWEB)

    1987-12-31

    Goals of this program are to answer the fundamental scientific questions for the development of an effective approach for delivering radiation therapy to cancer on antibody-based radiopharmaceuticals. The following list consists of highlights of developments from our program: documented therapeutic response of lymphoma in patients receiving radioimmunotherapy; development and application of quantitative radionuclide imaging techniques for therapy planning and dosimetry calculations; multicompartmental modeling and analysis of the in vivo MoAb kinetics in patients; a MoAb macrocycle chelate for Cu-67: development, production, in vitro and in vivo testing; NMR analysis of immunoradiotherapeutic effects on the metabolism of lymphoma; analysis of the variable molecular characteristics of the MoAb radiopharmaceutical, and their significance; in vivo studies in mice and patients of the metabolism of radioiodinated MoAb as well as In-111 CITC MoAb; and biodistribution of Cu-67 TETA MoAb in nude mice with human lymphoma.

  9. Intraperitoneal radioimmunotherapy in treating peritoneal carcinomatosis of colon cancer in mice compared with systemic radioimmunotherapy

    International Nuclear Information System (INIS)

    Peritoneal spread is one of major causes of mortality in colorectal cancer patients. In the current investigation, the efficacy of radio-immunotherapy (RIT) with intraperitoneal (i.p.) administration of an anti-colorectal cancer IgG1, 131I-A7, was compared to that with intravenous (i.v.) administration in BALB/c female mice bearing peritoneal nodules of LS180 human colon cancer cells, at the same toxicity level. Distribution of either i.p. or i.v. administered 131I-A7 and i.p. administered irrelevant 131I -HPMS-1 was assessed. Based on the results of toxicity determination at increments of 2 MBq and estimated dosimetry, an i.p. dose of 11 MBq and an i.v. dose of 9 MBq were chosen for treatment. Mice were monitored for long-term survival: untreated mice (n=11), mice undergoing i.p. RIT with 131I-A7 (n=11), mice undergoing i.v. RIT with 131I-A7 (n=11) and mice undergoing non-specific i.p. RIT with 131I-HPMS-1 (n=5). Intraperitoneal injection of 131I-A7 produced faster and greater tumor accumulation than i.v. injection: 34.2±16.5% of the injected dose per g (% ID/g) and 11.1±3.6% ID/g at 2 h, respectively (P131I-HPMS-1 did not show specific accumulation. Non-specific RIT with 131I-HPMS-1 (mean survival, 26.0±2.5 days) did not affect the survival as compared to no treatment (26.7±1.9 days). Intravenous RIT with 131I-A7 prolonged the survival of mice to 32.8±1.8 days (P131I-A7 improved the survival more significantly and attained cure in 2 of 11 mice (P<0.05 vs. i.v. RIT). In conclusion, i.p. RIT is more beneficial in treating peritoneal carcinomatosis of colon cancer than i.v. RIT in a murine model. (author)

  10. Activation of PDGFr-β Signaling Pathway after Imatinib and Radioimmunotherapy Treatment in Experimental Pancreatic Cancer

    OpenAIRE

    Elizabeth Mack; Michio Abe; Zbigniew P. Kortylewicz; Enke, Charles A.; Janina Baranowska-Kortylewicz

    2011-01-01

    Pancreatic cancer does not respond to a single-agent imatinib therapy. Consequently, multimodality treatments are contemplated. Published data indicate that in colorectal cancer, imatinib and radioimmunotherapy synergize to delay tumor growth. In pancreatic cancer, the tumor response is additive. This disparity of outcomes merited further studies because interactions between these modalities depend on the imatinib-induced reduction of the tumor interstitial fluid pressure. The examination of ...

  11. SU-E-J-03: A Comprehensive Comparison Between Alpha and Beta Emitters for Cancer Radioimmunotherapy

    Energy Technology Data Exchange (ETDEWEB)

    Huang, C.Y. [University of Sydney, Camperdown, NSW (Australia); Guatelli, S [University of Wollongong, Wollongong, NSW (Australia); Oborn, B [Illawarra Cancer Care Centre, Wollongong, NSW (Australia); Allen, B [University of Western Sydney, Liverpool, NSW (Australia)

    2014-06-01

    Purpose: The purpose of this study is to perform a comprehensive comparison of the therapeutic efficacy and cytotoxicity of alpha and beta emitters for Radioimmunotherapy (RIT). For each stage of cancer development, specific models were built for the separate objectives of RIT to be addressed:a) kill isolated cancer cells in transit in the lymphatic and vascular circulation,b) regress avascular cell clusters,c) regress tumor vasculature and tumors. Methods: Because of the nature of short range, high LET alpha and long energy beta radiation and heterogeneous antigen expression among cancer cells, the microdosimetric approach is essential for the RIT assessment. Geant4 based microdosimetric models are developed for the three different stages of cancer progression: cancer cells, cell clusters and tumors. The energy deposition, specific energy resulted from different source distribution in the three models was calculated separately for 4 alpha emitting radioisotopes ({sup 211}At, {sup 213}Bi, {sup 223}Ra and {sup 225}Ac) and 6 beta emitters ({sup 32}P, {sup 33}P, {sup 67}Cu, {sup 90}Y, {sup 131}I and {sup 177}Lu). The cell survival, therapeutic efficacy and cytotoxicity are determined and compared between alpha and beta emitters. Results: We show that internal targeted alpha radiation has advantages over beta radiation for killing isolated cancer cells, regressing small cell clusters and also solid tumors. Alpha particles have much higher dose specificity and potency than beta particles. They can deposit 3 logs more dose than beta emitters to single cells and solid tumor. Tumor control probability relies on deep penetration of radioisotopes to cancer cell clusters and solid tumors. Conclusion: The results of this study provide a quantitative understanding of the efficacy and cytotoxicity of RIT for each stage of cancer development.

  12. SU-E-J-03: A Comprehensive Comparison Between Alpha and Beta Emitters for Cancer Radioimmunotherapy

    International Nuclear Information System (INIS)

    Purpose: The purpose of this study is to perform a comprehensive comparison of the therapeutic efficacy and cytotoxicity of alpha and beta emitters for Radioimmunotherapy (RIT). For each stage of cancer development, specific models were built for the separate objectives of RIT to be addressed:a) kill isolated cancer cells in transit in the lymphatic and vascular circulation,b) regress avascular cell clusters,c) regress tumor vasculature and tumors. Methods: Because of the nature of short range, high LET alpha and long energy beta radiation and heterogeneous antigen expression among cancer cells, the microdosimetric approach is essential for the RIT assessment. Geant4 based microdosimetric models are developed for the three different stages of cancer progression: cancer cells, cell clusters and tumors. The energy deposition, specific energy resulted from different source distribution in the three models was calculated separately for 4 alpha emitting radioisotopes (211At, 213Bi, 223Ra and 225Ac) and 6 beta emitters (32P, 33P, 67Cu, 90Y, 131I and 177Lu). The cell survival, therapeutic efficacy and cytotoxicity are determined and compared between alpha and beta emitters. Results: We show that internal targeted alpha radiation has advantages over beta radiation for killing isolated cancer cells, regressing small cell clusters and also solid tumors. Alpha particles have much higher dose specificity and potency than beta particles. They can deposit 3 logs more dose than beta emitters to single cells and solid tumor. Tumor control probability relies on deep penetration of radioisotopes to cancer cell clusters and solid tumors. Conclusion: The results of this study provide a quantitative understanding of the efficacy and cytotoxicity of RIT for each stage of cancer development

  13. Activation of PDGFr-β Signaling Pathway after Imatinib and Radioimmunotherapy Treatment in Experimental Pancreatic Cancer

    International Nuclear Information System (INIS)

    Pancreatic cancer does not respond to a single-agent imatinib therapy. Consequently, multimodality treatments are contemplated. Published data indicate that in colorectal cancer, imatinib and radioimmunotherapy synergize to delay tumor growth. In pancreatic cancer, the tumor response is additive. This disparity of outcomes merited further studies because interactions between these modalities depend on the imatinib-induced reduction of the tumor interstitial fluid pressure. The examination of human and murine PDGFr-β/PDGF-B pathways in SW1990 pancreatic cancer xenografts revealed that the human branch is practically dormant in untreated tumors but the insult on the stromal component produces massive responses of human cancer cells. Inhibition of the stromal PDGFr-β with imatinib activates human PDGFr-β/PDGF-B signaling loop, silent in untreated xenografts, via an apparent paracrine rescue pathway. Responses are treatment-and time-dependent. Soon after treatment, levels of human PDGFr-β, compared to untreated tumors, are 3.4×, 12.4×, and 5.7× higher in imatinib-, radioimmunotherapy + imatinib-, and radioimmunotherapy-treated tumors, respectively. A continuous 14-day irradiation of imatinib-treated xenografts reduces levels of PDGFr-β and phosphorylated PDGFr-β by 5.3× and 4×, compared to earlier times. Human PDGF-B is upregulated suggesting that the survival signaling via the autocrine pathway is also triggered after stromal injury. These findings indicate that therapies targeting pancreatic cancer stromal components may have unintended mitogenic effects and that these effects can be reversed when imatinib is used in conjunction with radioimmunotherapy

  14. Activation of PDGFr-β Signaling Pathway after Imatinib and Radioimmunotherapy Treatment in Experimental Pancreatic Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Abe, Michio [Minamata City Hospital and Medical Center, Minamata City, Kumamoto 867 (Japan); Kortylewicz, Zbigniew P.; Enke, Charles A.; Mack, Elizabeth; Baranowska-Kortylewicz, Janina, E-mail: jbaranow@unmc.edu [Department of Radiation Oncology, J. Bruce Henriksen Cancer Research Laboratories, University of Nebraska Medical Center, Omaha, NE 68198 (United States)

    2011-05-25

    Pancreatic cancer does not respond to a single-agent imatinib therapy. Consequently, multimodality treatments are contemplated. Published data indicate that in colorectal cancer, imatinib and radioimmunotherapy synergize to delay tumor growth. In pancreatic cancer, the tumor response is additive. This disparity of outcomes merited further studies because interactions between these modalities depend on the imatinib-induced reduction of the tumor interstitial fluid pressure. The examination of human and murine PDGFr-β/PDGF-B pathways in SW1990 pancreatic cancer xenografts revealed that the human branch is practically dormant in untreated tumors but the insult on the stromal component produces massive responses of human cancer cells. Inhibition of the stromal PDGFr-β with imatinib activates human PDGFr-β/PDGF-B signaling loop, silent in untreated xenografts, via an apparent paracrine rescue pathway. Responses are treatment-and time-dependent. Soon after treatment, levels of human PDGFr-β, compared to untreated tumors, are 3.4×, 12.4×, and 5.7× higher in imatinib-, radioimmunotherapy + imatinib-, and radioimmunotherapy-treated tumors, respectively. A continuous 14-day irradiation of imatinib-treated xenografts reduces levels of PDGFr-β and phosphorylated PDGFr-β by 5.3× and 4×, compared to earlier times. Human PDGF-B is upregulated suggesting that the survival signaling via the autocrine pathway is also triggered after stromal injury. These findings indicate that therapies targeting pancreatic cancer stromal components may have unintended mitogenic effects and that these effects can be reversed when imatinib is used in conjunction with radioimmunotherapy.

  15. Fractionated Radioimmunotherapy With 90Y-Clivatuzumab Tetraxetan and Low-Dose Gemcitabine Is Active in Advanced Pancreatic Cancer

    Science.gov (United States)

    Ocean, Allyson J.; Pennington, Kenneth L.; Guarino, Michael J.; Sheikh, Arif; Bekaii-Saab, Tanios; Serafini, Aldo N.; Lee, Daniel; Sung, Max W.; Gulec, Seza A.; Goldsmith, Stanley J.; Manzone, Timothy; Holt, Michael; O’Neil, Bert H.; Hall, Nathan; Montero, Alberto J.; Kauh, John; Gold, David V.; Horne, Heather; Wegener, William A.; Goldenberg, David M.

    2014-01-01

    BACKGROUND It has been demonstrated that the humanized clivatuzumab tetraxetan (hPAM4) antibody targets pancreatic ductal carcinoma selectively. After a trial of radioimmunotherapy that determined the maximum tolerated dose of single-dose yttrium-90-labeled hPAM4 (90Y-hPAM4) and produced objective responses in patients with advanced pancreatic ductal carcinoma, the authors studied fractionated radioimmunotherapy combined with low-dose gemcitabine in this disease. METHODS Thirty-eight previously untreated patients (33 patients with stage IV disease and 5 patients with stage III disease) received gemcitabine 200 mg/m2 weekly for 4 weeks with 90Y-hPAM4 given weekly in Weeks 2, 3, and 4 (cycle 1), and the same cycle was repeated in 13 patients (cycles 2–4). In the first part of the study, 19 patients received escalating weekly 90Y doses of 6.5 mCi/m2, 9.0 mCi/m2, 12.0 mCi/m2, and 15.0 mCi/m2. In the second portion, 19 additional patients received weekly doses of 9.0 mCi/m2 or 12.0 mCi/m2. RESULTS Grade 3/4 thrombocytopenia or neutropenia (according to version 3.0 of the National Cancer Institute’s Common Terminology Criteria for Adverse Events) developed in 28 of 38 patients after cycle 1 and in all retreated patients; no grade >3 nonhematologic toxicities occurred. Fractionated dosing of cycle 1 allowed almost twice the radiation dose compared with single-dose radioimmunotherapy. The maximum tolerated dose of 90Y-hPAM4 was 12.0 mCi/m2 weekly for 3 weeks for cycle 1, with ≤9.0 mCi/m2 weekly for 3 weeks for subsequent cycles, and that dose will be used in future trials. Six patients (16%) had partial responses according to computed tomography-based Response Evaluation Criteria in Solid Tumors, and 16 patients (42%) had stabilization as their best response (58% disease control). The median overall survival was 7.7 months for all 38 patients, including 11.8 months for those who received repeated cycles (46% [6 of 13 patients] ≥1 year), with improved efficacy at

  16. Modern trends in radioimmunotherapy of cancer. Pre targeting strategies for the treatment of ovarian cancer

    Energy Technology Data Exchange (ETDEWEB)

    Mcquarrie, S.A.; Xiao, Z.; Mercer, J. R.; Suresh, M. R. [Edmonton Univ. of Alberta, Edmonton, AL (Canada). Faculty of Pharmacy and Pharmaceutical Sciences; Miller, G. G. [University of Alberta, Noujaim Institute for Pharmaceutical Oncology Research, Edmonton, AL (Canada)

    2001-06-01

    A review of published data on some of the problems associated in treating cancer using radioimmunotherapy is presented. Potential improvements for this type of therapy using pretargeting strategies are discussed and preliminary results on a novel multistep regimen to treat human ovarian cancer are presented. A pretargeting strategy using ovarian cancer are presented. A pretargeting strategy using a biotinylated, anti-CA 125 monoclonal antibody (MAb) to attract biotinylated long-circulating liposomes to the surface of CA 125-expressing ovarian cancer cells, was employed. Confocal laser scanning microscopy and fluorescent labels were used to establish the biodistribution patterns in NIH:OVCAR-3 (CA-125 positive) and SK-OV-3 (CA-125 negative) human ovarian cancer cells. Shedding kinetics of the pretargeted stage were measured using {sup 125}I labeled MAbs. No significant internalization of the MAb used in the pretargeting step was observed by 4 hrs. The antibody was gradually internalized starting at 6 hrs, and most of the labelled MAb was detected in cytoplasm by 24 hrs. Shedding and exocytosis of the antigen-MAb complex was not significant for up to 6-hours following administration of the iodinated MAb. Biotinylated liposomes were shown to specifically target the biotinylated MAb/streptavidin complex on the cell surface. It has been demonstrated that by a three-step pretargeting approach, biotinylated liposomes can be specifically delivered to cells pretargeted with biotinylated MAb/SAv complex. The slow internalization and shedding properties of the two MAbs are ideal for multistep pretargeting methods. A successful multistep linkage was established with the biotinylated MAb B27.1, streptavidin and biotinylated liposomes to OVCAR-3 cells, but not to SK-OV-3 cells.

  17. Modern trends in radioimmunotherapy of cancer. Pre targeting strategies for the treatment of ovarian cancer

    International Nuclear Information System (INIS)

    A review of published data on some of the problems associated in treating cancer using radioimmunotherapy is presented. Potential improvements for this type of therapy using pretargeting strategies are discussed and preliminary results on a novel multistep regimen to treat human ovarian cancer are presented. A pretargeting strategy using ovarian cancer are presented. A pretargeting strategy using a biotinylated, anti-CA 125 monoclonal antibody (MAb) to attract biotinylated long-circulating liposomes to the surface of CA 125-expressing ovarian cancer cells, was employed. Confocal laser scanning microscopy and fluorescent labels were used to establish the biodistribution patterns in NIH:OVCAR-3 (CA-125 positive) and SK-OV-3 (CA-125 negative) human ovarian cancer cells. Shedding kinetics of the pretargeted stage were measured using 125I labeled MAbs. No significant internalization of the MAb used in the pretargeting step was observed by 4 hrs. The antibody was gradually internalized starting at 6 hrs, and most of the labelled MAb was detected in cytoplasm by 24 hrs. Shedding and exocytosis of the antigen-MAb complex was not significant for up to 6-hours following administration of the iodinated MAb. Biotinylated liposomes were shown to specifically target the biotinylated MAb/streptavidin complex on the cell surface. It has been demonstrated that by a three-step pretargeting approach, biotinylated liposomes can be specifically delivered to cells pretargeted with biotinylated MAb/SAv complex. The slow internalization and shedding properties of the two MAbs are ideal for multistep pretargeting methods. A successful multistep linkage was established with the biotinylated MAb B27.1, streptavidin and biotinylated liposomes to OVCAR-3 cells, but not to SK-OV-3 cells

  18. PET/CT Imaging and Radioimmunotherapy of Prostate Cancer

    DEFF Research Database (Denmark)

    Bouchelouche, Kirsten; Tagawa, Scott T; Goldsmith, Stanley J;

    2011-01-01

    disease (ideal for antigen access and antibody delivery). Furthermore, prostate cancer is also radiation sensitive. Prostate-specific membrane antigen is expressed by virtually all prostate cancers, and represents an attractive target for RIT. Antiprostate-specific membrane antigen RIT demonstrates...

  19. Dosimetric model for intraperitoneal targeted liposomal radioimmunotherapy of ovarian cancer micrometastases

    Energy Technology Data Exchange (ETDEWEB)

    Syme, A M [Department of Physics, University of Alberta, 412 Avadh Bhatia Physics Laboratory, Edmonton, Alberta T6G 2J1 (Canada); McQuarrie, S A [Faculty of Pharmacy and Pharmaceutical Sciences, University of Alberta, 3118 Dentistry/Pharmacy Centre, Edmonton, Alberta T6G 2N8 (Canada); Middleton, J W [Department of Physics, University of Ottawa, 150 Louis Pasteur, Ottawa, Ontario K1N 6N5 (Canada); Fallone, B G [Departments of Physics and Oncology, University of Alberta, 11560 University Avenue, Edmonton, Alberta T6G 1Z2 (Canada)

    2003-05-21

    A simple model has been developed to investigate the dosimetry of micrometastases in the peritoneal cavity during intraperitoneal targeted liposomal radioimmunotherapy. The model is applied to free-floating tumours with radii between 0.005 cm and 0.1 cm. Tumour dose is assumed to come from two sources: free liposomes in solution in the peritoneal cavity and liposomes bound to the surface of the micrometastases. It is assumed that liposomes do not penetrate beyond the surface of the tumours and that the total amount of surface antigen does not change over the course of treatment. Integrated tumour doses are expressed as a function of biological parameters that describe the rates at which liposomes bind to and unbind from the tumour surface, the rate at which liposomes escape from the peritoneal cavity and the tumour surface antigen density. Integrated doses are translated into time-dependent tumour control probabilities (TCPs). The results of the work are illustrated in the context of a therapy in which liposomes labelled with Re-188 are targeted at ovarian cancer cells that express the surface antigen CA-125. The time required to produce a TCP of 95% is used to investigate the importance of the various parameters. The relative contributions of surface-bound radioactivity and unbound radioactivity are used to assess the conditions required for a targeted approach to provide an improvement over a non-targeted approach during intraperitoneal radiation therapy. Using Re-188 as the radionuclide, the model suggests that, for microscopic tumours, the relative importance of the surface-bound radioactivity increases with tumour size. This is evidenced by the requirement for larger antigen densities on smaller tumours to affect an improvement in the time required to produce a TCP of 95%. This is because for the smallest tumours considered, the unbound radioactivity is often capable of exerting a tumouricidal effect before the targeting agent has time to accumulate

  20. Cuban Monoclonal Antibodies for Radioimmunodiagnosis and Radioimmunotherapy of Cancer Diseases

    International Nuclear Information System (INIS)

    The Centre of Molecular Immunology produces monoclonal antibodies for treating cancer diseases. We are mainly focus on two target systems; one is the epidermal growth factor receptor (EGF-R) because there is a tremendous relationship between the EGF/EGF-R system and several human tumours such as lung, head and neck, ovarian breast and brain cancers; the second one is the ganglioside system, the relevance of certain gangliosides in tumour growth and metastatic dissemination has been well documented, GM3(NeuGc) ganglioside is particularly interesting due to its restrictive expression in normal human tissues. Nimotuzumab (h-R3) is a humanized monoclonal antibody (mAb) that was obtained by complementarity-determining regions grafting of a murine mAb (ior egf/r3) to a human framework having remarkable antiproliferative, pro-apoptotic, and antiangiogenic effects. A Phase I clinical trial was performed to evaluate the toxicity and clinical effect of an intracavitary (intracerebral) administration of a single dose of nimotuzumab (h-R3) labelled with increasing doses of 188Re. All patients bearing astrocytomas grade III/IV should be treated previously with conventional therapies and have an EGF-R overexpression in the tumour, demonstrated by immunohistochemical study. Maximal tolerated dose was 3 mg of the h-R3 labelled with 10 mCi of 188Re. The radioimmunoconjugate showed a high retention in the surgical created resection cavity and the brain adjacent tissues with a mean value of 85.5% of the injected dose one hour post-administration. This radioimmunoconjugate may be relatively safe and a promising therapeutic approach for treating high grade gliomas. GM3(NeuGc) ganglioside is particularly interesting due to its restrictive expression in normal human tissues according to immunohistochemical studies, using either polyclonal or monoclonal antibodies. But both immunohistochemical and biochemical methods have strongly suggested its over-expression in human breast and colon

  1. Radioimmunotherapy: A Specific Treatment Protocol for Cancer by Cytotoxic Radioisotopes Conjugated to Antibodies

    Directory of Open Access Journals (Sweden)

    Hidekazu Kawashima

    2014-01-01

    Full Text Available Radioimmunotherapy (RIT represents a selective internal radiation therapy, that is, the use of radionuclides conjugated to tumor-directed monoclonal antibodies (including those fragments or peptides. In a clinical field, two successful examples of this treatment protocol are currently extended by 90Y-ibritumomab tiuxetan (Zevalin and 131I-tositumomab (Bexxar, both of which are anti-CD20 monoclonal antibodies coupled to cytotoxic radioisotopes and are approved for the treatment of non-Hodgkin lymphoma patients. In addition, some beneficial observations are obtained in preclinical studies targeting solid tumors. To date, in order to reduce the unnecessary exposure and to enhance the therapeutic efficacy, various biological, chemical, and treatment procedural improvements have been investigated in RIT. This review outlines the fundamentals of RIT and current knowledge of the preclinical/clinical trials for cancer treatment.

  2. Aptamer-based radioimmunotherapy. The feasibility and prospect in cancer therapy

    International Nuclear Information System (INIS)

    Radioimmunotherapy (RIT) has emerged as an attractive and promising strategy for the management of malignant diseases. It has been proven to be quite effective in the treatment of numerous tumors, such as non-Hodgkin lymphoma, metastatic prostate cancer, melanoma, thyroid cancer, colon cancer and so on. The RIT currently used is mainly based on monoclonal antibodies to recognize target antigens. As antibodies are large molecules, this method of RIT has some limitations in in vivo use, such as the immunogenicity, the high costs and low efficiency of production. Aptamer is discovered and selected by SELEX technology. As specific recognizers and binders, aptamers and antibodies have such a close similarity as to be interchangeable to some extent. But, aptamers have many advantages over antibodies: higher affinity and specificity, smaller molecular weight, more easily synthesized and modified, more rapidly penetrating into tumors, higher tumor-to-blood distribution ratio and more easily to be cleared. In addition, since aptamer has almost no immunogenicity in vivo, it can be repeatedly administered. Thus, we believe that aptamer-based RIT will be a feasible and promising way to treat human cancers, and it might display better results in cancer treatment than antibody-based RIT. In conclusion, aptamer-based RIT is hopeful to become a key therapeutics in cancer radiotherapy in the near future. (author)

  3. Radiolabeling of trastuzumab with 177Lu via DOTA, a new radiopharmaceutical for radioimmunotherapy of breast cancer

    International Nuclear Information System (INIS)

    Aim: Trastuzumab is a monoclonal antibody that is used in treating breast cancer. We labeled this monoclonal antibody with lutetium-177 and performed in vitro quality control tests as a first step in the production of a new radiopharmaceutical. Material and Methods: Trastuzumab was labeled with lutetium-177 using DOTA as chelator. Radiochemical purity and stability in buffer and human blood serum were determined using thin layer chromatography. Immunoreactivity and toxicity of the complex were tested on MCF7 breast cancer cell line. Results: The radiochemical purity of the complex was 96±0.9%. The stabilities in phosphate buffer and in human blood serum at 96 h postpreparation were 93±1.2% and 85±3.5%, respectively. The immunoreactivity of the complex was 89±1.4%. At a concentration of 1 nM, the complex killed 70±3% of MCF7 cells. At 1.9 nM, 90±5% of the cells were killed. Conclusions: The results showed that the new complex could be considered for further evaluation in animals and possibly in humans as a new radiopharmaceutical for use in radioimmunotherapy against breast cancer.

  4. Alpha-emitting radioisotopes production for radioimmunotherapy

    Energy Technology Data Exchange (ETDEWEB)

    Chun, Kwon Soo [Korea Institutet of Radiological and Medical Sciences, Seoul (Korea, Republic of)

    2007-02-15

    This review discusses the production of alpha-particle-emitting radionuclides in radioimmunotherapy. Radioimmunotherapy labeled with alpha-particle is expected to be very useful for the treatment of monocellular cancer (e.g. leukemia) and micrometastasis at an early stage, residual tumor remained in tissues after chemotherapy and tumor resection, due to the high linear energy transfer (LET) and the short path length in biological tissue of alpha particle. Despite of the expected effectiveness of alpha-particle in radioimmunotherapy, its clinical research has not been activated by the several reasons, shortage of a suitable a-particle development and a reliable radionuclide production and supply system, appropriate antibody and chelator development. Among them, the establishment of radionuclide development and supply system is a key factor to make an alpha-immunotherapy more popular in clinical trial. Alpha-emitter can be produced by several methods, natural radionuclides, reactor irradiation, cyclotron irradiation, generator system and elution. Due to the sharply increasing demand of {sup 213}Bi, which is a most promising radionuclide in radioimmunotherapy and now has been produced with reactor, the cyclotron production system should be developed urgently to meet the demand.

  5. Combined treatment of advanced oropharyngeal cancer with external radiotherapy and three-step radioimmunotherapy

    International Nuclear Information System (INIS)

    The prognosis of patients with locally advanced head and neck cancer remains grim due to poor locoregional tumour control. In the attempt to eradicate residual disease, various novel modalities have been tested, among which radioimmunotherapy (RIT) has shown some potential. We present a case of locally advanced oropharyngeal carcinoma successfully treated with a combination of various treatments including surgery, radio-chemotherapy and three-step RIT, with the avidin-biotin pretargeting system. A partial tumour response was achieved after surgery and radio-chemotherapy; persistent disease was documented at computed tomography (CT), ultrasound (US) and immunoscintigraphy (ISG) 10 weeks after the end of chemo-radiotherapy. The good correlation between the tracer localization in the scintigraphic images and residual mass visualized at CT suggested the application of three-step RIT using systemic administration of yttrium-90 (py) biotin. At present, 17 months after RIT, the patient is alive with no evidence of disease as documented by magnetic resonance imaging (MRI) and US. This is the first case of complete clinical remission of a head and neck carcinoma induced by combined treatment including pretargeted RIT with 90Y-biotin. (orig.)

  6. Beta emitters rhenium-188 and lutetium-177 are equally effective in radioimmunotherapy of HPV-positive experimental cervical cancer.

    Science.gov (United States)

    Phaeton, Rebecca; Jiang, Zewei; Revskaya, Ekaterina; Fisher, Darrell R; Goldberg, Gary L; Dadachova, Ekaterina

    2016-01-01

    Cervical cancer caused by the infection with the human papillomavirus (HPV) remains the fourth leading killer of women worldwide. Therefore, more efficacious treatments are needed. We are developing radioimmunotherapy (RIT) of HPV-positive cervical cancers by targeting E6 and E7 viral oncoproteins expressed by the cancer cells with the radiolabeled monoclonal antibodies (mAbs). To investigate the influence of different radionuclides on the RIT efficacy-we performed RIT of experimental cervical cancer with Rhenium-188 ((188) Re) and Lutetium-177 ((177) Lu)-labeled mAb C1P5 to E6. The biodistribution of (188) Re- and (177) Lu-labeled C1P5 was performed in nude female mice bearing CasKi cervical cancer xenografts and the radiation dosimetry calculations for the tumors and organs were carried out. For RIT the mice were treated with 7.4 MBq of either (188) Re-C1P5 or (177) Lu-C1P5 or left untreated, and observed for their tumor size for 28 days. The levels of (188) Re- and (177) Lu-C1P5 mAbs-induced double-strand breaks in CasKi tumors were compared on days 5 and 10 post treatment by staining with anti-gamma H2AX antibody. The radiation doses to the heart and lungs were similar for both (177) Lu-C1P5 and (188) Re-C1P5. The dose to the liver was five times higher for (177) Lu-C1P5. The doses to the tumor were 259 and 181 cGy for (177) Lu-C1P5 and (188) Re-C1P5, respectively. RIT with either (177) Lu-C1P5 or (188) Re-C1P5 was equally effective in inhibiting tumor growth when each was compared to the untreated controls (P = 0.001). On day 5 there was a pronounced staining for gamma H2AX foci in (177) Lu-C1P5 group only and on day 10 it was observed in both (177) Lu-C1P5 and (188) Re-C1P5 groups. (188) Re- and (177) Lu-labeled mAbs were equally effective in arresting the growth of CasKi cervical tumors. Thus, both of these radionuclides are candidates for the clinical trials of this approach in patients with advanced, recurrent or metastatic cervical cancer. PMID:26625938

  7. Improved response of colon cancer xenografts to radioimmunotherapy with pentoxifylline treatment

    International Nuclear Information System (INIS)

    A methylxanthine, pentoxifylline (PTX), has the potential to improve tumour microcirculation and oxygenation in vivo. We aimed to determine whether this agent would enhance the response of tumours to experimental radioimmunotherapy (RIT). Balb/c nu/nu mice with xenografts of LS180 human colon cancer were treated with 4.63 MBq of 131I-A7 anti-colorectal monoclonal antibody. A dose of 50 mg/kg of PTX was administered i.p. immediately after the 131I-A7 injection and daily thereafter for 7 days. The effect of PTX administration on 131I-A7 targeting in tumours was assessed with biodistribution and radioluminography on day 2. Intratumoural pO2 was measured with microelectrodes. The administration of PTX alone did not suppress tumour growth, but the efficacy of RIT with 131I-A7 was significantly improved by PTX: tumour volumes on day 15, relative to the initial volume, were 16.8±3.60 in the non-treated controls, 13.9±2.17 with PTX, 3.43±0.44 with RIT, and 1.86±0.59 with RIT+PTX (P131I-A7. However, intratumoural pO2 was significantly improved by PTX administration: 16.9±9.75 mmHg in control tumours versus 25.6±11.3 mmHg in PTX-treated tumours (P<0.01). These results indicate that PTX-induced radiosensitisation of tumour cells due to better oxygenation is responsible for the better RIT outcomes, because the net radiation absorbed dose to the tumours did not appear to be changed. (orig.)

  8. Improved radioimmunotherapy of hematologic malignancies

    International Nuclear Information System (INIS)

    This research project proposes to develop novel new approaches of improving the radioimmunodetection and radioimmunotherapy of malignancies by augmenting retention of radioimmunoconjugates by tumor cells. The approaches shown to be effective in these laboratory experiments will subsequently be incorporated into out ongoing clinical trials in patients. Specific project objectives include: to study the rates of endocytosis, intracellular routing, and metabolic degradation of radiolabeled monoclonal antibodies targeting tumor-associated antigens on human leukemia and lymphoma cells; To examine the effects of lysosomotropic amines (e.g. chloroquine, amantadine), carboxylic ionophores (monensin, nigericin), and thioamides (propylthiouracil), on the retention of radiolabeled MoAbs by tumor cells; to examine the impact of newer radioiodination techniques (tyramine cellobiose, paraiodobenzoyl) on the metabolic degradation of radioiodinated antibodies; to compare the endocytosis, intracellular routing, and degradation of radioimmunoconjugates prepared with different radionuclides (131Iodine, 111Indium, 90Yttrium, 99mTechnetium, 186Rhenium); and to examine the utility of radioimmunoconjugates targeting oncogene products for the radioimmunotherapy and radioimmunoscintigraphy of cancer

  9. Improved radioimmunotherapy of hematologic malignancies

    Energy Technology Data Exchange (ETDEWEB)

    Press, O.W.

    1992-03-24

    This research project proposes to develop novel new approaches of improving the radioimmunodetection and radioimmunotherapy of malignancies by augmenting retention of radioimmunoconjugates by tumor cells. The approaches shown to be effective in these laboratory experiments will subsequently be incorporated into out ongoing clinical trials in patients. Specific project objectives include: to study the rates of endocytosis, intracellular routing, and metabolic degradation of radiolabeled monoclonal antibodies targeting tumor-associated antigens on human leukemia and lymphoma cells; To examine the effects of lysosomotropic amines (e.g. chloroquine, amantadine), carboxylic ionophores (monensin, nigericin), and thioamides (propylthiouracil), on the retention of radiolabeled MoAbs by tumor cells; to examine the impact of newer radioiodination techniques (tyramine cellobiose, paraiodobenzoyl) on the metabolic degradation of radioiodinated antibodies; to compare the endocytosis, intracellular routing, and degradation of radioimmunoconjugates prepared with different radionuclides ({sup 131}Iodine, {sup 111}Indium, {sup 90}Yttrium, {sup 99m}Technetium, {sup 186}Rhenium); and to examine the utility of radioimmunoconjugates targeting oncogene products for the radioimmunotherapy and radioimmunoscintigraphy of cancer.

  10. Choice of radionuclides for radioimmunotherapy

    International Nuclear Information System (INIS)

    Innumerable questions need to be answered and obstacles overcome before radioimmunotherapy can be generally successful in cancer patients. Major developments have greatly enhanced the likelihood of success. The important development of appropriate radionuclides and radiochemistry for this therapy must be intimately linked with the biological and biochemical realities. All aspects must be considered, such as the specific nature of the antigenic target, the pharmacokinetics of the antibody fragment carrier, the capability of in vivo quantitation of tumor uptake and turnover time, as well as total body kinetics. With this knowledge, then, practical radiochemistry methods can be integrated with the suitable radionuclide choices, and production methods can be developed which will deliver effective and dependable products for patient therapy

  11. SU-C-201-05: Imaging 212Pb-TCMC-Trastuzumab for Alpha Radioimmunotherapy for Ovarian Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Shen, S; Meredith, R; Azure, M; Yoder, D [University of Alabama, Birmingham, AL (United States); Torgue, J; Banaga, E [AREVA Med LLC, Bethesda, MD (United States)

    2015-06-15

    Purpose: To support the phase I trial for toxicity, biodistribution and pharmacokinetics of intra-peritoneal (IP) 212Pb-TCMC-trastuzumab in patients with HER-2 expressing malignancy. A whole body gamma camera imaging method was developed for estimating amount of 212Pb-TCMC-trastuzumab left in the peritoneal cavity. Methods: {sup 212}Pb decays to {sup 212}Bi via beta emission. {sup 212}Bi emits an alpha particle at an average of 6.1 MeV. The 238.6 keV gamma ray with a 43.6% yield can be exploited for imaging. Initial phantom was made of saline bags with 212Pb. Images were collected for 238.6 keV with a medium energy general purpose collimator. There are other high energy gamma emissions (e.g. 511keV, 8%; 583 keV, 31%) that penetrate the septae of the collimator and contribute scatter into 238.6 keV. An upper scatter window was used for scatter correction for these high energy gammas. Results: A small source containing 212Pb can be easily visualized. Scatter correction on images of a small 212Pb source resulted in a ∼50% reduction in the full width at tenth maximum (FWTM), while change in full width at half maximum (FWHM) was <10%. For photopeak images, substantial scatter around phantom source extended to > 5 cm outside; scatter correction improved image contrast by removing this scatter around the sources. Patient imaging, in the 1st cohort (n=3) showed little redistribution of 212Pb-TCMC-trastuzumab out of the peritoneal cavity. Compared to the early post-treatment images, the 18-hour post-injection images illustrated the shift to more uniform anterior/posterior abdominal distribution and the loss of intensity due to radioactive decay. Conclusion: Use of medium energy collimator, 15% width of 238.6 keV photopeak, and a 7.5% upper scatter window is adequate for quantification of 212Pb radioactivity inside peritoneal cavity for alpha radioimmunotherapy of ovarian cancer. Research Support: AREVA Med, NIH 1UL1RR025777-01.

  12. Using anti-VEGF monoclonal antibody and magnetic nanoparticles as double-targeting vector for the radioimmunotherapy of liver cancer

    International Nuclear Information System (INIS)

    Objective: To study the biodistribution of 131I-anti-VEGF monoclonal antibody (Sc-7269)-- Dextran Magnetic Nanoparticles (DMN) in nude mice bearing human liver cancer where an external magnetic field was focused on, and to evaluate its therapeutic effects and security. Methods: 18 nude mice bearing human liver cancer where an external magnetic field was focused on, were used for the biodistribution study after intratumoral injection (n=9) or intravenous injection (n=9) of 131I-Sc-7269--DMN Another 25 tumor-bearing nude mice were divided into five groups, four groups of them were treated with 7.4 MBq/0.1 ml 131I-Sc-7269-DMN, 131I-Sc-7269, 131I- DMN and 131I by a single intratumoral injection, respectively. And an external magnetic field was bound to the tumor of the nude mice that were rejected 131I-Sc-7269--DMN or 131I-DMN. For control study, the remaining one group was injected with Hanks' balanced salt solution. Tumor Growth Delay (TGD) and tumor inhibition rate were observed as antitumor effect. Peripheral white blood cells counts anti the loss of body weight were tested as an indicator of systemic toxicity. Results: The retention percentages of radioactivity (% injected dose per gram, %ID/g) in tumors after intratumoral injection were 104.06%ID/g, 101.58%ID/g and 100.96%ID/g at 4, 24 and 48 h, respectively, while in the case of intravenous injection, the lower %ID/g values were 85.33%ID/g, 89.67%ID/g and 90.00%ID/g, respectively(P131I-Sc-7269--DMN (13.3±3.3d) was the longest, and tumor inhibition rate (89.0%) was the highest, when compared with other groups. However, systemictoxicity was not significantly increased in 131I-Sc-7269-DMN-treated mice as monitqred by the decrease in peripheral white blood cells counts and the loss of body weight. Conclusions: The radioimmunotherapy of intratumoral injection of 131I-Sc-7269-DMN may be safe and efficient for the treatment of liver cancer. Furthermore, the radioimmunotherapy using DMN as a 'carder system' may be a

  13. Development and evaluation of copper-67 and samarium-153 labeled conjugates for tumor radioimmunotherapy

    Energy Technology Data Exchange (ETDEWEB)

    Srivastava, S.C.; Mausner, L.F.; Mease, R.C.; Meinken, G.E.; Joshi, V.; Kolsky, K.; Sweet, M.; Steplewski, Z.

    1995-02-01

    The potential of utilizing receptor-specific agents such as monoclonal antibodies (MAb), and MAb-derived smaller molecules, as carriers of radionuclides for the selective destruction of tumors has stimulated much research activity. The success of such applications depends on many factors, especially the tumor binding properties of the antibody reagent, the efficiency of labeling and in-vivo stability of the radioconjugate and, on the careful choice of the radionuclide best suited to treat the tumor under consideration. The radiolabeled antibody technique for radioimmunotherapy (RIT), however, has experienced many limitations, and its success has not matched the expectations that were raised more than a decade ago. The problems that have been identified include: (i) degradation of antibody immunoreactivity resulting from chemical manipulations required for labeling; (ii) lack of suitable radioisotopes and methods for stable attachment of the radiolabel; (iii) in-vivo instability of the radioimmunoconjugates; (iv) excessive accumulation of activity in non-target locations; and (v) lack of radioimmunoconjugate accessibility to cells internal to a tumor mass. A careful choice of the radionuclide(s) best suited to treat the tumor under consideration is one of the most important requirements for successful radioimmunotherapy. This study evaluates copper 67 and samarium 153 for tumor radioimmunotherapy.

  14. Improved survival of mice bearing liver metastases of colon cancer cells treated with a combination of radioimmunotherapy and antiangiogenic therapy

    International Nuclear Information System (INIS)

    We attempted to determine whether the combined regimen of radioimmunotherapy (RIT) and antiangiogenic therapy would favorably affect the survival of animals bearing liver metastases of colon cancer cells. Daily antiangiogenic therapy with 2-methoxyestradiol (2-ME), 75 mg/kg, was initiated at 3 days following intrasplenic cell inoculation of LS180 colon cancer cells. RIT with 7 MBq of 131I-A7, an IgG1 anti-colorectal monoclonal antibody, or 131I-HPMS-1, an irrelevant IgG1, was conducted at 7 days. Production of vascular endothelial growth factor (VEGF) by LS180 cells was assessed in vitro. All nontreated mice died by 31 days following cell inoculation (n=5). Monotherapy comprising 2-ME treatment resulted in slightly better survival of mice (n=8) (P131I-A7 RIT displayed a marked therapeutic effect (n=8) (P131I-A7 RIT and antiangiogenic therapy demonstrated a superior therapeutic effect in comparison to monotherapy consisting of either RIT or antiangiogenic therapy (n=10) (P131I-HPMS-1 RIT failed to provide an appreciable benefit (n=5). Treatment with 2-ME decreased VEGF production by LS180 cells in a dose-dependent fashion. In conclusion, a combination regimen comprising RIT and antiangiogenic therapy initiated at the early stage of metastasis would be of great benefit in terms of improvement of the therapeutic efficacy with respect to liver metastases. (orig.)

  15. Radioimmunotherapy with engineered antibody fragments

    International Nuclear Information System (INIS)

    Authors have developed and begun evaluating radiometal-chelated (213Bi) engineered antibody fragments as radioimmunotherapy agents that target the HER2/neu (c-erbB-2) antigen. The diabody format was found to have 40-fold greater affinity for HER2/neu and to be associated with significantly greater tumor localization than is achieved with scFv molecule. It is shown that short-lived isotopes like 213Bi would be most effective when used in conjunction with antibodies that targeted diffuse malignancies (leukemia or lymphoma) or when used for very rapid pretargeted radioimmunotherapy application in which the radioisotope is conjugated to a very small ligand

  16. Current research status of radioimmunotherapy monoclonal antibody drug

    International Nuclear Information System (INIS)

    Radioimmunotherapy (RIT) was one of the most important progresses in the field of cancer therapy over the past 20 years. It has been successfully applied in the treatment of blood system tumors such as NHL. For the utilization of RIT in therapy of solid tumors, however, development of more effective monoclonal antibodies, labeling methods and so on are needed. The current status of radionuclides, monoclonal antibodies and drugs commonly used in the RIT were briefly reviewed. (authors)

  17. Eradication of colon cancer cells before tumour formation in the peritoneal cavity of mice treated with intraperitoneal Re-186 radioimmunotherapy

    International Nuclear Information System (INIS)

    A treatment adjuvant to surgical resection of the primary lesion has been proven to be beneficial in improving the prognosis of patients with high risks of peritoneal dissemination of colon cancer. This study was performed to determine the comparative efficacy of intraperitoneal radioimmunotherapy (RIT) using Re-186 or I-131 labeled murine antibodies in the extermination of cancer cells. A murine anti-colorectal IgG1, A7 monoclonal antibody, was radio-labeled either with I-131 (by the chloramine-T method) or Re-186 (by the MAG3 pre-chelated method). A total number of 16 mice were subjected to RIT with Re-186 A7 (N=8) or I-131 A7 (N=8) at equitoxic doses in Balb/c bu/nu mice 10 min after intraperitoneal injection of LS180 human colon cancer cells. A third group of mice were subjected to chemotherapy with 5-fluorouracil at 30 mg/kg for 4 consecutive days following the intraperitoneal injection of the same LS180 human colon cancer cells. There were 19 mice in the control group who were not subjected to any form of therapy. The results revealed that the mean survival of mice in the control (N-19), I-131 A7 RIT (N=8) and Chemotherapy (N=6) groups were 33.8 ± 1.0, 80.1 ± 2.5 and 49.3 ± 5.3 days respectively. The eight mice who were subjected to Re-186 A7 RIT showed much better survival compared to the other groups. Two of the eight mice from this group died at 105 and 111 days following Re-186 A7 RIT. Other six mice were sacrificed at 172 days, and autopsy revealed no macroscopic peritoneal tumor growth. Based on this pilot study we concluded that individual tumor cells in the peritoneal cavity would be effectively exterminated by intraperitoneal RIT with Re-186 A7. (author)

  18. Radioimmunotherapy of the lymphoma; Radioimmunotherapie du lymphome

    Energy Technology Data Exchange (ETDEWEB)

    Bodet-Milin, C.; Kraeber-Bodere, F. [Hotel Dieu, Service de Medecine Nucleaire, 44 - Nantes (France); Kraeber-Bodere, F. [Centre Regional de Lutte Contre le Cancer Rene-Gauducheau, Service de Medecine Nucleaire, 44 - Nantes (France)

    2006-09-15

    The radioimmunotherapy is a kind of internal radiotherapy using as vectorization agent a monoclonal antibody, recognizing an antigen expressed by tumor cells, coupled to a radioisotope. Developed now from more than twenty years, its efficiency is demonstrated in hematology for the treatment of the B lymphomas. The murine monoclonal antibody ( anti -CD20) and labelled with Yttrium 90 can be used in clinical routine in the treatment of recurrences of L.N.H. of low grade CD20 positive among the adults resistant or relapsing after treatment by rituximab, leading to response rate about 70 to 80 % with 20 to 30 % of complete response. The benefits of the R.I.T. will be probably more significant in first therapy line, in strengthening after a treatment by chemo- immunotherapy or in the frame of myelo ablative protocols. (N.C.)

  19. Radioimmunotherapy with 90Y-labeled monoclonal antibodies in a nude mouse ovarian cancer model

    International Nuclear Information System (INIS)

    Tumor stroma contains much fibrin, and so monoclonal antifibrin antibody can accumulate in tumors. We treated nude mice bearing human ovarian carcinoma xenografts with 90Y-labeled monoclonal antifibrin antibody Fab fragments administered intratumorally. The survival time vs. a control group was significantly prolonged and tumor growth rate was decreased. Another group of animals was treated with 90Y-labeled OC 125-monoclonal antibody; these mice received the antibodies intratumorally, intraperitoneally or intravenously. The survival time was longest in the intratumorally treated group. There was no significant difference in survival between 90Y-labeled OC 125 and antifibrin in the intratumorally treated animal groups. The tissue activity distribution studies revealed that bone marrow is the critical organ. Intratumorally injected monoclonal 90Y-antifibrin antibodies were retained at least 36 h (up to 50% of injected activity per gram tumor tissue) in the xenograft after one treatment, causing cell death. Beta-camera imaging and immunohistochemistry were performed for studies of the correlation between 90Y activity and fibrin distribution in tumor specimens. These results were in concordance. In conclusion, intratumoral administration seems suitable for radioimmunotherapy, with an antibody that targets stromal structures. The accumulation can be successfully monitored by a beta-camera. (orig.)

  20. Three-step radioimmunotherapy with yttrium-90 biotin: dosimetry and pharmacokinetics in cancer patients

    International Nuclear Information System (INIS)

    A three-step avidin-biotin approach has been applied as a pretargeting system in radioimmunotherapy (RIT) as an alternative to conventional RIT with directly labelled monoclonal antibodies (MoAbs). Although dosimetric and toxicity studies following conventional RIT have been reported, these aspects have not previously been evaluated in a three-step RIT protocol. This report presents the results of pharmacokinetic and dosimetric studies performed in 24 patients with different tumours. Special consideration was given to the dose delivered to the red marrow and to the haematological toxicity. The possible additive dose to red marrow due to the release of unbound yttrium-90 was investigated. The protocol consisted in the injection of biotinylated MoAbs (first step) followed 1 day later by the combined administration of avidin and streptavidin (second step). After 24 h, biotin radiolabelled with 1.85-2.97 GBq/m2 of 90Y was injected (third step). Two different chelating agents, DTPA and DOTA, coupled to biotin, were used in these studies. Indium-111 biotin was used as a tracer of 90Y to follow the biodistribution during therapy. Serial blood samples and complete urine collection were obtained over 3 days. Whole-body and single-photon emission tomography images were acquired at 1, 16, 24 and 40 h after injection. The sequence of images was used to extrapolate 90Y-biotin time-activity curves. Numerical fitting and compartmental modelling were used to calculate the residence time values (τ) for critical organs and tumour, and results were compared; the absorbed doses were estimated using the MIRDOSE3.1 software. The residence times obtained by the numerical and compartmental models showed no relevant differences (90Y activities capable of delivering a high dose to the tumour and sparing red marrow and other normal organs. Although 90Y-biotin clears rapidly from circulation, the use of DOTA-biotin conjugate for a stable chelation of 90Y is strongly recommended, considering

  1. Chemo radioimmunotherapy with 5-fluorouracil, cisplatin and interferon-α in pancreatic and peri-ampullary cancer: Results of a feasibility study

    International Nuclear Information System (INIS)

    Background: Recent studies give rise to the hypothesis, that adjuvant chemo radioimmunotherapy with 5-fluorouracil (5-F.U.), cisplatin and interferon-a (I.F.N.-a) might be a possible new treatment of pancreatic cancer in resected patients. We report the up-to-now experience at our institution. Patients and methods: Eleven patients with histological diagnosis of localized carcinoma of the pancreas (n = 7) or peri-ampullary (n = 4) were prospectively analyzed. Four patients were deemed unresectable because of local invasion of adjacent organs (neo-adjuvant setting) and seven patients underwent curative resection (adjuvant setting). Eight patients were classified as T3 carcinomas and three T4 carcinomas. Fifty-five per cent (6/11) of the patients presented with positive lymph node involvement. One histological Grade I, six Grade II and three Grade III were detected. External conformal irradiation to a total dose of 50.4 Gy with 1.8 Gy per day was delivered. All patients received a concomitant chemotherapy with continuous 5-F.U. 200 mg/m2 per day on 28 treatment days and intravenous bolus cisplatin 30 mg/m2 per week (Day 2, 9, 16, 23, 30). A recombinant r-I.F.N.-a was administered on three days weekly during Week one to five of the radiotherapy course as subcutaneous injections with 3*3 Mio. I.U. weekly. Results: The four-year overall survival rate for all patients was 55%. In the neo-adjuvant group, three of four patients died due to progressive disease; in the adjuvant group, combined chemo radioimmunotherapy lead to controlled disease in five of seven patients. The overall toxicity was well-managed. Conclusion: Our data strengthens the hypothesis of concomitant chemo radioimmunotherapy with 5-F.U., I.F.N.-a and cisplatin as a possible new treatment of pancreatic cancer in resected patients. (authors)

  2. Improved radioimmunotherapy of hematologic malignancies. [Final report

    Energy Technology Data Exchange (ETDEWEB)

    Press, O.W.

    1992-03-24

    This research project proposes to develop novel new approaches of improving the radioimmunodetection and radioimmunotherapy of malignancies by augmenting retention of radioimmunoconjugates by tumor cells. The approaches shown to be effective in these laboratory experiments will subsequently be incorporated into out ongoing clinical trials in patients. Specific project objectives include: to study the rates of endocytosis, intracellular routing, and metabolic degradation of radiolabeled monoclonal antibodies targeting tumor-associated antigens on human leukemia and lymphoma cells; To examine the effects of lysosomotropic amines (e.g. chloroquine, amantadine), carboxylic ionophores (monensin, nigericin), and thioamides (propylthiouracil), on the retention of radiolabeled MoAbs by tumor cells; to examine the impact of newer radioiodination techniques (tyramine cellobiose, paraiodobenzoyl) on the metabolic degradation of radioiodinated antibodies; to compare the endocytosis, intracellular routing, and degradation of radioimmunoconjugates prepared with different radionuclides ({sup 131}Iodine, {sup 111}Indium, {sup 90}Yttrium, {sup 99m}Technetium, {sup 186}Rhenium); and to examine the utility of radioimmunoconjugates targeting oncogene products for the radioimmunotherapy and radioimmunoscintigraphy of cancer.

  3. Predictive patient-specific dosimetry and individualized dosing of pretargeted radioimmunotherapy in patients with advanced colorectal cancer

    Energy Technology Data Exchange (ETDEWEB)

    Schoffelen, Rafke; Woliner-van der Weg, Wietske; Visser, Eric P.; Oyen, Wim J.G.; Boerman, Otto C. [Radboud University Medical Center, Department of Radiology and Nuclear Medicine, PO Box 9101, Nijmegen (Netherlands); Goldenberg, David M. [Garden State Cancer Center, Morris Plains, NJ (United States); Immunomedics, Inc., Morris Plains, NJ (United States); IBC Pharmaceuticals, Inc., Morris Plains, NJ (United States); Sharkey, Robert M.; McBride, William J.; Chang, Chien-Hsing [Immunomedics, Inc., Morris Plains, NJ (United States); Rossi, Edmund A. [IBC Pharmaceuticals, Inc., Morris Plains, NJ (United States); Graaf, Winette T.A. van der [Radboud University Medical Center, Department of Medical Oncology, Nijmegen (Netherlands)

    2014-08-15

    Pretargeted radioimmunotherapy (PRIT) with bispecific antibodies (bsMAb) and a radiolabeled peptide reduces the radiation dose to normal tissues. Here we report the accuracy of an {sup 111}In-labeled pretherapy test dose for personalized dosing of {sup 177}Lu-labeled IMP288 following pretargeting with the anti-CEA x anti-hapten bsMAb, TF2, in patients with metastatic colorectal cancer (CRC). In 20 patients bone marrow absorbed doses (BMD) and doses to the kidneys were predicted based on blood samples and scintigrams acquired after {sup 111}In-IMP288 injection for individualized dosing of PRIT with {sup 177}Lu-IMP288. Different dose schedules were studied, varying the interval between the bsMAb and peptide administration (5 days vs. 1 day), increasing the bsMAb dose (75 mg vs. 150 mg), and lowering the peptide dose (100 μg vs. 25 μg). TF2 and {sup 111}In/{sup 177}Lu-IMP288 clearance was highly variable. A strong correlation was observed between peptide residence times and individual TF2 blood concentrations at the time of peptide injection (Spearman's ρ = 0.94, P < 0.0001). PRIT with 7.4 GBq {sup 177}Lu-IMP288 resulted in low radiation doses to normal tissues (BMD <0.5 Gy, kidney dose <3 Gy). Predicted {sup 177}Lu-IMP288 BMD were in good agreement with the actual measured doses (mean ± SD difference -0.0026 ± 0.028 mGy/MBq). Hematological toxicity was mild in most patients, with only two (10 %) having grade 3-4 thrombocytopenia. A correlation was found between platelet toxicity and BMD (Spearman's ρ = 0.58, P = 0.008). No nonhematological toxicity was observed. These results show that individual high activity doses in PRIT in patients with CEA-expressing CRC could be safely administered by predicting the radiation dose to red marrow and kidneys, based on dosimetric analysis of a test dose of TF2 and {sup 111}In-IMP288. (orig.)

  4. Pharmacokinetics and Dosimetry Studies for Optimization of Pretargeted Radioimmunotherapy in CEA-Expressing Advanced Lung Cancer Patients

    Directory of Open Access Journals (Sweden)

    Caroline eBodet-Milin

    2015-11-01

    Full Text Available Objectives. A phase I pretargeted radioimmunotherapy trial (EudractCT 200800603096 was designed in patients with metastatic lung cancer expressing carcinoembryonic antigen (CEA to optimize bispecific antibody and labelled peptide doses, as well as the delay between their injections.Methods. Three cohorts of 3 patients received the anti-CEA x anti-histamine-succinyl-glycine (HSG humanized trivalent bispecific antibody (TF2 and the IMP288 bivalent HSG-peptide. Patients underwent a pre-therapeutic imaging session S1 (44 or 88 nmol/m2 of TF2 followed by 4.4 nmol/m2, 185 MBq, of 111In-labelled IMP288, and, 1-2 weeks later, a therapy session S2 (240 or 480 nmol/m2 of TF2 followed by 24 nmol/m2, 1.1 GBq/m2, 177Lu-labeled IMP288. The pretargeting delay was 24 or 48 hours. The dose schedule was defined based on pre-clinical TF2 pharmacokinetic studies, on our previous clinical data using the previous anti-CEA pretargeting system and on clinical results observed in the first patients injected using the same system in the Netherlands.Results. TF2 pharmacokinetics (PK was represented by a two-compartment model in which the central compartment volume was linearly dependent on the patient's surface area. PK were remarkably similar, with a clearance of 0.33 +/- 0.03 L/h per m2. 111In- and 177Lu-IMP288 PK were also well represented by a two-compartment model. IMP288 PK were faster (clearance 1.4 to 3.3 l/h. The central compartment volume was proportional to body surface area and IMP288clearance depended on the molar ratio of injected IMP288 to circulating TF2 at the time of IMP288 injection. Modelling of image quantification confirmed the dependence of IMP288 kinetics on circulating TF2, but tumour activity PK were variable. Organ absorbed doses were not significantly different in the 3 cohorts, but the tumour dose was significantly higher with the higher molar doses of TF2 (p < 0.002. S1 imaging predicted absorbed doses calculated in S2. Conclusion. The best

  5. Non-invasive visualisation of the development of peritoneal carcinomatosis and tumour regression after 213Bi-radioimmunotherapy using bioluminescence imaging

    International Nuclear Information System (INIS)

    Non-invasive imaging of tumour development remains a challenge, especially for tumours in the intraperitoneal cavity. Therefore, the aim of this study was the visualisation of both the development of peritoneal carcinomatosis and tumour regression after radioimmunotherapy with tumour-specific 213Bi-Immunoconjugates, via in vivo bioluminescence imaging of firefly luciferase-transfected cells. Human diffuse-type gastric cancer cells expressing mutant d9-E-cadherin were stably transfected with firefly luciferase (HSC45-M2-luc). For bioluminescence imaging, nude mice were inoculated intraperitoneally with 1 x 107 HSC45-M2-luc cells. On days 4 and 8 after tumour cell inoculation, imaging was performed following D-luciferin injection using a cooled CCD camera with an image intensifier unit. For therapy, mice were injected with 2.7 MBq 213Bi-d9MAb targeting d9-E-cadherin on day 8 after tumour cell inoculation. Bioluminescence images were taken every 4 days to monitor tumour development. After i.p. inoculation of HSC45-M2-luc cells into nude mice, development as well as localisation of peritoneal carcinomatosis could be visualised using bioluminescence imaging. Following 213Bi-d9MAb therapy on day 8 after intraperitoneal inoculation of HSC45-M2-luc cells, small tumour nodules were totally eliminated and larger nodules showed a clear reduction in size on day 12 after tumour cell inoculation. Subsequently a recurrence of tumour mass was observed, starting from the remaining tumour spots. By measuring the mean grey level intensity, tumour development over time could be demonstrated. Non-invasive bioluminescence imaging permits visualisation of the development of peritoneal carcinomatosis, localisation of tumour in the intraperitoneal cavity and evaluation of therapeutic success after 213Bi-d9MAb treatment. (orig.)

  6. Fully human IgG and IgM antibodies directed against the carcinoembryonic antigen (CEA) Gold 4 epitope and designed for radioimmunotherapy (RIT) of colorectal cancers

    International Nuclear Information System (INIS)

    Human monoclonal antibodies (MAbs) are needed for colon cancer radioimmunotherapy (RIT) to allow for repeated injections. Carcinoembryonic antigen (CEA) being the reference antigen for immunotargeting of these tumors, we developed human anti-CEA MAbs. XenoMouse®-G2 animals were immunized with CEA. Among all the antibodies produced, two of them, VG-IgG2κ and VG-IgM, were selected for characterization in vitro in comparison with the human-mouse chimeric anti-CEA MAb X4 using flow cytometry, surface plasmon resonance, and binding to radiolabeled soluble CEA and in vivo in human colon carcinoma LS174T bearing nude mice. Flow cytometry analysis demonstrated binding of MAbs on CEA-expressing cells without any binding on NCA-expressing human granulocytes. In a competitive binding assay using five reference MAbs, directed against the five Gold CEA epitopes, VG-IgG2κ and VG-IgM were shown to be directed against the Gold 4 epitope. The affinities of purified VG-IgG2κ and VG-IgM were determined to be 0.19 ± 0.06 × 108 M-1 and 1.30 ± 0.06 × 108 M-1, respectively, as compared with 0.61 ± 0.05 × 108 M-1 for the reference MAb X4. In a soluble phase assay, the binding capacities of VG-IgG2κ and VG-IgM to soluble CEA were clearly lower than that of the control chimeric MAb X4. A human MAb concentration of about 10-7 M was needed to precipitate approximatively 1 ng 125I-rhCEA as compared with 10-9 M for MAb X4, suggesting a preferential binding of the human MAbs to solid phase CEA. In vivo, 24 h post-injection, 125I-VG-IgG2κ demonstrated a high tumor uptake (25.4 ± 7.3%ID/g), close to that of 131I-X4 (21.7 ± 7.2%ID/g). At 72 h post-injection, 125I-VG-IgG2κ was still concentrated in the tumor (28.4 ± 11.0%ID/g) whereas the tumor concentration of 131I-X4 was significantly reduced (12.5 ± 4.8%ID/g). At no time after injection was there any accumulation of the radiolabeled MAbs in normal tissues. A pertinent analysis of VG-IgM biodistribution was not possible in this

  7. Fully human IgG and IgM antibodies directed against the carcinoembryonic antigen (CEA Gold 4 epitope and designed for radioimmunotherapy (RIT of colorectal cancers

    Directory of Open Access Journals (Sweden)

    Pugnière Martine

    2004-10-01

    Full Text Available Abstract Background Human monoclonal antibodies (MAbs are needed for colon cancer radioimmunotherapy (RIT to allow for repeated injections. Carcinoembryonic antigen (CEA being the reference antigen for immunotargeting of these tumors, we developed human anti-CEA MAbs. Methods XenoMouse®-G2 animals were immunized with CEA. Among all the antibodies produced, two of them, VG-IgG2κ and VG-IgM, were selected for characterization in vitro in comparison with the human-mouse chimeric anti-CEA MAb X4 using flow cytometry, surface plasmon resonance, and binding to radiolabeled soluble CEA and in vivo in human colon carcinoma LS174T bearing nude mice. Results Flow cytometry analysis demonstrated binding of MAbs on CEA-expressing cells without any binding on NCA-expressing human granulocytes. In a competitive binding assay using five reference MAbs, directed against the five Gold CEA epitopes, VG-IgG2κ and VG-IgM were shown to be directed against the Gold 4 epitope. The affinities of purified VG-IgG2κ and VG-IgM were determined to be 0.19 ± 0.06 × 108 M-1 and 1.30 ± 0.06 × 108 M-1, respectively, as compared with 0.61 ± 0.05 × 108 M-1 for the reference MAb X4. In a soluble phase assay, the binding capacities of VG-IgG2κ and VG-IgM to soluble CEA were clearly lower than that of the control chimeric MAb X4. A human MAb concentration of about 10-7 M was needed to precipitate approximatively 1 ng 125I-rhCEA as compared with 10-9 M for MAb X4, suggesting a preferential binding of the human MAbs to solid phase CEA. In vivo, 24 h post-injection, 125I-VG-IgG2κ demonstrated a high tumor uptake (25.4 ± 7.3%ID/g, close to that of 131I-X4 (21.7 ± 7.2%ID/g. At 72 h post-injection, 125I-VG-IgG2κ was still concentrated in the tumor (28.4 ± 11.0%ID/g whereas the tumor concentration of 131I-X4 was significantly reduced (12.5 ± 4.8%ID/g. At no time after injection was there any accumulation of the radiolabeled MAbs in normal tissues. A pertinent analysis of

  8. Positron emission tomography/computed tomography and radioimmunotherapy of prostate cancer

    DEFF Research Database (Denmark)

    Bouchelouche, Kirsten; Capala, Jacek; Oehr, Peter

    2009-01-01

    available. This review highlights the most important achievements within the last year in PET/CT and RIT of prostate cancer. RECENT FINDINGS: Conflicting results exist on the use of choline for detection of malignant disease in the prostate gland. The role of PET/CT in N-staging remains to be elucidated...... further. However, F-choline and C-choline PET/CT have been demonstrated to be useful for detection of recurrence. F-choline and F-fluoride PET/CT are useful for detection of bone metastases. Prostate tumor antigens may be used as targets for RIT. Prostate-specific membrane antigen is currently under focus...... of a number of diagnostic and therapeutic strategies. J591, a monoclonal antibody, which targets the extracellular domain of prostate-specific membrane antigen, shows promising results. HER2 receptors may also have a potential as target for PET/CT imaging and RIT of advanced prostate cancer. SUMMARY...

  9. Effective chelators for 90Y and 212Bi radioimmunotherapy of cancer

    International Nuclear Information System (INIS)

    Advances in synthesis and evaluation of monoclonal antibody (mAb)-ligand bioconjugates are required to further use of 90Y, 212Bi labeled mAb in cancer therapy. The authors have used ligand 1B4M-DTPA for preparation of 90Y-mAb-anti-TAC for an ongoing clinical trial of treatment of adult T-cell leukemia. Good results have been obtained in that of 10 evaluable patients, two are in complete remission 1 yr after initiation of therapy and six experienced partial remissions. Radiochemical dose was limited by marrow suppression, leading the authors to suspect that some 90Y was reaching bone. For this reason, they have prepared ultra-pure 88Y and thereafter 88Y-mAb conjugates with bifunctional DOTA and CHX-DTPA ligands which they have measured to be thermodynamically stronger for yttrium than the 1B4M ligand. The CHX ligand has also been useful for 212Bi-leukemia therapy in mice

  10. Intratumoral radioimmunotherapy of a human colon cancer xenograft using a sustained-release gel

    International Nuclear Information System (INIS)

    Low tumor uptake and normal tissue toxicity limit the efficacy of RIT for the treatment of solid tumors. In this study, an intratumoral injectable gel drug delivery system for local administration of RIT was evaluated using the LS174T human colon cancer xenograft model in SCID mice. The injectable gel is a collagen-based drug delivery system designed for intratumoral (i.t.) administration, which has previously been shown to enhance drug retention at the injection site and reduce systemic drug exposure. We compared the local (tumor) retention and biodistribution of 111In-labeled NR-LU-10 monoclonal antibody given i.t. in the injectable gel versus simple aqueous solution. 111In gel given i.t. and 111In-NR-LU-10 given intraperitoneally (i.p.) were used as controls. The results showed that tumors treated with 111In-NR-LU-10 gel maintained the highest levels of radioactivity for up to 96 h. At 48 h after the administration of 111In-NR-LU-10 gel i.t., 111In-NR-LU-10 solution i.t., 111In gel i.t., or111 In-NR-LU-10 i.p., the level of radioactivity remaining in each gram of tumor was 98, 49, 45, and 16% of the injected dose, respectively. It was estimated that if 100 μCi of 90Y-NR-LU-10 were administered similarly, tumor treated with 90Y-NR-LU-10 gel i.t. would receive a dose of 90.0 Gy, whereas normal tissues in the same animal would receive a dose of approximately 2.43 Gy. In contrast, if 90Y-NR-LU-10 were delivered i.p., a comparable tumor would receive a dose of 16.8 Gy and corresponding normal tissues would receive 3.36 Gy. Consistent with these estimates, enhanced antitumor efficacy was observed when 90Y-NR-LU-10 gel was administered i.t. Tumor growth delay time was 6.9-fold (P 90Y-NR-LU-10 i.p. (2.1 days). Systemic toxicity was also significantly reduced in gel-treated animals as monitored by loss of body weight. This study demonstrated that intratumoral delivery of 90Y-NR-LU-10 gel markedly increased the retention of the radioisotope in tumors, enhanced the

  11. Evaluation of Efficacy of Radioimmunotherapy with 90Y-Labeled Fully Human Anti-Transferrin Receptor Monoclonal Antibody in Pancreatic Cancer Mouse Models.

    Directory of Open Access Journals (Sweden)

    Aya Sugyo

    Full Text Available Pancreatic cancer is an aggressive tumor and the prognosis remains poor. Therefore, development of more effective therapy is needed. We previously reported that 89Zr-labeled TSP-A01, an antibody against transferrin receptor (TfR, is highly accumulated in a pancreatic cancer xenograft, but not in major normal organs. In the present study, we evaluated the efficacy of radioimmunotherapy (RIT with 90Y-TSP-A01 in pancreatic cancer mouse models.TfR expression in pancreatic cancer cell lines (AsPC-1, BxPC-3, MIAPaCa-2 was evaluated by immunofluorescence staining. 111In-labeled anti-TfR antibodies (TSP-A01, TSP-A02 were evaluated in vitro by cell binding assay with the three cell lines and by competitive inhibition assay with MIAPaCa-2. In vivo biodistribution was evaluated in mice bearing BxPC-3 and MIAPaCa-2 xenografts. Tumor volumes of BxPC-3 and MIAPaCa-2 were sequentially measured after 90Y-TSP-A01 injection and histological analysis of tumors was conducted.MIAPaCa-2 cells showed the highest TfR expression, followed by AsPC-1 and BxPC-3 cells. 111In-TSP-A01 and 111In-TSP-A02 bound specifically to the three cell lines according to TfR expression. The dissociation constants for TSP-A01, DOTA-TSP-A01, TSP-A02, and DOTA-TSP-A02 were 0.22, 0.28, 0.17, and 0.22 nM, respectively. 111In-TSP-A01 was highly accumulated in tumors, especially in MIAPaCa-2, but this was not true of 111In-TSP-A02. The absorbed dose for 90Y-TSP-A01 was estimated to be 8.3 Gy/MBq to BxPC-3 and 12.4 Gy/MBq to MIAPaCa-2. MIAPaCa-2 tumors treated with 3.7 MBq of 90Y-TSP-A01 had almost completely disappeared around 3 weeks after injection and regrowth was not observed. Growth of BxPC-3 tumors was inhibited by 3.7 MBq of 90Y-TSP-A01, but the tumor size was not reduced.90Y-TSP-A01 treatment achieved an almost complete response in MIAPaCa-2 tumors, whereas it merely inhibited the growth of BxPC-3 tumors. 90Y-TSP-A01 is a promising RIT agent for pancreatic cancer, although further

  12. Radio-immunotherapy

    International Nuclear Information System (INIS)

    Radioimmunotherapy (R.I.T.) is a new modality of targeted therapy in which irradiation from radionuclides is delivered to tumor targets using monoclonal antibodies (MAb) directed to tumor-associated antigen. R.I.T. has been developed for more than 20 years. Today, R.I.T. can be used in clinical practice using non-ablative activity of murine anti-CD20 90Y-ibritumomab tiuxetan (Zevalin) for treatment of patients with relapsed or refractory follicular lymphomas (F.L.), with overall response rate of 70 to 80% and 20 to 30% of complete response. Different approaches are explored to improve efficacy of R.I.T. in N.H.L.: myelo-ablative R.I.T. or HD treatment, R.I.T. as consolidation after chemotherapy to target M.R.D., R.I.T. in first-line treatment, fractionated R.I.T., R.I.T. using other Ag targets. For solid tumors, interesting results have been obtained using anti-CEA R.I.T. delivered as consolidation treatment or using pre-targeting system. (authors)

  13. Radioimmunotherapy of malignant gliomas

    International Nuclear Information System (INIS)

    Despite all technical advances (intraoperative resection control, fluorescence guided resection, advances in external beam radiation techniques) and new consolidated findings on systemic chemotherapy treatment of malignant gliomas with conventional therapeutic modalities (surgery, radiation therapy and chemotherapy) is still highly unfavourable. Total tumor erradication is impossible due to tumor infiltrations into the normal brain and the limitations given by the limited tolerance of surrounding brain tissue. New treatment strategies, therefore, aim for a more selective destruction of tumor cells. Malignant glioma cells selectively express several antigens or receptors which are not or only to a minor extent present in normal brain tissue. Administration of radiolabelled monoclonal antibodies, especially when given locoregionally, targeting these tumor-specific antigens offers an innovative therapeutic strategy that has recently demonstrated encouraging antitumor effects and acceptable toxicity in many phase I/II clinical trials. This review offers a comprehensive summary of own experiences and results of clinical trials reported in the literature dealing with radioimmunotherapy of malignant glioma and highlights future plans to further develop this therapeutic strategy. (orig.)

  14. Pretargeted radioimmunotherapy of colorectal cancer metastases: models and pharmacokinetics predict influence of the physical and radiochemical properties of the radionuclide

    Energy Technology Data Exchange (ETDEWEB)

    Frampas, Eric; Maurel, Catherine; Remaud-Le Saec, Patricia; Mauxion, Thibault; Faivre-Chauvet, Alain; Davodeau, Francois; Bardies, Manuel; Barbet, Jacques [Universite de Nantes, Inserm, UMR 892, Centre de Recherche en Cancerologie Nantes-Angers (CRCNA), Nantes (France); Goldenberg, David M. [Immunomedics, Inc., Morris Plains, NJ (United States); Center for Molecular Medicine and Immunology, Garden State Cancer Center, Morris Plains, NJ (United States)

    2011-12-15

    We investigated influences of pretargeting variables, tumor location, and radionuclides in pretargeted radioimmunotherapy (PRIT) as well as estimated tumor absorbed doses. LS-174T human colonic carcinoma cells expressing carcinoembryonic antigen (CEA) were inoculated in nude mice. Biodistribution of a bispecific anti-CEA x anti-hapten antibody, TF2, and of a TF2-pretargeted peptide was assessed and a multi-compartment pharmacokinetic model was devised. Tissue absorbed doses were calculated for {sup 131}I, {sup 177}Lu, {sup 90}Y, {sup 211}At, and {sup 213}Bi using realistic specific activities. Under conditions optimized for tumor imaging (10:1 TF2 to peptide molar ratio, interval time 15-24 h), tumor uptake reached {proportional_to}9 ID/g in subcutaneous tumors at 2 h with very low accretion in normal tissues (tumor to blood ratio >20:1 after 2 h). For a low dose of peptide (0.04 nmol), {sup 211}At is predicted to deliver a high absorbed dose to tumors [41.5 Gy considering a relative biologic effect (RBE) of 5], kidneys being dose-limiting. {sup 90}Y and {sup 213}Bi would also deliver high absorbed doses to tumor (18.6 for {sup 90}Y and 26.5 Gy for {sup 213}Bi, taking RBE into account, for 0.1 nmol) and acceptable absorbed doses to kidneys. With hepatic metastases, a twofold higher tumor absorbed dose is expected. Owing to the low activities measured in blood, the bone marrow absorbed dose is expected to be without significant toxicity. Pretargeting achieves high tumor uptake and higher tumor to background ratios compared to direct RIT. Short-lived radionuclides are predicted to deliver high tumor absorbed doses especially {sup 211}At, with kidneys being the dose-limiting organ. {sup 177}Lu and {sup 131}I should be considered for repeated injections. (orig.)

  15. Anti-L1CAM radioimmunotherapy is more effective with the radiolanthanide terbium-161 compared to lutetium-177 in an ovarian cancer model

    Energy Technology Data Exchange (ETDEWEB)

    Gruenberg, Juergen; Lindenblatt, Dennis; Cohrs, Susan; Fischer, Eliane [Paul Scherrer Institute, Center for Radiopharmaceutical Sciences ETH-PSI-USZ, Villigen (Switzerland); Dorrer, Holger [Paul Scherrer Institute, Laboratory of Radiochemistry and Environmental Chemistry, Villigen (Switzerland); Zhernosekov, Konstantin [ITG Isotope Technologies Garching GmbH, Garching (Germany); Koester, Ulli [Institut Laue-Langevin, Grenoble (France); Tuerler, Andreas [Paul Scherrer Institute, Laboratory of Radiochemistry and Environmental Chemistry, Villigen (Switzerland); University of Bern, Department of Chemistry and Biochemistry, Berne (Switzerland); Schibli, Roger [Paul Scherrer Institute, Center for Radiopharmaceutical Sciences ETH-PSI-USZ, Villigen (Switzerland); ETH Zurich, Department of Chemistry and Applied Biosciences, Zurich (Switzerland)

    2014-10-15

    The L1 cell adhesion molecule (L1CAM) is considered a valuable target for therapeutic intervention in different types of cancer. Recent studies have shown that anti-L1CAM radioimmunotherapy (RIT) with {sup 67}Cu- and {sup 177}Lu-labelled internalising monoclonal antibody (mAb) chCE7 was effective in the treatment of human ovarian cancer xenografts. In this study, we directly compared the therapeutic efficacy of anti-L1CAM RIT against human ovarian cancer under equitoxic conditions with the radiolanthanide {sup 177}Lu and the potential alternative {sup 161}Tb in an ovarian cancer therapy model. Tb was produced by neutron bombardment of enriched {sup 160}Gd targets. {sup 161}Tb and {sup 177}Lu were used for radiolabelling of DOTA-conjugated antibodies. The in vivo behaviour of the radioimmunoconjugates (RICs) was assessed in IGROV1 tumour-bearing nude mice using biodistribution experiments and SPECT/CT imaging. After ascertaining the maximal tolerated doses (MTD) the therapeutic impact of 50 % MTD of {sup 177}Lu- and {sup 161}Tb-DOTA-chCE7 was evaluated in groups of ten mice by monitoring the tumour size of subcutaneous IGROV1 tumours. The average number of DOTA ligands per antibody was 2.5 and maximum specific activities of 600 MBq/mg were achieved under identical radiolabelling conditions. RICs were stable in human plasma for at least 48 h. {sup 177}Lu- and {sup 161}Tb-DOTA-chCE7 showed high tumour uptake (37.8-39.0 %IA/g, 144 h p.i.) with low levels in off-target organs. SPECT/CT images confirmed the biodistribution data. {sup 161}Tb-labelled chCE7 revealed a higher radiotoxicity in nude mice (MTD: 10 MBq) than the {sup 177}Lu-labelled counterpart (MTD: 12 MBq). In a comparative therapy study with equitoxic doses, tumour growth inhibition was better by 82.6 % for the {sup 161}Tb-DOTA-chCE7 than the {sup 177}Lu-DOTA-chCE7 RIT. Our study is the first to show that anti-L1CAM {sup 161}Tb RIT is more effective compared to {sup 177}Lu RIT in ovarian cancer xenografts

  16. Anti-L1CAM radioimmunotherapy is more effective with the radiolanthanide terbium-161 compared to lutetium-177 in an ovarian cancer model

    International Nuclear Information System (INIS)

    The L1 cell adhesion molecule (L1CAM) is considered a valuable target for therapeutic intervention in different types of cancer. Recent studies have shown that anti-L1CAM radioimmunotherapy (RIT) with 67Cu- and 177Lu-labelled internalising monoclonal antibody (mAb) chCE7 was effective in the treatment of human ovarian cancer xenografts. In this study, we directly compared the therapeutic efficacy of anti-L1CAM RIT against human ovarian cancer under equitoxic conditions with the radiolanthanide 177Lu and the potential alternative 161Tb in an ovarian cancer therapy model. Tb was produced by neutron bombardment of enriched 160Gd targets. 161Tb and 177Lu were used for radiolabelling of DOTA-conjugated antibodies. The in vivo behaviour of the radioimmunoconjugates (RICs) was assessed in IGROV1 tumour-bearing nude mice using biodistribution experiments and SPECT/CT imaging. After ascertaining the maximal tolerated doses (MTD) the therapeutic impact of 50 % MTD of 177Lu- and 161Tb-DOTA-chCE7 was evaluated in groups of ten mice by monitoring the tumour size of subcutaneous IGROV1 tumours. The average number of DOTA ligands per antibody was 2.5 and maximum specific activities of 600 MBq/mg were achieved under identical radiolabelling conditions. RICs were stable in human plasma for at least 48 h. 177Lu- and 161Tb-DOTA-chCE7 showed high tumour uptake (37.8-39.0 %IA/g, 144 h p.i.) with low levels in off-target organs. SPECT/CT images confirmed the biodistribution data. 161Tb-labelled chCE7 revealed a higher radiotoxicity in nude mice (MTD: 10 MBq) than the 177Lu-labelled counterpart (MTD: 12 MBq). In a comparative therapy study with equitoxic doses, tumour growth inhibition was better by 82.6 % for the 161Tb-DOTA-chCE7 than the 177Lu-DOTA-chCE7 RIT. Our study is the first to show that anti-L1CAM 161Tb RIT is more effective compared to 177Lu RIT in ovarian cancer xenografts. These results suggest that 161Tb is a promising candidate for future clinical applications in

  17. Synergistic anti-cancer response to chemotherapy and 177Lu-labelled APOMABR radioimmunotherapy in a preclinical model of lung cancer

    International Nuclear Information System (INIS)

    . However, combination of chemotherapy and 177Lu-labelled APOMABR had a synergistic response, resulting in a significant decrease in tumour growth and increased survival of tumour-bearing mice. Bio-distribution analysis revealed that radio-labelled APOMABR targeted tumour tissue, and chemotherapy specifically increased tumour uptake of radio-labelled APOMABR. Importantly, chemotherapy was not associated with increased normal tissue uptake of radio-labelled APOMABR. Conclusions: We have demonstrated both in vitro and in vivo that APOMABR is a dead tumour-cell specific antibody, and that 177Lu-labelled APOMABR is a safe and effective anti-cancer treatment when combined with chemotherapy. Given the safety and efficacy of a single cycle of β-radioimmunotherapy, multiple cycles of treatment, the substitution of an alpha-emitting radionuclide, or both, may provide further benefit and increase the anti-tumour response. (authors)

  18. Practical simplifications for radioimmunotherapy dosimetric models

    Energy Technology Data Exchange (ETDEWEB)

    Shen, S.; DeNardo, G.L.; O`Donnell, R.T.; Yuan, A.; DeNardo, D.A.; Macey, D.J.; DeNardo, S.J. [Univ. of California, Sacramento, CA (United States). Davis Medical Center

    1999-01-01

    Radiation dosimetry is potentially useful for assessment and prediction of efficacy and toxicity for radionuclide therapy. The usefulness of these dose estimates relies on the establishment of a dose-response model using accurate pharmacokinetic data and a radiation dosimetric model. Due to the complexity in radiation dose estimation, many practical simplifications have been introduced in the dosimetric modeling for clinical trials of radioimmunotherapy. Although research efforts are generally needed to improve the simplifications used at each stage of model development, practical simplifications are often possible for specific applications without significant consequences to the dose-response model. In the development of dosimetric methods for radioimmunotherapy, practical simplifications in the dosimetric models were introduced. This study evaluated the magnitude of uncertainty associated with practical simplifications for: (1) organ mass of the MIRD phantom; (2) radiation contribution from target alone; (3) interpolation of S value; (4) macroscopic tumor uniformity; and (5) fit of tumor pharmacokinetic data.

  19. Improved radioimmunotherapy of hematologic malignancies. Final technical report

    Energy Technology Data Exchange (ETDEWEB)

    Press, O.W.

    1996-08-15

    Experiments were performed to study the rates of endocytosis, intracellular routing, and metabolic degradation of radiolabeled monoclonal antibodies targeting tumor-associated antigens on human leukemia and lymphoma cells. An attempt was made to examine in vivo the effects of lysosomotropic amines and thioamides on the retention of radiolabeled monoclonal antibodies by tumor cells. Experiments also examined the impact of newer radioiodination techniques on the metabolic degradation of radioiodinated antibodies, and on the radioimmunoscintigraphy and radioimmunotherapy of neoplasms. The endocytosis, intracellular routing, and degradation of radioimmunoconjugates prepared with I-131, In-111, and Y-90 were compared. The utility of radioimmunoconjugates targeting oncogene products for the radioimmunotherapy and radioimmunoscintigraphy of cancer was investigated.

  20. Improved radioimmunotherapy of hematologic malignancies. Final technical report

    International Nuclear Information System (INIS)

    Experiments were performed to study the rates of endocytosis, intracellular routing, and metabolic degradation of radiolabeled monoclonal antibodies targeting tumor-associated antigens on human leukemia and lymphoma cells. An attempt was made to examine in vivo the effects of lysosomotropic amines and thioamides on the retention of radiolabeled monoclonal antibodies by tumor cells. Experiments also examined the impact of newer radioiodination techniques on the metabolic degradation of radioiodinated antibodies, and on the radioimmunoscintigraphy and radioimmunotherapy of neoplasms. The endocytosis, intracellular routing, and degradation of radioimmunoconjugates prepared with I-131, In-111, and Y-90 were compared. The utility of radioimmunoconjugates targeting oncogene products for the radioimmunotherapy and radioimmunoscintigraphy of cancer was investigated

  1. Intraperitoneal alpha-radioimmunotherapy in mice using different specific activities

    DEFF Research Database (Denmark)

    Elgqvist, Jörgen; Andersson, Håkan; Haglund, Elin; Jensen, Holger; Kahu, Helena; Lindegren, Sture; Warnhammar, Elisabet; Hultborn, Ragnar

    2009-01-01

    The aim of this study was to investigate the therapeutic efficacy of the alpha-radioimmunotherapy of ovarian cancer in mice, using different specific activities. This study was performed by using the monoclonal antibody, MX35 F(ab')(2), labeled with the alpha-particle-emitter, 211At....

  2. Theranostic pretargeted radioimmunotherapy of colorectal cancer xenografts in mice using picomolar affinity 86Y- or 177Lu-DOTA-Bn binding scFv C825/GPA33 IgG bispecific immunoconjugates

    International Nuclear Information System (INIS)

    GPA33 is a colorectal cancer (CRC) antigen with unique retention properties after huA33-mediated tumor targeting. We tested a pretargeted radioimmunotherapy (PRIT) approach for CRC using a tetravalent bispecific antibody with dual specificity for GPA33 tumor antigen and DOTA-Bn-(radiolanthanide metal) complex. PRIT was optimized in vivo by titrating sequential intravenous doses of huA33-C825, the dextran-based clearing agent, and the C825 haptens 177Lu-or 86Y-DOTA-Bn in mice bearing the SW1222 subcutaneous (s.c.) CRC xenograft model. Using optimized PRIT, therapeutic indices (TIs) for tumor radiation-absorbed dose of 73 (tumor/blood) and 12 (tumor/kidney) were achieved. Estimated absorbed doses (cGy/MBq) to tumor, blood, liver, spleen, and kidney for single-cycle PRIT were 65.8, 0.9 (TI 73), 6.3 (TI 10), 6.6 (TI 10), and 5.3 (TI 12), respectively. Two cycles of PRIT (66.6 or 111 MBq 177Lu-DOTA-Bn) were safe and effective, with a complete response of established s.c. tumors (100 - 700 mm3) in nine of nine mice, with two mice alive without recurrence at >140 days. Tumor log kill in this model was estimated to be 2.1 - 3.0 based on time to 500-mm3 tumor recurrence. In addition, PRIT dosimetry/diagnosis was performed by PET imaging of the positron-emitting DOTA hapten 86Y-DOTA-Bn. We have developed anti-GPA33 PRIT as a triple-step theranostic strategy for preclinical detection, dosimetry, and safe targeted radiotherapy of established human colorectal mouse xenografts. (orig.)

  3. Theranostic pretargeted radioimmunotherapy of colorectal cancer xenografts in mice using picomolar affinity {sup 86}Y- or {sup 177}Lu-DOTA-Bn binding scFv C825/GPA33 IgG bispecific immunoconjugates

    Energy Technology Data Exchange (ETDEWEB)

    Cheal, Sarah M.; Lee, Sang-gyu; Punzalan, Blesida; Larson, Steven M. [Memorial Sloan Kettering Cancer Center, Department of Radiology, New York, NY (United States); Memorial Sloan Kettering Cancer Center, Molecular Pharmacology and Chemistry Program, New York, NY (United States); Xu, Hong; Guo, Hong-fen [Memorial Sloan Kettering Cancer Center, Department of Pediatrics, New York, NY (United States); Chalasani, Sandhya; Carrasquillo, Jorge A. [Memorial Sloan Kettering Cancer Center, Department of Radiology, New York, NY (United States); Fung, Edward K. [Memorial Sloan Kettering Cancer Center, Molecular Pharmacology and Chemistry Program, New York, NY (United States); Memorial Sloan Kettering Cancer Center, Department of Medical Physics, New York, NY (United States); Jungbluth, Achim [Memorial Sloan Kettering Cancer Center, Department of Pathology, New York, NY (United States); Zanzonico, Pat B.; O' Donoghue, Joseph [Memorial Sloan Kettering Cancer Center, Department of Medical Physics, New York, NY (United States); Smith-Jones, Peter M. [Stony Brook University, Department of Psychiatry and Behavioral Science, Stony Brook, NY (United States); Stony Brook University, Department of Radiology, Stony Brook, NY (United States); Wittrup, K.D. [Massachusetts Institute of Technology, Department of Chemical Engineering, Cambridge, MA (United States); Massachusetts Institute of Technology, Department of Biological Engineering, Cambridge, MA (United States); Massachusetts Institute of Technology, Koch Institute for Integrative Cancer Research, Cambridge, MA (United States); Cheung, Nai-Kong V. [Memorial Sloan Kettering Cancer Center, Molecular Pharmacology and Chemistry Program, New York, NY (United States); Memorial Sloan Kettering Cancer Center, Department of Pediatrics, New York, NY (United States)

    2016-05-15

    GPA33 is a colorectal cancer (CRC) antigen with unique retention properties after huA33-mediated tumor targeting. We tested a pretargeted radioimmunotherapy (PRIT) approach for CRC using a tetravalent bispecific antibody with dual specificity for GPA33 tumor antigen and DOTA-Bn-(radiolanthanide metal) complex. PRIT was optimized in vivo by titrating sequential intravenous doses of huA33-C825, the dextran-based clearing agent, and the C825 haptens {sup 177}Lu-or {sup 86}Y-DOTA-Bn in mice bearing the SW1222 subcutaneous (s.c.) CRC xenograft model. Using optimized PRIT, therapeutic indices (TIs) for tumor radiation-absorbed dose of 73 (tumor/blood) and 12 (tumor/kidney) were achieved. Estimated absorbed doses (cGy/MBq) to tumor, blood, liver, spleen, and kidney for single-cycle PRIT were 65.8, 0.9 (TI 73), 6.3 (TI 10), 6.6 (TI 10), and 5.3 (TI 12), respectively. Two cycles of PRIT (66.6 or 111 MBq {sup 177}Lu-DOTA-Bn) were safe and effective, with a complete response of established s.c. tumors (100 - 700 mm{sup 3}) in nine of nine mice, with two mice alive without recurrence at >140 days. Tumor log kill in this model was estimated to be 2.1 - 3.0 based on time to 500-mm{sup 3} tumor recurrence. In addition, PRIT dosimetry/diagnosis was performed by PET imaging of the positron-emitting DOTA hapten {sup 86}Y-DOTA-Bn. We have developed anti-GPA33 PRIT as a triple-step theranostic strategy for preclinical detection, dosimetry, and safe targeted radiotherapy of established human colorectal mouse xenografts. (orig.)

  4. Chemotherapy synergizes with radioimmunotherapy targeting La autoantigen in tumors.

    Directory of Open Access Journals (Sweden)

    Fares Al-Ejeh

    Full Text Available BACKGROUND: To date, inefficient delivery of therapeutic doses of radionuclides to solid tumors limits the clinical utility of radioimmunotherapy. We aim to test the therapeutic utility of Yttrium-90 ((90Y-radio-conjugates of a monoclonal antibody, which we showed previously to bind specifically to the abundant intracellular La ribonucleoprotein revealed in dead tumor cells after DNA-damaging treatment. METHODOLOGY/PRINCIPAL FINDINGS: Immunoconjugates of the DAB4 clone of the La-specific monoclonal antibody, APOMAB, were prepared using the metal chelator, 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA, and then radiolabeled with (90Y. Mice bearing established subcutaneous tumors were treated with (90Y-DOTA-DAB4 alone or after chemotherapy. Non-radiosensitizing cyclophosphamide/etoposide chemotherapy was used for the syngeneic EL4 lymphoma model. Radiosensitizing cisplatin/gemcitabine chemotherapy was used for the syngeneic Lewis Lung carcinoma (LL2 model, and for the xenograft models of LNCaP prostatic carcinoma and Panc-1 pancreatic carcinoma. We demonstrate the safety, specificity, and efficacy of (90Y-DOTA-DAB4-radioimmunotherapy alone or combined with chemotherapy. EL4 lymphoma-bearing mice either were cured at higher doses of radioimmunotherapy alone or lower doses of radioimmunotherapy in synergy with chemotherapy. Radioimmunotherapy alone was less effective in chemo- and radio-resistant carcinoma models. However, radioimmunotherapy synergized with radiosensitizing chemotherapy to retard significantly tumor regrowth and so prolong the survival of mice bearing LL2, LNCaP, or Panc-1 subcutaneous tumor implants. CONCLUSIONS/SIGNIFICANCE: We report proof-of-concept data supporting a unique form of radioimmunotherapy, which delivers bystander killing to viable cancer cells after targeting the universal cancer antigen, La, created by DNA-damaging treatment in neighboring dead cancer cells. Subsequently we propose that DAB4

  5. Differentiation of irradiation and cetuximab induced skin reactions in patients with locally advanced head and neck cancer undergoing radioimmunotherapy: the HICARE protocol (Head and neck cancer: ImmunoChemo and Radiotherapy with Erbitux) – a multicenter phase IV trial

    International Nuclear Information System (INIS)

    In order to improve the clinical outcome of patients with locally advanced squamous cell carcinoma of the head and neck (LASCCHN) not being capable to receive platinum-based chemoradiation, radiotherapy can be intensified by addition of cetuximab, a monoclonal antibody that blocks the epidermal growth factor receptor (EGFR). The radioimmunotherapy with cetuximab is a feasible treatment option showing a favourable toxicity profile. The most frequent side effect of radiotherapy is radiation dermatitis, the most common side effect of treatment with cetuximab is acneiform rash. Incidence and severity of these frequent, often overlapping and sometimes limiting skin reactions, however, are not well explored. A clinical and molecular differentiation between radiogenic skin reactions and skin reactions caused by cetuximab which may correlate with outcome, have never been described before. The HICARE study is a national, multicenter, prospective phase IV study exploring the different types of skin reactions that occur in patients with LASCCHN undergoing radioimmun(chemo)therapy with the EGFR inhibitor cetuximab. 500 patients with LASCCHN will be enrolled in 40 participating sites in Germany. Primary endpoint is the rate of radiation dermatitis NCI CTCAE grade 3 and 4 (v. 4.02). Radioimmunotherapy will be applied according to SmPC, i.e. cetuximab will be administered as loading dose and then weekly during the radiotherapy. Irradiation will be applied as intensity-modulated radiation therapy (IMRT) or 3D-dimensional radiation therapy. The HICARE trial is expected to be one of the largest trials ever conducted in head and neck cancer patients. The goal of the HICARE trial is to differentiate skin reactions caused by radiation from those caused by the monoclonal antibody cetuximab, to evaluate the incidence and severity of these skin reactions and to correlate them with outcome parameters. Besides, the translational research program will help to identify and confirm novel

  6. Selection of monoclonal antibody E48 IgG or U36 IgG for adjuvant radioimmunotherapy in head and neck cancer patients.

    OpenAIRE

    van Bree, R.; Roos, J C; Plaizier, M. A.; Quak, J.J.; Van Kamp, G J; den Hollander, W.; Snow, G. B.; van Dongen, G. A.

    1997-01-01

    Preliminary data from recent clinical radioimmunoscintigraphy studies indicate that 99mTc-labelled murine monoclonal antibodies (MAbs) E48 and U36 have a similar ability to target squamous cell carcinoma of the head and neck (HNSCC) selectively. In the present study we describe additional aspects of murine and chimeric MAb (mMAb and cMAb) E48 and U36, which might influence the selection of one MAb for adjuvant radioimmunotherapy. To make direct comparison possible, ten patients received 11.2 ...

  7. Improvement of radioimmunotherapy using pretargeting

    Directory of Open Access Journals (Sweden)

    Eric eFrampas

    2013-06-01

    Full Text Available During the past two decades, considerable research has been devoted to radionuclide therapy using radiolabelled monoclonal antibodies and receptor binding agents. Conventional Radioimmunotherapy (RIT is now an established and important tool in the treatment of hematologic malignancies such as Non-Hodgkin lymphoma. For solid malignancies, the efficacy of RIT has not been as successful due to lower radiosensitivity, difficult penetration of the antibody into the tumor and potential excessive radiation to normal tissues. Innovative approaches have been developed in order to enhance tumor absorbed dose while limiting toxicity to overcome the different limitations due to the tumor and host characteristics.Pretargeting techniques (pRIT are a promising approach that consists of decoupling the delivery of a tumor monoclonal antibody (mAb from the delivery of the radionuclide. This results in a much higher tumor-to-normal tissue ratio and is favorable for therapy as well and imaging. This includes various strategies based on avidin/streptavidin-biotin, DNA-complementary DNA and bispecific antibody-hapten bindings. PRIT continuously evolves with the investigation of new molecular constructs and the development of radiochemistry. Pharmacokinetics improve dosimetry depending on the radionuclides used (alpha, beta and Auger emitters with prediction of tumor response and host toxicities. New constructs such as the Dock and Lock technology allow production of a variety of mABs directed against tumor-associated antigens. Survival benefit has already been shown in medullary thyroid carcinoma. Improvement in delivery of radioactivity to tumors with these pretargeting procedures associated with reduced hematologic toxicity will become the next generation of RIT. The following review addresses actual technical and clinical considerations and future development of pRIT.

  8. Chemo radioimmunotherapy with 5-fluorouracil, cisplatin and interferon-{alpha} in pancreatic and peri-ampullary cancer: Results of a feasibility study; Chimioradiotherapie et immunotherapie avec 5-fluoro-uracile, cisplatine et interferon-{alpha} dans les cancers du pancreas et periampullaires: resultats d'une etude de faisabilite

    Energy Technology Data Exchange (ETDEWEB)

    Nitsche, M.; Christiansen, H.; Hermann, R.M.; Hess, C.F. [Goettingen Univ., Dept. of Radiation Oncology (Germany); Horstmann, O.; Becker, H. [Goettingen Univ., Dept. of Surgery (Germany); Pradier, O. [Centre Hospitalier Universitaire, Dept. de cancerologie, 29 - Brest (France); Schmidberger, H. [Mainz Univ., Dept. of Radiation Oncology (Germany)

    2008-12-15

    Background: Recent studies give rise to the hypothesis, that adjuvant chemo radioimmunotherapy with 5-fluorouracil (5-F.U.), cisplatin and interferon-a (I.F.N.-a) might be a possible new treatment of pancreatic cancer in resected patients. We report the up-to-now experience at our institution. Patients and methods: Eleven patients with histological diagnosis of localized carcinoma of the pancreas (n = 7) or peri-ampullary (n = 4) were prospectively analyzed. Four patients were deemed unresectable because of local invasion of adjacent organs (neo-adjuvant setting) and seven patients underwent curative resection (adjuvant setting). Eight patients were classified as T3 carcinomas and three T4 carcinomas. Fifty-five per cent (6/11) of the patients presented with positive lymph node involvement. One histological Grade I, six Grade II and three Grade III were detected. External conformal irradiation to a total dose of 50.4 Gy with 1.8 Gy per day was delivered. All patients received a concomitant chemotherapy with continuous 5-F.U. 200 mg/m{sup 2} per day on 28 treatment days and intravenous bolus cisplatin 30 mg/m{sup 2} per week (Day 2, 9, 16, 23, 30). A recombinant r-I.F.N.-a was administered on three days weekly during Week one to five of the radiotherapy course as subcutaneous injections with 3*3 Mio. I.U. weekly. Results: The four-year overall survival rate for all patients was 55%. In the neo-adjuvant group, three of four patients died due to progressive disease; in the adjuvant group, combined chemo radioimmunotherapy lead to controlled disease in five of seven patients. The overall toxicity was well-managed. Conclusion: Our data strengthens the hypothesis of concomitant chemo radioimmunotherapy with 5-F.U., I.F.N.-a and cisplatin as a possible new treatment of pancreatic cancer in resected patients. (authors)

  9. Radioimmunotherapy Using Vascular Targeted 213Bi: The Role of TNF-Alpha in the Development of Pulmonary Fibrosis

    Energy Technology Data Exchange (ETDEWEB)

    Davis, I.A.; Kennel, S.J.

    1998-10-14

    A monoclonal antibody (201B) specific to murine thrombomodulin, covalently linked to CHX-b-DTPA, successfully delivers chelated 213Bi, an {alpha}-particle emitter, (213Bi-201B) rapidly to lungvascular endothelium. When injected at doses of l MBq/mouse, 213Bi-201B destroyed most of the 100 colonies of EMT-6 mammary carcinomas growing as lung tumors of up to 2000 cells/colony. Some mice were cured of lung tumors and others had extended life-spans compared to untreated control animals but eventually succumbed to tumor recurrence. At injected doses of 4-6 MBq/mouse, 100% of lung tumor colonies were eliminated; however, 3-4 months later these mice developed pulmonary fibrosis and died. The mechanisms leading to the fibrotic response in other pulmonary irradiation models strongly implicate tumor necrosis factor-alpha (TNF-{alpha}), released from damaged tissues, as the pivotal inflammatory cytokine in a cascade of events which culminate in fibrosis. Attempts to prevent the development of pulmonary fibrosis, by using antibodies or soluble receptor (Enbrel{trademark}) as inhibitors of TNF-{alpha}, were unsuccessful. Additionally, mice genetically deficient for TNF-{alpha} production developed pulmonary fibrosis following 213Bi-201B treatment. Interestingly, non-tumor bearing BALB/c mice receiving Enbrel{trademark} or mice genetically deficient in TNF-{alpha} production and treated with 213Bi-201B, had significantly reduced life spans compared to mice receiving no treatment or 213Bi-201B alone. We speculate that, in normal mice, while TNF-{alpha} may induce an inflammatory response following {alpha}-particle radiation mediated tumor clearance and pulmonary damage, its effects in the post-tumor clearance time period may actually retard the development of fibrosis.

  10. Ongoing investigations and new uses of radioimmunotherapy in the treatment of non-Hodgkin's lymphoma

    International Nuclear Information System (INIS)

    Studies in radiation oncology are focusing on the optimal use of systemic targeted radionuclide therapy (STaRT) in the treatment of patients with cancer. The two approved radioimmunotherapy agents, yttrium-90 ibritumomab tiuxetan and iodine-131 tositumomab, are being studied in a range of lymphoid malignancies, from low-grade to aggressive B-cell non-Hodgkin's lymphomas. Studies of standard- and escalated-dose radioimmunotherapy with or without stem cell support are reviewed, as are radioimmunotherapy with other therapeutic modalities in these settings. The results of these trials have important implications for clinical practice, and it is hoped that they will further clarify the optimal timing and dosing of these agents

  11. Radioimmunotherapy of infection with 213Bi-labeled antibodies

    OpenAIRE

    Dadachova, Ekaterina

    2008-01-01

    Bismuth-213 (213Bi) (physical half-life 46 min) is a beta-emitter (97%) and an alpha-emitter (3%) which decays to short lived alpha-emitter Polonium-213 and could therefore be used as an in vivo generator of alpha particles with the energy of around 8 MeV. 213Bi has been successfully used during the last decade in both clinical and pre-clinical work for radioimmunotherapy (RIT) of cancer with 213Bi-labeled monoclonal antibodies (mAbs). RIT has been proposed as a novel techonology for treatmen...

  12. Radioimmunotherapy

    Science.gov (United States)

    ... used to treat: non-Hodgkin B-cell lymphoma (NHL), including both new patients and patients who have ... is generally not administered to pregnant women and children. Pre-screening of patients will occur to ensure ...

  13. A pretargeting system for tumor PET imaging and radioimmunotherapy

    Directory of Open Access Journals (Sweden)

    Françoise eKraeber-Bodéré

    2015-03-01

    Full Text Available Labeled antibodies, as well as their fragments and antibody-derived recombinant constructs, have long been proposed as general vectors to target radionuclides to tumor lesions for imaging and therapy. They have indeed shown promise in both imaging and therapeutic applications, but they have not fulfilled the original expectations of achieving sufficient image contrast for tumor detection or sufficient radiation dose delivered to tumors for therapy. Pretargeting was originally developed for tumor immunoscintigraphy. It was assumed that directly-radiolabled antibodies could be replaced by an unlabeled immunoconjugate capable of binding both a tumor-specific antigen and a small molecular weight molecule. The small molecular weight molecule would carry the radioactive payload and would be injected after the bispecific immunoconjugate. It has been demonstrated that this approach does allow for both antibody-specific recognition and fast clearance of the radioactive molecule, thus resulting in improved tumor-to-normal tissue contrast ratios. It was subsequently shown that pretargeting also held promise for tumor therapy, translating improved tumor-to-normal tissue contrast ratios into more specific delivery of absorbed radiation doses. Many technical approaches have been proposed to implement pretargeting, and two have been extensively documented. One is based on the avidin-biotin system, and the other on bispecific antibodies binding a tumor-specific antigen and a hapten. Both have been studied in preclinical models, as well as in several clinical studies, and have shown improved targeting efficiency. This article reviews the historical and recent preclinical and clinical advances in the use of bispecific-antibody-based pretargeting for radioimmunodetection and radioimmunotherapy of cancer. The results of recent evaluation of pretargeting in PET imaging also are discussed.

  14. Radioimmunotherapy for Treatment of Acute Leukemia.

    Science.gov (United States)

    Bodet-Milin, Caroline; Kraeber-Bodéré, Françoise; Eugène, Thomas; Guérard, François; Gaschet, Joëlle; Bailly, Clément; Mougin, Marie; Bourgeois, Mickaël; Faivre-Chauvet, Alain; Chérel, Michel; Chevallier, Patrice

    2016-03-01

    Acute leukemias are characterized by accumulation of immature cells (blasts) and reduced production of healthy hematopoietic elements. According to the lineage origin, two major leukemias can be distinguished: acute myeloid leukemia (AML) and acute lymphoid leukemia (ALL). Although the survival rate for pediatric ALL is close to 90%, half of the young adults with AML or ALL and approximately 90% of older patients with AML or ALL still die of their disease, raising the need for innovative therapeutic approaches. As almost all leukemic blasts express specific surface antigens, targeted immunotherapy appears to be particularly promising. However, published results of immunotherapy alone are generally modest. Radioimmunotherapy (RIT) brings additional therapeutic mechanisms using radiolabeled monoclonal antibodies (mAbs) directed to tumor antigens, thus adding radiobiological cytotoxicity to immunologic cytotoxicity. Because of the high radiosensitivity of tumor cells and the diffuse widespread nature of the disease, making it rapidly accessible to circulating radiolabeled mAbs, acute leukemias represent relevant indications for RIT. With the development of recombinant and humanized mAbs, innovative radionuclides, and more efficient radiolabeling and pretargeting techniques, RIT has significantly improved over the last 10 years. Different approaches of α and β RIT targeting CD22, CD33, CD45, or CD66 antigens have already been evaluated or are currently being developed in the treatment of acute leukemia. This review summarizes the preclinical and clinical studies demonstrating the potential of RIT in treatment of AML and ALL. PMID:26897718

  15. Radiolabeled bivalent haptens for tumor immunodetection and radioimmunotherapy

    Energy Technology Data Exchange (ETDEWEB)

    Gruaz-Guyon, A.; Janevik-Ivanovska, E.; Raguin, O. [Hopital Saint-Antoine, Faculte' de Medecine, Paris (France); De Labriolle-Vaylet, C. [Hopital Saint-Antoine, Faculte' de Medecine, Paris (France); Hopital Saint-Antoine, Service de Medecine Nucleaire, Paris (France); Barbet, J. [Universite' de la Mediterranee, Faculte' de Medecine, Marseille (France)

    2001-06-01

    The pre targeting technique referred to as the Affinity Enhancement System (AES) uses bispecific antibodies and radiolabeled bivalent haptens that bind cooperatively to target cells in vivo. Experimental and clinical data demonstrate that DTPA bivalent haptens can deliver large radiation doses to tumor cells with high tumor to normal tissue contrast ratios and long activity residence time in tumors. Preliminary clinical results of radioimmunotherapy of medullary thyroid carcinomas and lung cancers look promising. Very encouraging results in biodistribution and radioimmunotherapy experiments in animals have been obtained with new haptens bearing two histamine-hemisuccinate suitable for {sup 131}I, {sup 99m}Tc and {sup 188}Re labeling. Targeting isotopes to double antigen positive tumor cells provides a binding enhancement that increases specificity for tumor cells as compared to single antigen targeting on normal cells. This approach may be beneficial for targeting isotopes to B type acute lymphoblastic leukemia and Burkitt lymphoma, as well as others tumors co-expressing two markers of low specificity, and might increase tumor irradiation with minimal irradiation of normal cells.

  16. Radioimmunotherapy from an AIEA perspective

    International Nuclear Information System (INIS)

    Full text of publication follows. The role of International Atomic Energy Agency (IAEA) is to promote pacific applications of nuclear energy and radioactivity that may help to improve the economic and social levels in Member States. In this respect, the improvement of national health care systems through the introduction of new diagnostic and therapeutic approaches developed within the field of nuclear medicine is one of its major goals. Finding effective cancer treatments is still at the forefront of IAEA projects due to the global impact of this disease. At the most fundamental level, cancer can be viewed as a perfect example of 'molecular disease' originating when the inner biochemical fabric of the cell is abnormally altered. It is exactly the complexity of this molecular machinery that makes the understanding and treatment of cancer so difficult. However, in the search for a consistent therapeutic approach, this basic molecular paradigm cannot be escaped. In this context, radionuclide therapy employing single-molecule radiolabelled substances still constitutes a promising tool for cancer treatment due to its intrinsic molecular nature. Radionuclide therapy is unique in its ability to deliver selectively to cancerous cells a therapeutic dose of radioactivity by means of rationally designed molecular carriers. Thus, a key advantage of molecular radionuclide therapy is that it does not need to achieve the full molecular picture, but just some relevant piece of the entire puzzle that may allow targeting selectively tumour cells. The major challenge is to find a perfect matching between the molecular properties of a radiolabeled agent and a relevant bio-molecular mechanism capable of uploading the required amount of radioactivity at the tumour site. In this respect, iodine-131 based therapy still remains a unique, unmatched example. IAEA is constantly promoting projects and scientific discussions on the applications of therapeutic radiopharmaceuticals in

  17. Developments in Colorectal Cancer Screening

    Science.gov (United States)

    ... on. Feature: Colorectal Cancer Developments in Colorectal Cancer Screening Summer 2016 Table of Contents Dr. Asad Umar, ... know to help determine the best colon cancer screening test for them? Colonoscopy is considered the gold ...

  18. The radiolabeled monoclonal antibodies in immunoscintigraphy and radioimmunotherapy: current state and perspectives

    International Nuclear Information System (INIS)

    The antibodies can be satisfactorily labelled with technitium-99 m or indium-111 for tumor immunoscintigraphy. The immunoscintigraphy is not useful for the primary tumor diagnosis. It can be useful for the diagnosis of the some cancer extension and for recurrent tumor visualization. The immunoscintigraphy is widely competed with Positron Emission Tomography (PET) which gives accurate results. In the future the immunoscintigraphy, in pre-therapeutic stage, contribute to the estimation of the dose delivered to the tumor and to normal organs for adopting or not a radioimmunotherapy. The antibodies can also be labeled with Iodine-131 for an application in radioimmunotherapy (RIT). The RIT is efficient in the non-Hodgkin's lymphoma treatment because of their great radiosensitivity. Until now the results have been very modest in solid tumor treatment but methodological and biotechnological progresses have to improve the efficiency especially for the small tumors. In the future iodine-131 which requires the confinement (very expensive) of patients will be substituted by yttrium-90 beta emitter, more energetic than iodine-131 and can be injected in walking case. In the long term, the alpha emitter radionuclides (astatine-211 or bismuth-213) can be used for hematologic cancer treatment. In conclusion the future of radiolabeled monoclonal antibodies is essentially therapeutic. The radioimmunotherapy associated to the chemotherapy give promising perspectives for the radiosensitive cancer treatment and in general small solid tumor treatment (F.M.)

  19. Radioimmunotherapy of non-Hodgkin's lymphoma

    International Nuclear Information System (INIS)

    Non-Hodgkin's lymphomas (NHL) are malignancies derived from lymphocytes with approximately 80% involving B-cell lymphocytes and 95% of B-cell lymphomas expressing the CD20 antigen on the tumor cell surface membrane. Although NHL is considered a curable disease, many patients especially those with indolent NHL relapse and eventually die. For patients with limited stage disease, conventional radiation therapy is utilized. For advanced stage disease combination chemotherapy and Rituximab, a chimeric anti-CD20 monoclonal antibody is the standard therapy. Radioimmunotherapy is a recent addition for treatment of NHL and utilizes a tumor cell targeting monoclonal antibody chemically linked to a therapeutic radionuclide delivering radiation to tumor cells while limiting toxicity to normal cells. The advantage of radioimmunotherapy is the ability to treat multiple tumor sites throughout the body following intravenous infusion. The most common radionuclides used for radioimmunotherapy have been 131Iodine (I-131) and more recently 90Yttrium (Y-90). Y-90 is bound to the monoclonal antibody using metal chelating groups while I-131 is directly linked to the antibody. Phase I, II and III therapy trials of I-131 or Y-90 labeled anti-CD20 monoclonal antibodies have shown radioimmunotherapy to be safe and highly effective in the treatment of B-cell NHL. Transient hematologic toxicity with nadirs occurring at 7 to 9 weeks and lasting approximately 1 to 2 weeks has been the only side-effects. The response rates from radioimmunotherapy have been higher than for the unlabeled antibody therapy (Y-90 anti-CD20 vs. Rituximab response rates = 80% vs. 56% ( p = 0.002) and complete response (CR) rates were 30% and 16% respectively (p=0.04). Radiolabeled anti-CD20 monoclonal antibodies are now being used alone or in combination with chemotherapy, external beam radiation or stem cell transplantation for treating patients with NHL. Radioimmunotherapy has become a value new treatment for patients

  20. Mechanism and energetics for complexation of 90Y with 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA), a model for cancer radioimmunotherapy

    International Nuclear Information System (INIS)

    A promising cancer therapy involves the use of the macrocyclic polyaminoacetate DOTA (1,4,6,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid) attached to a tumor-targeting antibody complexed with the β emitter 90Y3+. However, incorporation of the 90Y into the DOTA conjugate is too slow. To identify the origins of this problem, ab initio quantum chemistry methods (B3LYP/:ACVP* and HF/LACVP*) were used to predict structures and energetics. The authors find that the initial complex YH2(DOTA)+ is 4-coordinate (the four equivalent carboxylate oxygens), which transforms to YH(DOTA) (5-coordinate with one ring N and four carboxylate oxygens), and finally to Y(DOTA)-, which is 8-coordinate (four oxygens and four nitrogens). The rate-determining step is the conversion of YH(DOTA) to Y(DOTA)-, which was calculated to have an activation free energy (aqueous phase) of 8.4 kcal/mol, in agreement with experimental results (8.1--9.3 kcal/mol) for various metals to DOTA [Kumar, K.; Tweedle, M.F. Inorg. Chem. 1993, 32, 4193--4199; Wu, S.L.; Horrocks, W.D., Jr., Inorg. Chem. 1995, 34, 3724--2732]. On the basis of this mechanism the authors propose a modified chelate, DO3AlPr, which has calculated at a much faster rate of incorporation

  1. Research about the radioimmunotherapy of fungal infection

    International Nuclear Information System (INIS)

    The wide use of the broad-spectrum antibiotics, corticosteroids and immunosuppressant may lead to lower immunity which can increases the chance of fungi infection. Searching a better antifungal therapy is one of the direction of medical research. Ionizing radiation can quickly and effectively kill the microorganisms, and also can be the antifungal. The research suggests that the method of targeting radioimmunotherapy labeled specific antibody may become an effective antifungal treatment channels. (authors)

  2. Towards Personalized Cancer Therapy : New Diagnostic Biomarkers and Radiosensitization Strategies

    OpenAIRE

    Spiegelberg, Diana

    2015-01-01

    This thesis focuses on the evaluation of biomarkers for radio-immunodiagnostics and radio-immunotherapy and on radiosensitization strategies after HSP90 inhibition, as a step towards more personalized cancer medicine. There is a need to develop new tracers that target cancer-specific biomarkers to improve diagnostic imaging, as well as to combine treatment strategies to potentiate synergistic effects. Special focus has been on the cell surface molecule CD44 and its oncogenic variants, which w...

  3. Development of cancer immunotherapy

    International Nuclear Information System (INIS)

    To increase the curative rate of cancer patients, we developed ideal biological response modifier from medicinal plants: Ginsan, KC68IId-8, KC-8Ala, KG-30. Ginsan activated natural killer cell activity of spleen cells more than 5.4 times than lentinan, 1.4 times than picibanil. Radioprotective activity of Ginsan is stronger than WR2721, glucan, and selenium. The immunogenicity of MOPC tumor cells was augmented by treatment with IL-10 antisense oligonucleotide and by transfection with VEGF sense-, antisense gene. The immunogenicity of MOPC tumor cells was augmented by treatment with IL-10 antisense oligonucleotide and by transfection with VEGF sense-, antisense gene. The immunogenicity of A20 tumor cells was also augmented by transfection with B7.1 gene. The immunosuppression of gamma-irradiation was due to the reduction of Th1 sytokine gene expression through STAT pathway. These research will devote to develop new cancer immunotherapy and to reduce side effect of cancer radiotherapy and chemotherapy

  4. Development of cancer immunotherapy

    Energy Technology Data Exchange (ETDEWEB)

    Yun, Yeon Sook; Chung, H. Y.; Yi, S. Y.; Kim, K. W.; Kim, B. K.; Chung, I. S.; Park, J. Y

    1999-04-01

    To increase the curative rate of cancer patients, we developed ideal biological response modifier from medicinal plants: Ginsan, KC68IId-8, KC-8Ala, KG-30. Ginsan activated natural killer cell activity of spleen cells more than 5.4 times than lentinan, 1.4 times than picibanil. Radioprotective activity of Ginsan is stronger than WR2721, glucan, and selenium. The immunogenicity of MOPC tumor cells was augmented by treatment with IL-10 antisense oligonucleotide and by transfection with VEGF sense-, antisense gene. The immunogenicity of MOPC tumor cells was augmented by treatment with IL-10 antisense oligonucleotide and by transfection with VEGF sense-, antisense gene. The immunogenicity of A20 tumor cells was also augmented by transfection with B7.1 gene. The immunosuppression of gamma-irradiation was due to the reduction of Th1 sytokine gene expression through STAT pathway. These research will devote to develop new cancer immunotherapy and to reduce side effect of cancer radiotherapy and chemotherapy.

  5. Role of chelates in treatment of cancer

    Directory of Open Access Journals (Sweden)

    Tripathi Laxmi

    2007-01-01

    Full Text Available Chelates are used in cancer as cytotoxic agent, as radioactive agent in imaging studies and in radioimmunotherapy. Various chelates based on ruthenium, copper, zinc, organocobalt, gold, platinum, palladium, cobalt, nickel and iron are reported as cytotoxic agent. Monoclonal antibodies labeled with radioactive metals such as yttrium-90, indium-111 and iodine-131 are used in radioimmunotherapy. This review is an attempt to compile the use of chelates as cytotoxic drugs and in radioimmunotherapy.

  6. Standard Operating Procedure for In-house Preparation of (131)I-rituximab for Radioimmunotherapy of Non-Hodgkin's Lymphoma.

    Science.gov (United States)

    Pickford, Matthew D; Turner, J Harvey

    2012-09-01

    A Standard Operating Procedure (SOP) has been formulated for in-house preparation, quality control, dispensing and administration of (131)I-rituximab appropriate for the safe, effective, radioimmunotherapy of non-Hodgkin lymphoma. A decade of experience of semi-automated radioiodination of rituximab in our hospital radiopharmaceutical laboratory was analysed. The methodology was then refined for safe, practical, affordable application to radioimmunotherapy of lymphoma in departments of nuclear medicine in developing countries. This SOP has the potential to be incorporated into good laboratory practice conditions appropriate for local regulatory agency requirements. PMID:23372447

  7. Design and manufacture of monoclonal antibodies for radioimmunotherapy

    International Nuclear Information System (INIS)

    Appropriate design and manufacture of monoclonal antibodies is fundamental to their use for radioimmunotherapy. Besides the right selection of antibody specificity and affinity, recombinant antibodies can be designed to simplify manufacture and minimise unwanted side effects. Although many innovative new technologies have been developed in recent years, antibodies are still most commonly produced from mammalian cells and purified by column chromatography. Purification methods have to be designed and validated to remove potential contaminants, especially retroviruses which in principle might be present in mammalian cell lines. Adherence to relevant Good Manufacturing Practice is mandatory in the production of any medicinal product and there are numerous guidelines regarding the manufacture of antibodies. This article outlines some methods used for fermentation, purification and quality control of antibodies intended for radiolabelling

  8. Melanoma stem cells in experimental melanoma are killed by radioimmunotherapy

    International Nuclear Information System (INIS)

    Introduction: In spite of recently approved B-RAF inhibitors and immunomodulating antibodies, metastatic melanoma has poor prognosis and novel treatments are needed. Melanoma stem cells (MSC) have been implicated in the resistance of this tumor to chemotherapy. Recently we demonstrated in a Phase I clinical trial in patients with metastatic melanoma that radioimmunotherapy (RIT) with 188-Rhenium(188Re)-6D2 antibody to melanin was a safe and effective modality. Here we investigated the interaction of MSC with RIT as a possible mechanism for RIT efficacy. Methods: Mice bearing A2058 melanoma xenografts were treated with either 1.5 mCi 188Re-6D2 antibody, saline, unlabeled 6D2 antibody or 188Re-labeled non-specific IgM. Results: On Day 28 post-treatment the tumor size in the RIT group was 4-times less than in controls (P < 0.001). The tumors were analyzed by immunohistochemistry and FACS for two MSC markers — chemoresistance mediator ABCB5 and H3K4 demethylase JARID1B. There were no significant differences between RIT and control groups in percentage of ABCB5 or JARID1B-positive cells in the tumor population. Our results demonstrate that unlike chemotherapy, which kills tumor cells but leaves behind MSC leading to recurrence, RIT kills MSC at the same rate as the rest of tumor cells. Conclusions: These results have two main implications for melanoma treatment and possibly other cancers. First, the susceptibility of ABCB5 + and JARID1B + cells to RIT in melanoma might be indicative of their susceptibility to antibody-targeted radiation in other cancers where they are present as well. Second, specifically targeting cancer stem cells with radiolabeled antibodies to ABCB5 or JARID1B might help to completely eradicate cancer stem cells in various cancers

  9. Cancer epidemiology in developing countries

    International Nuclear Information System (INIS)

    It is estimated that there were over 10 million new cancer cases in 2000, 5.4 million of them occurring in the developing countries (Parkin et al, 2001). The marked geographical variation in cancer occurrence results in differing therapeutic priorities: North America has more new cancer cases than South-Central Asia, but there are more deaths from cancer in South-Central Asia, reflecting a different pattern of cancer rather than differences in prognosis. Prediction of future trends is difficult, but the impact of population increase and ageing will be significant, with an expected 63% increase in the population of the less developed countries in 50 years. Four sites of cancer namely breast, cervix, colorectal and nasopharyngeal carcinoma are reviewed, looking at their present and possible future importance in the context of developing countries and their aetiology

  10. Dosimetric measurements and radiobiological consequences of radioimmunotherapy in tumor bearing mice

    International Nuclear Information System (INIS)

    With the development of the hybridoma technology, the production of highly specific tumor associated monoclonal antibodies has provided new optimism for the adjuvant delivery of therapeutic radiation doses via radioimmunotherapy. The authors have used a modified form of the well-established TL dosimetry technology to measure the dose resulting from radioimmunotherapy experiments in tumor bearing mice. Their laboratory has designed and tested a miniature CaSO4:D TLD which fits conveniently inside a 20 gauge needle for the direct implantation of the dosimeter in an animal model undergoing radiolabeled antibody therapy. Direct measurement of absorbed dose from beta and gamma radiation in the animals may be obtained upon removal of the dosimeter at animal sacrifice or by surgery. This absorbed dose data may then be related to antibody affinity and localization data obtained by serial biodistribution studies. Using p96.5 melanoma antibody with a Brown Tumor Model in athymic mice, localization indices measured in the range of 2 to 4 and scored 4 to 7 days post antibody injection, yielded a tumor dose/whole body dose ratio of 1.10 +/- 0.04 (no enhancement). The dose to liver showed marker time-dependent enhancement relative to the whole body, however. An outline of suggested control radiobiological experiments to be performed in conjunction with radioimmunotherapy experiments has been included in order to provide comparative dose response data. 11 references, 14 figures, 3 tables

  11. Atopy and development of cancer

    DEFF Research Database (Denmark)

    Skaaby, Tea; Nystrup Husemoen, Lise Lotte; Roswall, Nina;

    2014-01-01

    BACKGROUND: Atopy is the familial or personal propensity to develop IgE antibodies against environmental allergens. Atopy, theoretically, could both prevent and promote the development of cancer. However, evidence from epidemiologic studies has been inconclusive. OBJECTIVE: We investigated the...

  12. Radioimmunotherapy for recurrent childhood hepatoblastoma after liver transplantation

    International Nuclear Information System (INIS)

    Full text: Monoclonal antibody has been developed for targeting secretory anti-fetoprotein in hepatic tissue. This antibody has been labelled with In-111 and Y-90 for clinical diagnostics and therapy, and can be applied for detecting hepatic neoplasms. Here, we use these antibodies for radiotherapy and radioimmunotherapy dose planning of hepatoblastoma, a rare childhood malignancy. Radiopharmacokinetic parameters were calculated after serial quantitative whole body scanning based on geometric mean images and transmission scanning. Biodistribution data and organ level kinetic parameters were calculated and were compared with those of nonclinical studies in mice. A 3-D dose planning programme was used to calculate tumor doses for In-111 and Y-90, the active tumor was delineated on PET/CT images and tumor dose calculation was done on In-111-MoAb SPECT data using dose point kernel approach both for In-111 and Y-90. The results were compared with MIRD doses obtained for organs in SPECT imaging field, i.e. bone marrow, heart, kidneys, liver, spleen, lungs. From quantitative serial imaging based on 8 whole body images at 0-168 hrs using In-111-anti-AFPMoAb, the half-lives of spleen, lungs, kidneys and whole body were 502 hrs, 230 hrs, 193 hrs and 490 hrs, respectively. The measured blood half-life was 132 hrs, after a total MoAb dose of 50 mg and In-111 activity of 105 MBq. The presumed Y-90 dose based on this kinetic behavior was 43 MBq which should had given 2 Gy bone marrow dose. The calculated MIRD Y-90 doses were for cardiac wall 0.75 Gy, liver 0.62 Gy, spleen 0.51Gy and bone marrow 0.053 Gy, and the effective whole body dose was 0.18 Gy, i.e. 4.23 mGy/MBq. The 3-D programme demonstrated the mean doses in normal tissues as follows: heart 0.58 Gy, liver 0.48 Gy, spleen 0.37 Gy and bone marrow 0.34 Gy. No toxicity was observed to the Y-90-anti- AFP radioimmunotherapy. The actual liver tumor dose according to the 3-D calculations was in average 0.51 Gy, range 0

  13. Chronic Inflammation in Cancer Development

    OpenAIRE

    Multhoff, Gabriele; Molls, Michael; Radons, Jürgen

    2012-01-01

    Chronic inflammatory mediators exert pleiotropic effects in the development of cancer. On the one hand, inflammation favors carcinogenesis, malignant transformation, tumor growth, invasion, and metastatic spread; on the other hand inflammation can stimulate immune effector mechanisms that might limit tumor growth. The link between cancer and inflammation depends on intrinsic and extrinsic pathways. Both pathways result in the activation of transcription factors such as NF-κB, STAT-3, and HIF-...

  14. Activities of AREVA Med. Extraction and purification of the 212Pb isotope from Thorium for radio-immunotherapy

    International Nuclear Information System (INIS)

    After having recalled the definition of radio-immunotherapy (RIT) and the benefits of alpha RIT for the treatment of some cancers, this document explains the choice of the 212-Pb isotope instead of the 212-Bi isotope (the first one has a longer half-life than the second). The Pb isotope in fact progressively transforms itself into the Bi isotope. The production process is evoked with its important steps. A second part reports the first clinic tests performed in the Alabama Centre for the treatment of different cancer (breast, colon, ovarian, pancreas, stomach). Processes and doses are discussed

  15. Dosimetrical considerations in astatine-211 radioimmunotherapy

    International Nuclear Information System (INIS)

    Several dosimetrical quantities have been suggested for use in alpha-particle dosimetry. To evaluate the expected biological effect when using these quantities, a Monte Carlo program was set to register the single-event distribution of both specific energy and alpha-particle track length to a cell nucleus (r=5.6 μm). Distributions were acquired for both 'bound' (simulating the effect of 211At-labelled antibodies bound to antigens on cell surfaces (r=7.0 μm)) as well as 'non-bound' (simulating 211At-labelled antibodies that have not bound to a cell) astatine-211. From these distributions, various theoretical cell survival curves were established for 3 different dosimetrical quantities, i.e. specific energy, number of alpha-particle hits and total track length. The survival curves for all quantities are presented for the corresponding mean absorbed dose in order to facilitate comparisons of the expected effects of using the 3 different quantities for both distributions of 211At decays. The theoretical survival curves presented here could, combined with experiments using 'bound' and 'non-bound' 211At in a single-cell suspension, reveal which dosimetrical quantity is most suitable for 211 At-radioimmunotherapy. (author)

  16. Pre-targeted radioimmunotherapy of solid tumors: A multidisciplinary approach; La radio-immunotherapie preciblee des tumeurs solides: une demarche pluridisciplinaire

    Energy Technology Data Exchange (ETDEWEB)

    Barbet, J.; Kraber-Bodere, F.; Faivre-Chauvet, A.; Gestin, J.F.; Bardies, M.; Chatal, J.F. [Institut National de la Sante et de la Recherche Medicale (INSERM), U601, Institut de Biologie, Dept. de Recherche en Cancerologie, 44 - Nantes (France); Nantes Univ., U601, Dept. de Recherche en Cancerologie, 44 (France); Campion, L. [Institut National de la Sante et de la Recherche Medicale (INSERM), U601, Institut de Biologie, Dept. de Recherche en Cancerologie, 44 - Nantes (France); Centre de lutte contre le cancer Rene-Gauducheau, 44 - Saint-Herblain (France)

    2007-09-15

    No effective therapy is currently available for the management of patients with metastases of most solid tumors. Thus, pre targeted radioimmunotherapy approaches have been developed that have shown promises. One of these techniques uses bi specific monoclonal antibody and radiolabeled bivalent haptens injected sequentially. In two clinical trials, 29 patients with advanced, progressive medullary thyroid carcinoma, as documented by short serum calcitonin doubling times, received an anti-carcinoembryonic antigen x anti-diethylenetriamine pentaacetic acid (DTPA)-indium) bi specific monoclonal antibody, followed four to five days later by an {sup 131}I-labeled bivalent hapten. Overall survival was significantly longer in high-risk, treated patients than in high-risk, untreated patients (110 versus 61 months; P < 0.030). Forty-seven percent of patients, defined as biologic responders by a more than 100% increase in calcitonin doubling time, experienced significantly longer survival than non-responders (159 versus 109 months; P < 0.035) and untreated patients (159 versus 61 months; P < 0.010). Toxicity was mainly hematologic and related to bone/bone-marrow tumor spread. Various multidisciplinary aspects of this long-term endeavor that resulted in long-term disease stabilization and a significantly longer survival in high-risk patients are described and discussed with respect to future directions of research on pre targeted radioimmunotherapy. (authors)

  17. Optimising the therapeutic ratio of radioimmunotherapy; an investigation of the roles of chimerisation, fractionation and radiation dosimetry

    Science.gov (United States)

    Violet, John Albert

    2007-12-01

    Radioimmunotherapy (RIT) is a targeted form of treatment for cancer which uses tumour-associated antibodies to selectively deliver a therapeutic radionuclide to sites of disease. In lymphoma, radioimmunotherapy has proved a remarkably effective agent due to the high radiosensitivity of the tumour and its propensity to undergo apoptosis following irradiation. However, success in the treatment of the more radioresistant common solid tumours has been less successful, and for these patients RIT remains investigative. The effectiveness of RIT is limited by non-specific irradiation of normal tissues whilst antibody remains in the circulation, in particular bone marrow, and also by immunogenicity of antibody which does not allow for repeated therapy. In the first chapter I have hypothesised that lymphomas expressing the interleukin-2 receptor might be effectively treated using a radiolabeled antibody to this receptor. In a phase I/II clinical study, 131I labelled CHT-25, a chimeric antibody against the IL-2Ra chain, has shown encouraging evidence of efficacy in the 9 patients with multiply- relapsed lymphomas treated so far. In addition, use of this antibody has been associated with low immunogenicity allowing for repeated therapies to be given. In the second chapter I have hypothesised that dosimetry led, individual patient therapy, might further optimise 1311 CHT-25 treatment. To investigate this I have used marrow toxicity as a biological assay of absorbed dose and shown that simple, but individual, patient biodistribution indices correlate better with observed toxicity than the population-based dose estimates currently employed. I have proposed that adoption of individual patient dosimetry using tracer studies is worthy of further investigation for the future development of 131I- CHT-25. In the third chapter I have hypothesised that dose fractionation might improve the therapeutic ratio of RIT. This has been investigated in a pre-clinical human colorectal xenograft

  18. Challenges for cancer vaccine development.

    Science.gov (United States)

    Tabi, Z; Man, S

    2006-10-01

    The first generation of human cancer vaccines has been tested in phase III clinical trials, but only a few of these have demonstrated sufficient efficacy to be licensed for clinical use. This article reviews some of the mechanisms that could contribute to these limited clinical responses, and highlights the challenges faced for development of future vaccines. PMID:16979786

  19. Preparation and quality control and biodistribution studies of [90Y]-DOTA-cetuximab for radioimmunotherapy

    International Nuclear Information System (INIS)

    Yttrium-90 is a useful radionuclide for radioimmunotherapy (RIT) and the anti-epidermal growth factor receptor (anti-EGFR) antibody cetuximab is clinicsally approved for the treatment of EGFR-expressing metastatic colorectal cancer and advanced head and neck cancer. Thus in this work radiolabeling of monoclonal anti-EGFR with 90Y for radioimmunotherapy (RIT) is targeted. Cetuximab was successively labeled with [90Y] chloride (74 MBq) 2 mCi after conjugation with macrocyclics bifunctional chelating agent, 1,4,7,10-tetraazacyclododecane-N,N',N',N'-tetraacetic acid mono-(N-hydroxysuccinimidyl) ester (DOTA-NHS), purified and concentrated by centrifugation using an Amicon Ultra-15 filter (Millipore, MWCo, 30000). 90Y chloride was obtained by 90Sr/90Y generator. Radiolabeling was completed in 2 h by the addition of DOTA-cetuximab conjugate at 42 °C. The stability of radiolabeled was studied in human serum. Biodistribution studies in normal rats were carried out to determine the radioimmunoconjugate distribution up to 96 h. Radiochemical purity of 92 % (using ITLC) was obtained for final radioimmunoconjugate (Specific activity = 0.55 GBq/mg). Stability of radiolabeled protein in presence of human serum was tested at 37 °C for up to 24 h. Biodistribution studies demonstrated the highest ID/g % in the blood (2.62 ± 0.005 at 24 h) and the liver (2.19 ± 0.001). This study demonstrated that 90Y-DOTA-cetuximab is a potential compound for the treatment of EGFR-expressing cancers. (author)

  20. Multi-step radioimmunotherapy of ovarian carcinomatosis

    International Nuclear Information System (INIS)

    Ovarian cancer is the leading cause of mortality among gynecological malignancies. Some 70 - 80% of patients fail conventional therapy, eventually succumbing to ovarian carcinomatosis. We are exploring a multi-step targeting approach as an adjuvant therapy to surgical debulking of the tumour. The prospective intraperitoneal treatment involves administration of a bispecific antibody to target CA-125 on the surface of ovarian cancer cells and biotin; followed by administration of biotinylated, radiolabeled liposomes to effect selective tumour cell killing within the peritoneal cavity. The goal of the study is to provide efficacious control of peritoneal metastatic disease, with improved quality and duration of the life of the patient. Bispecific antibodies to the human ovarian tumour-associated antigen, CA-125, were engineered and their selective targeting of human NIH:OVCAR-3 ovarian cancer cells was demonstrated by confocal laser scanning microscopy. Co-localisation of biotinylated, long-circulating liposomes was demonstrated, using the same technique. Kinetics analysis of internalisation and shedding of the antigen/antibody complex demonstrates an effective residency on the cell surface for at least four hours in vitro. Biodistribution studies in immunodeficient Balb/c mice demonstrate selective tumour association of radiolabeled, targeted liposomes. Tumour growth delay/control studies are imminently planned. Our current results warrant further development of this approach as a potential therapy for human ovarian carcinomatosis

  1. Update on the rational use of tositumomab and iodine-131 tositumomab radioimmunotherapy for the treatment of non-Hodgkin’s lymphoma

    OpenAIRE

    Burdick, Michael J; Macklis, Roger M.

    2009-01-01

    Michael J Burdick, Roger M MacklisDepartment of Radiation Oncology, Taussig Cancer Center and Cleveland Clinic Lerner College of Medicine, Cleveland, OH, USAAbstract: Targeted radioimmunotherapy in non-Hodgkin’s B-cell lymphoma (NHL) offers an efficacious therapy and minimal toxicity compared to conventional chemotherapy. Iodine 131 tositumomab (131I-TST) is a murine monoclonal antibody against the CD20 cell surface protein and is directly covalently conjugated to 131I, a radioactiv...

  2. Single-dose anti-CD138 radioimmunotherapy: bismuth-213 is more efficient than lutetium-177 for treatment of multiple myeloma in a preclinical model

    OpenAIRE

    Fichou, Nolwenn; Gouard, Sébastien; Maurel, Catherine; Barbet, Jacques; Ferrer, Ludovic; Morgenstern, Alfred; Bruchertseifer, Frank; Faivre-Chauvet, Alain; Bigot-Corbel, Edith; Davodeau, François; Gaschet, Joëlle; Chérel, Michel

    2015-01-01

    Objectives Radioimmunotherapy (RIT) has emerged as a potential treatment option for multiple myeloma (MM). In humans, a dosimetry study recently showed the relevance of RIT using an antibody targeting the CD138 antigen. The therapeutic efficacy of RIT using an anti-CD138 antibody coupled to 213Bi, an α-emitter, was also demonstrated in a preclinical MM model. Since then, RIT with β-emitters has shown efficacy in treating hematologic cancer. In this paper, we investigate the therapeutic eff...

  3. Guideline for radioimmunotherapy of CD20+ follicular B-cell non-Hodgkin's lymphoma

    International Nuclear Information System (INIS)

    This guideline is a prerequisite for the quality management in the treatment of non-Hodgkon-lymphomas in patients with relapsed or refractory follicular lymphoma after rituximab therapy and as consolidation therapy after first remission following CHOP like treatment using radioimmunotherapy. It is based on an interdisciplinary consensus and contains background information and definitions as well as specified indications and detailed contraindications of treatment. Essential topics are the requirements for institutions performing the therapy. For instance, presence of an expert for medical physics, intense cooperation with all colleagues committed to treatment of lymphomas, and a certificate of instruction in radiochemical labelling and quality control are required. Furthermore, it is specified which patient data have to be available prior to performance of therapy and how treatment has to be carried out technically. Here, quality control and documentation of labelling are of great importance. After treatment, clinical quality control is mandatory (work-up of therapy data and follow-up of patients). Essential elements of follow-up are specified in detail. The complete treatment inclusive after-care has to be realised in close cooperation with those colleagues (hemato-oncologists) who propose, in general, radioimmuno-therapy under consideration of the development of the disease. (orig.)

  4. Estimates of dose to intraperitoneal micrometastases from alpha and beta emitters in radioimmunotherapy

    International Nuclear Information System (INIS)

    Intraperitoneal metastases from ovarian and other gynecologic tumors are a significant source of treatment failure. In recent years, investigators have used radiolabeled monoclonal antibodies to treat this disease with encouraging results. We have developed a dose calculational technique which generates isodose distributions from intraperitoneally administered alpha and beta particle emitters. In this study we apply the calculations to tissue biopsy samples to determine the adequacy of dose to ovarian micrometastases. Tissue samples from staging biopsies at the time of surgical debulking are scanned to identify small metastases. The patient population studied comprised those with ovarian disease who based on clinical criteria would be considered good candidates for intraperitoneal radioimmunotherapy. The regions of interest (which include the tumor and surface of the peritoneum) are digitized and tumor volumes are contoured. Dose calculations based on the modeling of intraperitoneally administered antibodies radiolabeled with various isotopes is performed and the minimum dose to tumor and normal tissue is assessed. For example, with tumor uptake of 0.1% injected dose per gram of tissue, the surface tumor dose from alpha emitters is up to 45,000 rads. The dose falls to 6000 rads at approximately 40 microns from the peritoneal surface. The surface dose from 20 mCi 90Y administered in 1500 ml saline is up to 10,000 rads, and at a 2-mm depth, approximately 2000 rads. From our calculation dose distribution from radioimmunotherapy varies as a function of physical characteristics of the isotope, absorption of activity, and amount of disease being treated

  5. Update on the rational use of tositumomab and iodine-131 tositumomab radioimmunotherapy for the treatment of non-Hodgkin’s lymphoma

    Directory of Open Access Journals (Sweden)

    Michael J Burdick

    2009-08-01

    Full Text Available Michael J Burdick, Roger M MacklisDepartment of Radiation Oncology, Taussig Cancer Center and Cleveland Clinic Lerner College of Medicine, Cleveland, OH, USAAbstract: Targeted radioimmunotherapy in non-Hodgkin’s B-cell lymphoma (NHL offers an efficacious therapy and minimal toxicity compared to conventional chemotherapy. Iodine 131 tositumomab (131I-TST is a murine monoclonal antibody against the CD20 cell surface protein and is directly covalently conjugated to 131I, a radioactive β and γ emitter. While initially approved for use in relapsed, refractory, or transformed low grade B-cell NHL, investigational uses with promising results include autologous stem cell transplant, intermediate grade NHL, and the frontline management of indolent NHL. This review summarizes the 131I-TST literature on mechanism of action, treatment indications, treatment delivery, efficacy, investigational uses, and future prospects.Keywords: tositumomab, radioimmunotherapy, non-Hodgkin’s lymphoma, Bexxar

  6. A report of the medical technology assessment on radioimmunotherapy for B-cell non-Hodgkin lymphoma patients using yttrium-90 ibritumomab tiuxetan

    International Nuclear Information System (INIS)

    Radioimmunotherapy with unsealed source 90Y-ibritumomab tiuxetan requires physicians and paramedics who have adequate knowledge and experience as to anti-cancer chemotherapy, radiation therapy, handling of radioactive materials, etc. as well as adequate facilities, equipments and safety management system. The Japanese Society of Nuclear Medicine and the Japanese Society for Therapeutic Radiology and Oncology recently conducted an economic evaluation about radioimmunotherapy using 90Y-ibritumomab tiuxetan based on the medical technology assessment at the 16 medical facilities. As a result of this survey, the necessity to improve the current reimbursement system under national health insurance has been suggested, so that the cost (4450 ten for five times) for this therapy at the medical facility can be appropriately reimbursed for the proper dissemination of this therapy. (author)

  7. Radioimmunotherapy for lymphoma - analysis of clinical trials and treatment algorithms

    International Nuclear Information System (INIS)

    Ibritumomab, an 90Yttrium (90Y) labelled radioimmunoconjugate, is registered in Europe to treat follicular lymphomas. Its mode of action combines the selectivity of monoclonal antibodies with the efficiency of radiotherapy, making it a unique and useful therapeutic agent. This paper is for haemato-oncologists with a decent practice in lymphoma therapy, who have not yet used ibritumomab themselves. It summarizes clinical trials with radioimmunotherapy, indicating clinical situations where it may be specifically useful. (author)

  8. Study of in vivo generators Pb-212/Bi--212 and U-230/Th-226 for alpha radioimmunotherapy

    International Nuclear Information System (INIS)

    Alpha-radioimmunotherapy is a promising cancer therapy that uses a-particles vectorized by monoclonal antibody to break down cancerous tumors. The notion of in vivo generator was introduced in 1989 by Leonard Mausner. The concept involves labeling of various molecular carriers (antibodies, peptides, etc) with intermediate half-life generator parents, which after accumulation in the desired tissue generate much shorter half-life daughter radionuclide. This thesis focuses on the study of two in vivo generators potentially interesting for alpha-radioimmunotherapy: Pb-212 / Bi-212 generator and U-230 / Th-226 generator. The first part of this work presents the Pb-212 / Bi-212 generator, two approaches allowing the vectorization. Chelation approach on a protein and an approach by encapsulation in liposomes have been proposed. This last approach appears to be the most interesting. In vitro stability studies have been performed on these labeling. The second part of this work presents the U-230 / Th-226 generator. Studies have first been made to achieve a theoretical model to describe the speciation of Th(IV) in human serum. The efficacy of DTPA as chelating agent for complexation of Th(IV) in human serum could thus be estimated. (author)

  9. Developing cancer warning statements for alcoholic beverages

    OpenAIRE

    Pettigrew, Simone; Jongenelis, Michelle; Chikritzhs, Tanya; Slevin, Terry; Pratt, Iain S; Glance, David; Liang, Wenbin

    2014-01-01

    Background There is growing evidence of the increased cancer risk associated with alcohol consumption, but this is not well understood by the general public. This study investigated the acceptability among drinkers of cancer warning statements for alcoholic beverages. Methods Six focus groups were conducted with Australian drinkers to develop a series of cancer-related warning statements for alcohol products. Eleven cancer warning statements and one general health warning statement were subse...

  10. Progress and controversies in developing cancer vaccines

    Directory of Open Access Journals (Sweden)

    Speiser Daniel E

    2005-04-01

    Full Text Available Abstract Immunotherapy has become a standard approach for cancer management, through the use of cytokines (eg: interleukin-2 and monoclonal antibodies. Cancer vaccines hold promise as another form of immunotherapy, and there has been substantial progress in identifying shared antigens recognized by T cells, in developing vaccine approaches that induce antigen-specific T cell responses in cancer patients, and in developing new technology for monitoring immune responses in various human tissue compartments. Dramatic clinical regressions of human solid tumors have occurred with some cancer vaccines, but the rate of those responses remains low. This article is part of a 2-part point:counterpoint series on peptide vaccines and adoptive therapy approaches for cancer. The current status of cancer vaccination, and associated challenges, are discussed. Emphasis is placed on the need to increase our knowledge of cancer immunobiology, as well as to improve monitoring of cellular immune function after vaccination. Progress in both areas will facilitate development of effective cancer vaccines, as well as of adoptive therapy. Effective cancer vaccines promise to be useful for treatment and prevention of cancer at low cost and with low morbidity.

  11. Developing Effective Cancer Pain Education Programs

    OpenAIRE

    Martin, Michelle Y.; Pisu, Maria; Kvale, Elizabeth A.; Johns, Shelley A.

    2012-01-01

    Pain is prevalent, burdensome, and undertreated in individuals with cancer across the disease trajectory. Providing patients and family caregivers psychosocial support and education to manage cancer pain is a core component of quality care that can result in significant clinical benefit. In this review, we (1) outline an approach for developing and assessing the effectiveness of education programs for adults with cancer pain; (2) discuss considerations for tailoring programs to the needs of d...

  12. Areva: clinical trials for a new treatment to fight cancer; Areva: essais cliniques pour un nouveau traitement contre le cancer

    Energy Technology Data Exchange (ETDEWEB)

    Anon.

    2011-01-15

    Areva Med, the branch of Areva dedicated to nuclear medicine, has been agreed by the American Food and Drug Administration to begin the validation of a new treatment to fight cancer. This treatment is called alpha radio-immunotherapy and is based on the use of Pb{sup 212}. The validation phase aims at testing its efficiency on patients and will start in 2011 and will last 2 years. Areva has developed a process to extract Pb{sup 212} from thorium coming from ancient industrial activities. (A.C.)

  13. HOX Genes in Pancreatic Development and Cancer

    OpenAIRE

    Sophie Gray; Hardev S Pandha; Agnieszka Michael; Richard Morgan; Gary Middleton

    2011-01-01

    The HOX genes are a family of homeodomain-containing transcription factors that determine cellular identity during development and which are subsequently re-expressed in many types of cancer. Some recent studies have shown that HOX genes may have key roles both in pancreatic development and in adult diseases of the pancreas, including cancer. In this review we consider recent advances in elucidating the role of HOX genes in these processes, how they may connect early developmental events to s...

  14. CANCER NANOTECHNOLOGY: RECENT TRENDS AND DEVELOPMENTS

    Directory of Open Access Journals (Sweden)

    Mr. Hardik R Mody, B.Pharm

    2011-01-01

    Full Text Available Cancer is one of the leading causes of death worldwide. Deaths from cancer are continuously rising worldwide with a projection of about 12 million deaths from cancer in 2030. Hence, over the past few years, tremendous attention has been given to the cancer related research and there has been an outstanding progress in the basic cancer biology. The present article deals with the recent developments in cancer nanotechnologies and its potential application in cancer therapeutics. Nanotechnology is one of the most rapidly growing fields in the 21st century. It may be defined as the creation of materials, drugs and devices that are used to manipulate matter of size in the range of 1-100nm. Nanotechnology has found its applications in many fields related to medicine including novel drug delivery systems, biotechnology to name a few. Many different types of nanosystems have been utilized in diagnostics and therapeutics of various diseases. To subside the disadvantages of conventional cancer therapeutics, nanotechnology has been given considerable attention. In this paper, the current nanotechnologies that can be utilized in oncological interventions will be discussed. These mainly include arrays of nanocantilevers, nanotubes and nanowires for multiplexing detection, multifunctional injectable nanovectors for therapeutics and diagnostics.

  15. Colorectal cancer development and advances in screening

    OpenAIRE

    Simon K

    2016-01-01

    Karen Simon Ventura County Gastroenterology Medical Group, Inc., Camarillo, CA, USA Abstract: Most colon tumors develop via a multistep process involving a series of histological, morphological, and genetic changes that accumulate over time. This has allowed for screening and detection of early-stage precancerous polyps before they become cancerous in individuals at average risk for colorectal cancer (CRC), which may lead to substantial decreases in the incidence of CRC. Despite the known b...

  16. Criteria for the selection of radionuclides for tumor radioimmunotherapy

    International Nuclear Information System (INIS)

    The potential of utilizing monoclonal antibodies as carriers of radionuclides for the selective destruction of tumors (radioimmunotherapy, RIT) has stimulated much research activity. From dosimetric and other considerations, the choice of radiolabel is an important factor that needs to be optimized for maximum effectiveness of RIT. This paper reviews and assesses a number of present and future radionuclides that are particularly suitable for RIT based on the various physical, chemical, and biological considerations. Intermediate to high-energy beta emitters' (with and without gamma photons in their emission) are emphasized since they possess a number of advantages over alpha and Auger emitters. Factors relating to the production and availability of candidate radiometals as well as their stable chemical attachment to monoclonal antibodies are discussed. 34 refs., 4 tabs

  17. Development of New Treatments for Prostate Cancer

    Energy Technology Data Exchange (ETDEWEB)

    DiPaola, R. S.; Abate-Shen, C.; Hait, W. N.

    2005-02-01

    The Dean and Betty Gallo Prostate Cancer Center (GPCC) was established with the goal of eradicating prostate cancer and improving the lives of men at risk for the disease through research, treatment, education and prevention. GPCC was founded in the memory of Dean Gallo, a beloved New Jersey Congressman who died tragically of prostate cancer diagnosed at an advanced stage. GPCC unites a team of outstanding researchers and clinicians who are committed to high-quality basic research, translation of innovative research to the clinic, exceptional patient care, and improving public education and awareness of prostate cancer. GPCC is a center of excellence of The Cancer Institute of New Jersey, which is the only NCI-designated comprehensive cancer center in the state. GPCC efforts are now integrated well as part of our Prostate Program at CINJ, in which Dr. Robert DiPaola and Dr. Cory Abate-Shen are co-leaders. The Prostate Program unites 19 investigators from 10 academic departments who have broad and complementary expertise in prostate cancer research. The overall goal and unifying theme is to elucidate basic mechanisms of prostate growth and oncogenesis, with the ultimate goal of promoting new and effective strategies for the eradication of prostate cancer. Members' wide range of research interests collectively optimize the chances of providing new insights into normal prostate biology and unraveling the molecular pathophysiology of prostate cancer. Cell culture and powerful animal models developed by program members recapitulate the various stages of prostate cancer progression, including prostatic intraepithelial neoplasia, adenocarcinoma, androgen-independence, invasion and metastases. These models promise to further strengthen an already robust program of investigator-initiated therapeutic clinical trials, including studies adopted by national cooperative groups. Efforts to translate laboratory results into clinical studies of early detection and

  18. HOX Genes in Pancreatic Development and Cancer

    Directory of Open Access Journals (Sweden)

    Sophie Gray

    2011-05-01

    Full Text Available The HOX genes are a family of homeodomain-containing transcription factors that determine cellular identity during development and which are subsequently re-expressed in many types of cancer. Some recent studies have shown that HOX genes may have key roles both in pancreatic development and in adult diseases of the pancreas, including cancer. In this review we consider recent advances in elucidating the role of HOX genes in these processes, how they may connect early developmental events to subsequent adult disease, and their potential both as diagnostic markers and therapeutic targets.

  19. Anti-CD45 radioimmunotherapy using 211At with bone marrow transplantation prolongs survival in a disseminated murine leukemia model

    Energy Technology Data Exchange (ETDEWEB)

    Orozco, Johnnie J.; Back, Tom; Kenoyer, Aimee L.; Balkin, Ethan R.; Hamlin, Donald K.; Wilbur, D. Scott; Fisher, Darrell R.; Frayo, Shani; Hylarides, Mark; Green, Damian J.; Gopal, Ajay K.; Press, Oliver W.; Pagel, John M.

    2013-05-15

    Anti-CD45 Radioimmunotherapy using an Alpha-Emitting Radionuclide 211At Combined with Bone Marrow Transplantation Prolongs Survival in a Disseminated Murine Leukemia Model ABSTRACT Despite aggressive chemotherapy combined with hematopoietic cell transplant (HCT), many patients with acute myeloid leukemia (AML) relapse. Radioimmunotherapy (RIT) using antibodies (Ab) labeled primarily with beta-emitting radionuclides has been explored to reduce relapse.

  20. The role of neutering in cancer development.

    Science.gov (United States)

    Smith, Annette N

    2014-09-01

    Increased discussion on the influence of neutering on cancer development has been recently prompted with several studies that seem to indicate that incidence of some cancers may be increased with castration or spaying in our canine populations. Although the data are thought-provoking, we may not be able to extrapolate findings in single dog breeds to the entire species. Additionally, societal and humane issues related to pet overpopulation, as well as the incidence of other noncancerous diseases, behavior issues, and potentially decreased overall lifespan in unaltered animals must be taken into consideration before wholesale rejection of neutering in pets. PMID:25174910

  1. Development of cancer cooperative groups in Japan.

    Science.gov (United States)

    Fukuda, Haruhiko

    2010-09-01

    Investigator-initiated clinical trials are essential for improving the standard of care for cancer patients, because pharmaceutical companies do not conduct trials that evaluate combination chemotherapy using drugs from different companies, surgery, radiotherapy or multimodal treatments. Government-sponsored cooperative groups have played a vital role in developing cancer therapeutics since the 1950s in the USA; however, the establishment of these groups in Japan did not take place until 30 years later. Methodological standards for multicenter cancer clinical trials were established in the 1980s by the National Cancer Institute and cooperative groups. The Japan Clinical Oncology Group, one of the largest cooperative groups in the country, was instituted in 1990. Its data center and operations office, formed during the 1990s, applied the standard methods of US cooperative groups. At present, the Japan Clinical Oncology Group consists of 14 subgroups, a Data Center, an Operations Office, nine standing committees and an Executive Committee represented by the Japan Clinical Oncology Group Chair. Quality control and quality assurance at the Japan Clinical Oncology Group, including regular central monitoring, statistical methods, interim analyses, adverse event reporting and site visit audit, have complied with international standards. Other cooperative groups have also been established in Japan since the 1980s; however, nobody figures out all of them. A project involving the restructuring of US cooperative groups has been ongoing since 2005. Learning from the success of this project will permit further progress of the cancer clinical trials enterprise in Japan. PMID:20670961

  2. Cancer Drug Development: New Targets for Cancer Treatment.

    Science.gov (United States)

    Curt

    1996-01-01

    There is often a considerable lapse of time between the definition of what causes a disease in the laboratory and the development of successful therapy. However, the history of medicine teaches us that the need to understand the scientific basis of disease before the discovery of new treatments is both essential and inevitable. During the middle of the 19th century, the work of the great German pathologist, Rudolf Virchow, defined disease as having an anatomic or histologic basis. In the clinic, this scientific perspective would lead to increasingly effective and, often, increasingly aggressive surgical approaches to disease. Later in the 19th century, Koch's discovery of the tubercle bacillus (a discovery Virchow disbelieved and publication of which he thwarted, since he hypothesized that cancer, not microbes, caused consumption!), would define a microbiological basis for disease. With bacteria defined as a major cause of human suffering, the stage was set for the development of the discovery of effective antibiotics. In the early 20th century, the pioneering work of Banting, Best and others would show that disease can also have an endocrine or metabolic basis. This new body of scientific knowledge would lead not only to the specific discovery of insulin as an effective treatment for diabetes but also to a more general understanding of the role of hormones, vitamins and co-factors in human health and disease. Basic medical research and its successful translation into effective treatments has fundamentally altered the cause of human death. In the developed world, where access to the benefit of this work is available, infectious disease is not the problem it was in the days of Pasteur, Metchnikoff and Ehrlich. As we approach the millennium, science is now teaching us that diseases, particularly cancer, can have a molecular or genetic basis. Can successful application of this new knowledge be far behind? We are already seeing the application of this new knowledge in

  3. DNA damage checkpoint recovery and cancer development

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Haiyong [First affiliated hospital, Zhejiang University, School of medicine, Cancer Center, 79 Qingchun Road, Hangzhou 310003 (China); Zhang, Xiaoshan [Department of Genetics, University of Texas M.D. Anderson Cancer Center, Department of Genetics Unit 1010, 1515 Holcombe Blvd. Houston, TX 77030 (United States); Teng, Lisong, E-mail: lsteng@zju.edu.cn [First affiliated hospital, Zhejiang University, School of medicine, Cancer Center, 79 Qingchun Road, Hangzhou 310003 (China); Legerski, Randy J., E-mail: rlegersk@mdanderson.org [Department of Genetics, University of Texas M.D. Anderson Cancer Center, Department of Genetics Unit 1010, 1515 Holcombe Blvd. Houston, TX 77030 (United States)

    2015-06-10

    Cell cycle checkpoints were initially presumed to function as a regulator of cell cycle machinery in response to different genotoxic stresses, and later found to play an important role in the process of tumorigenesis by acting as a guard against DNA over-replication. As a counterpart of checkpoint activation, the checkpoint recovery machinery is working in opposition, aiming to reverse the checkpoint activation and resume the normal cell cycle. The DNA damage response (DDR) and oncogene induced senescence (OIS) are frequently found in precancerous lesions, and believed to constitute a barrier to tumorigenesis, however, the DDR and OIS have been observed to be diminished in advanced cancers of most tissue origins. These findings suggest that when progressing from pre-neoplastic lesions to cancer, DNA damage checkpoint barriers are overridden. How the DDR checkpoint is bypassed in this process remains largely unknown. Activated cytokine and growth factor-signaling pathways were very recently shown to suppress the DDR and to promote uncontrolled cell proliferation in the context of oncovirus infection. In recent decades, data from cell line and tumor models showed that a group of checkpoint recovery proteins function in promoting tumor progression; data from patient samples also showed overexpression of checkpoint recovery proteins in human cancer tissues and a correlation with patients' poor prognosis. In this review, the known cell cycle checkpoint recovery proteins and their roles in DNA damage checkpoint recovery are reviewed, as well as their implications in cancer development. This review also provides insight into the mechanism by which the DDR suppresses oncogene-driven tumorigenesis and tumor progression. - Highlights: • DNA damage checkpoint works as a barrier to cancer initiation. • DDR machinary response to genotoxic and oncogenic stress in similar way. • Checkpoint recovery pathways provide active signaling in cell cycle control. • Checkpoint

  4. DNA damage checkpoint recovery and cancer development

    International Nuclear Information System (INIS)

    Cell cycle checkpoints were initially presumed to function as a regulator of cell cycle machinery in response to different genotoxic stresses, and later found to play an important role in the process of tumorigenesis by acting as a guard against DNA over-replication. As a counterpart of checkpoint activation, the checkpoint recovery machinery is working in opposition, aiming to reverse the checkpoint activation and resume the normal cell cycle. The DNA damage response (DDR) and oncogene induced senescence (OIS) are frequently found in precancerous lesions, and believed to constitute a barrier to tumorigenesis, however, the DDR and OIS have been observed to be diminished in advanced cancers of most tissue origins. These findings suggest that when progressing from pre-neoplastic lesions to cancer, DNA damage checkpoint barriers are overridden. How the DDR checkpoint is bypassed in this process remains largely unknown. Activated cytokine and growth factor-signaling pathways were very recently shown to suppress the DDR and to promote uncontrolled cell proliferation in the context of oncovirus infection. In recent decades, data from cell line and tumor models showed that a group of checkpoint recovery proteins function in promoting tumor progression; data from patient samples also showed overexpression of checkpoint recovery proteins in human cancer tissues and a correlation with patients' poor prognosis. In this review, the known cell cycle checkpoint recovery proteins and their roles in DNA damage checkpoint recovery are reviewed, as well as their implications in cancer development. This review also provides insight into the mechanism by which the DDR suppresses oncogene-driven tumorigenesis and tumor progression. - Highlights: • DNA damage checkpoint works as a barrier to cancer initiation. • DDR machinary response to genotoxic and oncogenic stress in similar way. • Checkpoint recovery pathways provide active signaling in cell cycle control. • Checkpoint

  5. BK polyomavirus association with colorectal cancer development.

    Science.gov (United States)

    Khabaz, M N; Nedjadi, T; Gari, M A; Al-Maghrabi, J A; Atta, H M; Basuni, A A; Elderwi, D A

    2016-01-01

    The development of human neoplasms can be provoked by exposure to one of several viruses. Burkitt lymphoma, cervical carcinoma, and hepatocellular carcinoma are associated with Epstein-Barr, human papilloma, and hepatitis B virus infections, respectively. Over the past three decades, many studies have attempted to establish an association between colorectal cancer and viruses, with debatable results. The aim of the present research was to assess the presence of BK polyomavirus (BKV) DNA and protein in colorectal cancer samples from patients in the Western Province of Saudi Arabia. DNA extracted from archival samples of colorectal cancer tissues was analyzed for BKV sequences using polymerase chain reaction (PCR)-based techniques. In addition, expression of a BKV protein was assessed using immunohistochemical staining. None of the tumor and control samples examined tested positive for BKV DNA in PCR assays. Furthermore, immunohistochemical staining failed to detect viral proteins in both cancer and control specimens. These results may indicate that BKV is not associated with the development of colorectal adenocarcinoma in patients in the Western Province of Saudi Arabia. PMID:27173319

  6. Dosimetric considerations in radioimmunotherapy of patients with hepatoma

    International Nuclear Information System (INIS)

    Dosimetric studies of I-131 labeled antiferritin have provided the foundation for preparative and administrative aspects of radiolabeled antibody treatment of patients with hepatoma. Tumor response to I-131 labeled antiferritin IgG was encouraging and radioimmunotherapy with Y-90 labeled antiferritin IgG was recently initiated. For these patients, In-111 labeled antiferritin IgG was used as the imaging agent, with administered activities ranging from 0.8 - 7 mCi. Serial gamma camera imaging from 30 minutes to 6 days post injection demonstrated that 5-30% of the administered activity localized in hepatomas (8/12 patients). The mean value of the effective half-life in the tumor and liver was 2.8 d. Disappearance curves for the blood circulation, spleen, and other normal tissues were biphasic such that 50% of the activity disappeared within 24 hours post injection. The eight patients who demonstrated sufficient tumor localization where subsequently treated with Y-90 labeled antiferritin IgG. Administered activities were dependent on tumor volume and uptake of radiolabeled IgG and ranged from 8 - 20 mCi. The remaining patients were treated under other existing protocols. 10 references

  7. Radioimmunotherapy with Zevalin in Patients with Non-Hodgkin's Lymphoma

    International Nuclear Information System (INIS)

    Full text: The aim of this prospective study was to asses the value of new radioimmunotherapy treatment with Zevalin (IgG1 monoclonal antibody covalently bound to tiuxetan and labeled with Y-90) for adult patients with refractory or relapsed CD20+ follicular B-cell non- Hodgkin's lymphoma (NHL). This multicentric study included eight patients (median age 55 years, range 51-59 years) from five hospitals in Croatia. The treatment involved a day 1 infusion of rituximab 250 mg /m2; a second infusion of rituximab on day 8, followed by 'slow push' 10 minute infusion of Zevalin (median dose 1020 MBq; range 820- 1177 MBq). On follow-up 12 weeks after treatment response was achieved in six patients (75%). In three patients tumor mass was completely disappeared (complete response), and in other three patients tumor mass was significantly decreased (partial response). Hematological toxicity was observed in three patients and manifested with infections requiring hospitalization. One patient died because of extreme pancytopenia and Candida sepsis, in spite of support with granulocyte colony-stimulating factor. The median time to lowest blood counts was four weeks after Zevalin injection. Acute and non-hematological side effects were not observed. Our preliminary results confirmed Zevalin as a very effective therapy for patients with refractory or relapsed CD20+ follicular B-cell NHL. One should be aware of hematologic toxicity; therefore the close follow-up is required. (author)

  8. Importance of pre-treatment radiation absorbed dose estimation for radioimmunotherapy of non-Hodgkin's lymphoma

    International Nuclear Information System (INIS)

    Non-Hodgkin's lymphoma I-131 radioimmunotherapy data were analyzed to determine whether a predictive relationship exists between radiation absorbed doses calculated from biodistribution studies and doses derived from patient size. Radioactivity treatment administrations scaled to patient size (MBq/kg or MBq/m2) or fixed MBq doses do not produce consistent radiation absorbed dose to critical organs. Treatment trials that do not provide dose estimates for critical normal organs are less likely to succeed in identifying a clinical role for radioimmunotherapy

  9. Clinical Assay Development Support - Office of Cancer Clinical Proteomics Research

    Science.gov (United States)

    The NCI’s Division of Cancer Treatment and Diagnosis and the Cancer Diagnosis Program announce a request for applications for the Clinical Assay Development Program (CADP) for investigators seeking clinical assay development and validation resources.

  10. Avidin chase can reduce myelotoxicity associated with radioimmunotherapy of experimental liver micrometastases in mice

    International Nuclear Information System (INIS)

    Myelotoxicity is the main factor which decides the maximum tolerated dose (MTD) in radioimmunotherapy (RIT). Since bone marrow is mostly irradiated from blood radioactivity, enhancing the clearance of unbound circulating radiolabeled antibody is important to reduce myelotoxicity and to increase the MTD. We applied the avidin chase method, which was devised to obtain high tumor-to-background ratios in tumor-targeting, to RIT of experimental liver micrometastases and evaluated its influence on the side effects and therapeutic outcome. Seven days after intrasplenic injection of human colon cancer LS174T cells, nude mice were intravenously injected with biotinylated 131I-labeled anti-CEA monoclonal antibody (MAb) (24-38 μg, 11.1 MBq). Mice of the chase group then received an intravenous injection of avidin twice (24 and 30 h, 72-115 μg each). Biodistribution, side effects (white blood cell counts and body weight change), and short- and long-term therapeutic effects were determined. Avidin chase markedly accelerated the clearance of radiolabeled MAb from the blood (P<0.0001) and normal tissues, resulting in milder leukocytopenia and body weight loss, both of which recovered earlier than in the non-chase group (P<0.01). The tumor uptake of radiolabeled MAb was also decreased by avidin chase, but the metastases-to-background ratios were increased. Avidin chase gave the therapeutic gain ratio of 1.89. Treated groups with and without avidin chase showed significant therapeutic effects compared to the non-treated group. There was no significant difference in the therapeutic effects between the two treated groups. Avidin chase effectively reduced the side effects of RIT and should increase the MTD. (author)

  11. Antiangiogenic gene therapy of cancer: recent developments

    OpenAIRE

    Libutti Steven K; Blazer Dan G; Tandle Anita

    2004-01-01

    Abstract With the role of angiogenesis in tumor growth and progression firmly established, considerable effort has been directed to antiangiogenic therapy as a new modality to treat human cancers. Antiangiogenic agents have recently received much widespread attention but strategies for their optimal use are still being developed. Gene therapy represents an attractive alternative to recombinant protein administration for several reasons. This review evaluates the potential advantages of gene t...

  12. Two-compartment model of radioimmunotherapy delivered through cerebrospinal fluid

    Energy Technology Data Exchange (ETDEWEB)

    He, Ping [Johns Hopkins University, Department of Biomedical Engineering, Baltimore, MD (United States); Kramer, Kim; Cheung, Nai-Kong V. [Memorial Sloan-Kettering Cancer Center, Department of Pediatrics, New York, NY (United States); Smith-Jones, Peter; Larson, Steven M. [Memorial Sloan-Kettering Cancer Center, Department of Radiology, New York, NY (United States); Zanzonico, Pat; Humm, John [Memorial Sloan-Kettering Cancer Center, Department of Medical Physics, New York, NY (United States)

    2011-02-15

    Radioimmunotherapy (RIT) using {sup 131}I-3F8 injected into cerebrospinal fluid (CSF) was a safe modality for the treatment of leptomeningeal metastases (JCO, 25:5465, 2007). A single-compartment pharmacokinetic model described previously (JNM 50:1324, 2009) showed good fitting to the CSF radioactivity data obtained from patients. We now describe a two-compartment model to account for the ventricular reservoir of {sup 131}I-3F8 and to identify limiting factors that may impact therapeutic ratio. Each parameter was examined for its effects on (1) the area under the radioactivity concentration curve of the bound antibody (AUC[C{sub IAR}]), (2) that of the unbound antibody AUC[C{sub IA}], and (3) their therapeutic ratio (AUC[C{sub IAR}]/AUC[C{sub IA}]). Data fitting showed that CSF kBq/ml data fitted well using the two-compartment model (R = 0.95 {+-} 0.03). Correlations were substantially better when compared to the one-compartment model (R = 0.92 {+-} 0.11 versus 0.77 {+-} 0.21, p = 0.005). In addition, we made the following new predictions: (1) Increasing immunoreactivity of {sup 131}I-3F8 from 10% to 90% increased both (AUC[C{sub IAR}]) and therapeutic ratio (AUC[C{sub IAR}]/AUC[C{sub IA}]) by 7.4 fold, (2) When extrapolated to the clinical setting, the model predicted that if {sup 131}I-3F8 could be split into 4 doses of 1.4 mg each and given at {>=}24 hours apart, an antibody affinity of K{sub D} of 4 x 10{sup -9} at 50% immunoreactivity were adequate in order to deliver {>=}100 Gy to tumor cells while keeping normal CSF exposure to <10 Gy. This model predicted that immunoreactivity, affinity and optimal scheduling of antibody injections were crucial in improving therapeutic index. (orig.)

  13. External beam and radioimmunotherapy dosimetry comparison of colorectal xenografts

    International Nuclear Information System (INIS)

    It is of little surprise to most experts in radiation dosimetry that the largest uncertainties associated with calculation of absorbed doses to tumor normal tissues after IV administration of radiolabeled antibodies, does not lie in the calculation methods but rather in the acquisition of time-dependent activity data. In comparison to external beam radiation dosimetry, the problems of temporal and spatial macroscopic and microscopic heterogeneities continue to confound one's best efforts. In fact in some clinical settings, only a radiobiological end-point such as hematopoietic depression is used exclusively with no reference made to absorbed dose quantitation at all. Hence in these cases, it is most practical to simply relate administered activity directly with radiobiological response. To help provide a correlation between activity, absorbed dose and radiobiological response, animal radioimmunotherapy (RIT) experiments were performed here in which the above parameters were measured and compared with multiple dose levels of external beam irradiation. Using the LS174T colorectal xenograft model in nude mice, administered activities of up to 18.5 MBq of I-131 labeled B72.3 delivered an average measured absorbed dose to tumor of 3.2 ± 0.5 cGy/3.7 x 104 Bq. This absorbed dose (1,440 cGy from a nominal 17 MBq administered activity) produced tumor growth delay values that were comparable to a dose of 2,250 cGy on average delivered by single fraction external beam radiation therapy. An average dose enhancement ratio was calculated at 1.6 for RIT as compared with external beam therapy. This enhancement ratio ranged from 1.0-2.4 for several experimental repetitions under a variety of initial conditions

  14. Strategies to improve the efficacy of radioimmunotherapy: Radiobiologic aspects

    International Nuclear Information System (INIS)

    The purpose of this study was to investigate methods of improving the therapeutic index (dose to tumor/dose to normal organs) and, hence, the efficacy of radioimmunotherapy (RIT). One method investigated was to increase the biologic response for a given radiation dose to tumor. To enhance the biologic efficacy of the dose, initial studies focused on first understanding the radiobiology of RIT irradiation and determining what role factors, such as radiation repair, repopulation, and redistribution, play in determining RIT response. In vitro studies using 4 colon carcinoma cell lines have compared the radiobiologic efficacy of low dose-rate irradiation delivered by Yttrium-90 (Y-90) with conventional high dose-rate external beam irradiation (XRT). Results suggested that one factor which determined a cell's sensitivity to Y-90 irradiation was its ability to repair radiation sublethal damage. In vivo studies demonstrated that those cell lines which were more sensitive to Y-90 irradiation in vitro were also more sensitive to RIT in vivo. For a more radioresistant line, WiDr, RIT was approximately two-fold less effective than an equivalent dose of single fraction XRT, while for a more radiosensitive line, LS174T, RIT was approximately as effective as an equivalent dose of single fraction XRT. Therefore, a tumor's response to RIT in vivo appeared to be, in part, dependent on the tumor cell's ability to repair radiation damage. Finally, studies investigated strategies at enhancing the biologic efficacy of RIT irradiation by combining RIT with chemotherapy agents that can potentially inhibit radiation repair. Agents, such as 5-fluorouracil, appeared to be synergistic with RIT irradiation n vitro and may therefore prove promising in improving the therapeutic index of RIT

  15. The alpha immunotherapy - A successful solution in cancer treatment

    International Nuclear Information System (INIS)

    Full text: Radiation has been used in cancer therapy for many years. While, in the past the treatment involved mainly use of relatively low energy beta-emitters, more recently it was shown that isotopes emitting alpha particles have been more effective and selective against blood-borne cancers, widespread tumors and residual cells remaining after surgical intervention. This study shows that radioimmunotherapy (RIT) with α emitters may be therapeutically more effective than RIT with conventional β emitters. In the process of designing and developing the radioimmunotherapy procedures, the selection of the isotope is a major factor. This selection depends on a number of criteria and parameters, affecting usefulness and feasibility. Usefulness is directly related to the radiological performance of the ionising radiation in relation to tissue and its morphology, with a major distinction between the effects of alpha and beta-particles. Usefulness is also related to the pharmacodynamic performance of the isotope-carrier (e.g. antibody) complex, where the proper choice of isotope radiodecay half-life is essential. Feasibility depends on availability of the components in the isotope-ligand-carrier complex, and also on convenience and safety aspects in the preparation and the handling of the materials as well as in their application in patients. Alpha immunotherapy is based on emission of alpha particles by radionuclides. Due to its short physical t1/2, 213Bi appears to be especially suitable for use in conjunction with fast-clearing fragments; its 440-keV α emission also can be used for quantitation by external scintigraphy. Bismuth-213, a short-lived alpha particle emitting radionuclide, is generated from the decay of 225Ac, which has a half-life of 10 days. The development of a clinical 225Ac/213Bi generator and the preparation of a 213Bi radiolabeled antibody for radioimmunotherapy of leukemia is reported. Alpha emitting radionuclides are amongst the most promising

  16. Ovarian Cancer Stroma: Pathophysiology and the Roles in Cancer Development

    International Nuclear Information System (INIS)

    Ovarian cancer represents one of the cancers with the worst prognostic in adult women. More than half of the patients who present with clinical signs such as abdominal bloating and a feeling of fullness already show advanced stages. The majority of ovarian cancers grow as cystic masses, and cancer cells easily spread into the pelvic cavity once the cysts rupture or leak. When the ovarian cancer cells disseminate into the peritoneal cavity, metastatic nests may grow in the cul-de-sac, and in more advanced stages, the peritoneal surfaces of the upper abdomen become the next largest soil for cancer progression. Ascites is also produced frequently in ovarian cancers, which facilitates distant metastasis. Clinicopathologic, epidemiologic and molecular studies on ovarian cancers have improved our understanding and therapeutic approaches, but still further efforts are required to reduce the risks in the patients who are predisposed to this lethal disease and the mortality of the patients in advanced stages. Among various molecules involved in ovarian carcinogenesis, special genes such as TP53, BRCA1 and BRCA2 have been well investigated. These genes are widely accepted as the predisposing factors that trigger malignant transformation of the epithelial cells of the ovary. In addition, adnexal inflammatory conditions such as chronic salpingitis and ovarian endometriosis have been great research interests in the context of carcinogenic background of ovarian cancers. In this review, I discuss the roles of stromal cells and inflammatory factors in the carcinogenesis and progression of ovarian cancers

  17. Ovarian Cancer Stroma: Pathophysiology and the Roles in Cancer Development

    Energy Technology Data Exchange (ETDEWEB)

    Furuya, Mitsuko [Department of Pathology, Yokohama City University Graduate School of Medicine, Yokohama 236-0004 (Japan)

    2012-07-18

    Ovarian cancer represents one of the cancers with the worst prognostic in adult women. More than half of the patients who present with clinical signs such as abdominal bloating and a feeling of fullness already show advanced stages. The majority of ovarian cancers grow as cystic masses, and cancer cells easily spread into the pelvic cavity once the cysts rupture or leak. When the ovarian cancer cells disseminate into the peritoneal cavity, metastatic nests may grow in the cul-de-sac, and in more advanced stages, the peritoneal surfaces of the upper abdomen become the next largest soil for cancer progression. Ascites is also produced frequently in ovarian cancers, which facilitates distant metastasis. Clinicopathologic, epidemiologic and molecular studies on ovarian cancers have improved our understanding and therapeutic approaches, but still further efforts are required to reduce the risks in the patients who are predisposed to this lethal disease and the mortality of the patients in advanced stages. Among various molecules involved in ovarian carcinogenesis, special genes such as TP53, BRCA1 and BRCA2 have been well investigated. These genes are widely accepted as the predisposing factors that trigger malignant transformation of the epithelial cells of the ovary. In addition, adnexal inflammatory conditions such as chronic salpingitis and ovarian endometriosis have been great research interests in the context of carcinogenic background of ovarian cancers. In this review, I discuss the roles of stromal cells and inflammatory factors in the carcinogenesis and progression of ovarian cancers.

  18. Gene Expression Profiling Predicts the Development of Oral Cancer

    OpenAIRE

    Saintigny, Pierre; Zhang, Li; Fan, You-Hong; El-Naggar, Adel K.; Papadimitrakopoulou, Vali; Feng, Lei; Lee, J. Jack; Kim, Edward S.; Hong, Waun Ki; Mao, Li

    2011-01-01

    Patients with oral preneoplastic lesion (OPL) have high risk of developing oral cancer. Although certain risk factors such as smoking status and histology are known, our ability to predict oral cancer risk remains poor. The study objective was to determine the value of gene expression profiling in predicting oral cancer development. Gene expression profile was measured in 86 of 162 OPL patients who were enrolled in a clinical chemoprevention trial that used the incidence of oral cancer develo...

  19. Standard Operating Procedure for In-house Preparation of 131I-rituximab for Radioimmunotherapy of Non-Hodgkin's Lymphoma

    OpenAIRE

    Pickford, Matthew D.; Turner, J. Harvey

    2012-01-01

    A Standard Operating Procedure (SOP) has been formulated for in-house preparation, quality control, dispensing and administration of 131I-rituximab appropriate for the safe, effective, radioimmunotherapy of non-Hodgkin lymphoma. A decade of experience of semi-automated radioiodination of rituximab in our hospital radiopharmaceutical laboratory was analysed. The methodology was then refined for safe, practical, affordable application to radioimmunotherapy of lymphoma in departments of nuclear ...

  20. Translational Research in Pancreatic Cancer

    Directory of Open Access Journals (Sweden)

    Alexios S Strimpakos

    2011-03-01

    Full Text Available The high mortality rate of pancreatic cancer places this uncommon malignancy quite high as a cause of cancer related deaths. Compared to other solid tumors, there is a lag in the development of new effective drugs and the actual clinical benefit remains poor over the last decade or so. The lack of therapeutic options necessitates the invention of the important molecules playing role in pancreatic carcinogenesis and the development of specific targeted therapies. Treatment advances have to be proven first in the bench before applying them at the bedside, thus why translational research is so needed. At the 2011 American Society of Clinical Oncology (ASCO Gastrointestinal Cancers Symposium, preclinical evidence was presented regarding the efficacy of C4 compound against focal adhesion kinase (FAK (Abstract #214, the role of the cyclooxygenase-2 (COX-2 inhibitor apricoxib in enhancing the efficacy of gemcitabine and erlotinib (Abstract #227 and the role of curcumin and ABT-888 (a poly-ADP ribose polymerase (PARP inhibitor as potent radiosensitizers (Abstracts #222 and #203. Interestingly, the invention of a novel monoclonal antibody (ensituximab against the mucin epitope NPC-1C in pancreatic and colon cancer cell lines exhibited notable antibody-dependent cellular cytotoxicity (Abstract #235. Finally, enhanced selective targeting of pancreatic tumors was achieved by combining antibody-drug conjugates (ADC with radioimmunotherapy (Abstract #206.

  1. Radionuclide imaging and treatment of thyroid cancer.

    Science.gov (United States)

    Wang, Xiu Juan; Li, XianFeng; Ren, Yuan

    2016-01-01

    Over the past decades, the diagnostic methods and therapeutic tools for thyroid cancer (TC) have been greatly improved. In addition to the classical method of ingestion of radioactive iodine-131 (I131) and subsequent I123 and I124 positron emission tomography (PET) in therapy and examination, I124 PET-based 3-dimensional imaging, Ga68-labeled [1, 4, 7, 10-tetraazacyclododecane-1, 4, 7, 10-tetraacetic acid]-1-NaI(3)-octreotide (DOTANOC) PET/computed tomography (CT), Tc99m tetrofosmin, pre-targeted radioimmunotherapy, and peptide receptor radionuclide therapy have all been used clinically. These novel methods are useful in diagnosis and therapy of TC, but also have unavoidable adverse effects. In this review, we will discuss the development of nuclear medicine in TC examination and treatment. PMID:27100499

  2. Processed pseudogenes acquired somatically during cancer development

    OpenAIRE

    Cooke, Susanna L.; Shlien, Adam; Marshall, John; Pipinikas, Christodoulos P; Martincorena, Inigo; Tubio, Jose M. C.; Li, Yilong; Menzies, Andrew; Mudie, Laura; Ramakrishna, Manasa; Yates, Lucy; Davies, Helen; Bolli, Niccolo; Bignell, Graham R; Tarpey, Patrick S.

    2014-01-01

    Cancer evolves by mutation, with somatic reactivation of retrotransposons being one such mutational process. Germline retrotransposition can cause processed pseudogenes, but whether this occurs somatically has not been evaluated. Here we screen sequencing data from 660 cancer samples for somatically acquired pseudogenes. We find 42 events in 17 samples, especially non-small cell lung cancer (5/27) and colorectal cancer (2/11). Genomic features mirror those of germline LINE element retrotransp...

  3. Radioimmunotherapy for pancreatic carcinoma using 131I-labeled monoclonal antibody Nd2 in xenografted nude mice

    International Nuclear Information System (INIS)

    We investigated the biodistribution, radiolocalization, and radioimmunotherapeutic potential of 131I-labeled Nd2 in athymic nude mice bearing human pancreatic carcinoma xenografts. 131I-Nd2 was accumulated at high levels in the tumor, in contrast to blood, liver, spleen, and other normal organs. The tumor was clearly delineated in scintigraphs. The volumes of tumors of mice injected with 7.4 MBq of 131I-Nd2 were 80% less than those of tumors before injection of radiolabeled Nd2. Fibrous or vacuolar degeneration was seen in histological sections of tumors of 7-week-treated mice. The growth of tumors in mice treated with misonidazole, a hypoxic cell radiosensitizer, and then injected twice with 3.7 MBq of 131I-Nd2 was suppressed over 7 weeks. Neither leucocytopenia nor thrombocytopenia was severe after injection of radiolabeled Nd2. Thus 131I-labeled Nd2 may have clinical application in the radioimmunotherapy of pancreatic cancer. (author)

  4. Guideline for radioimmunotherapy of rituximab relapsed or refractory CD20{sup +} follicular B-cell non-Hodgkin's lymphoma

    Energy Technology Data Exchange (ETDEWEB)

    Fischer, M.; Behr, T.; Gruenwald, F.; Knapp, W.H. [Deutsche Gesellschaft fuer Nuklearmedizin (DGN) (Germany); Truemper, L.; Schilling, C. von [Deutsche Gesellschaft fuer Haematologie und Onkologie e.V., Muenchen (Germany)

    2004-10-01

    This guideline is a prerequisite for the quality management in the treatment of non-Hodgkin-lymphomas using radioimmunotherapy. It is based on an interdisciplinary consensus and contains background information and definitions as well as specified indications and detailed contraindications of treatment. Essential topics are the requirements for institutions performing the therapy. For instance, presence of an expert for medical physics, intense cooperation with all colleagues committed to treatment of lymphomas, and a certificate of instruction in radiochemical labelling and quality control are required. Furthermore, it is specified which patient data have to be available prior to performance of therapy and how the treatment has to be carried out technically. Here, quality control and documentation of labelling are of greatest importance. After treatment, clinical quality control is mandatory (work-up of therapy data and follow-up of patients). Essential elements of follow-up are specified in detail. The complete treatment inclusive after-care has to be realised in close cooperation with those colleagues (haematology-oncology) who propose, in general, radioimmunotherapy under consideration of the development of the disease. (orig.)

  5. Recent developments and innovations in gastric cancer

    OpenAIRE

    Mihmanli, Mehmet; Ilhan, Enver; Idiz, Ufuk Oguz; ALEMDAR, Ali; Demir, Uygar

    2016-01-01

    Gastric cancer has an important place in the worldwide incidence of cancer and cancer-related deaths. It can metastasize to the lymph nodes in the early stages, and lymph node metastasis is an important prognostic factor. Surgery is a very important part of gastric cancer treatment. A D2 lymphadenectomy is the standard surgical treatment for cT1N+ and T2-T4 cancers, which are potentially curable. Recently, the TNM classification system was reorganized, and the margins for gastrectomy and lymp...

  6. Oral cancer in Libya and development of regional oral cancer registries: A review

    OpenAIRE

    BenNasir, E.; El Mistiri, M.; Mcgowan, R.; Katz, R.V.

    2015-01-01

    The aims of this paper are three-fold: (1) to summarize the current epidemiological data on oral cancer in Libya as reported in the published literature and as compared to other national oral cancer rates in the region; (2) to present both the history of the early development, and future goals, of population-based oral cancer tumor registries in Libya as they partner with the more established regional and international population-based cancer tumor registries; and, (3) to offer recommendation...

  7. I-131 rituximab (chimeric anti Cd 20 mab) radioimmunotherapy of non-Hodgkins lymphoma

    International Nuclear Information System (INIS)

    Full text: Commercially available anti-CD 20 monoclonal antibody, rituximab (MabThera) may be efficiently radioiodinated with 131I using standard Chloramine-T methodology in a hospital radiopharmacy, under appropriate regulatory authority approvals. Multicentre clinical trials of 131I-rituximab radioimmunotherapy have been performed in patients with relapsed or refractory low grade non-Hodgkins lymphoma with therapeutically effective administered activities being determined on the basis of individualised prospective patient dosimetry. A non-myeloablative regimen of 131I-radioimmunotherapy predicated upon a maximum prescribed dose of 0.75 Gy to whole body has been used to minimise myelotoxicity in patients undergoing radioimmunotherapy, even when they have been heavily pre-treated with chemotherapy and/or there is tumour infiltration of bone marrow greater than 25%. Provided that baseline leucocytes exceeded an absolute neutrophil count of 1.5 x 109/L and platelets > 100 x 109 /L, the incidence of grade IV haematological toxicity was 16% for neutrophils and 4 % for platelets which was self-limited. The red marrow radiation absorbed dose in selected patients receiving 131I activities estimated to deliver 0.75 Gy to whole body was calculated to be less than 2 Gy using Monte Carlo methodology on post therapy CT/SPECT imaging. Predictive dosimetry was performed by serial whole body imaging following IV administration of a standard 200 MBq 131I-rituximab tracer and determination of individual pharmacokinetics of the radiolabelled antibody in each patient. A standard dose of 375 mg/m2 unlabelled rituximab (MabThera) was administered IV immediately prior to the tracer and therapy doses of 131I-rituximab to minimise nonspecific uptake of the radiolabelled antibody and to optimise the tumour to background activity. The administration of a standard course of 4 cycles of cold rituximab (MabThera) in association with the prescribed maximum activity of 131I-rituximab constitutes

  8. Understanding cervical cancer in the context of developing countries

    Directory of Open Access Journals (Sweden)

    Farhad Ali

    2012-01-01

    Full Text Available Cancer is one of the leading causes of deaths worldwide. Among the women, gynecological cancers are most common. Cervical cancer is a main gynecological cancer of the women. The global burden of cervical cancer is disproportionately high among the developing countries where 85 per cent of the estimated 493, 000 new cases and 273, 000 deaths occur worldwide. There are several dimensions of the problem. Cervical cancer is a problem where people are poor, where the socio-economic status of the women is low and sometimes specific ethnicity also posses additional risk to the women to develop cervical cancer. Human papillomavirus infection is a main risk factor for the cervical cancer however there are some other factors which increase the risk. Among them some are number of sexual partners, age of first sexual intercourse, infection of sexually transmitted diseases, use of hormonal contraceptives, parity, age, smoking, food and diet. Apart from these factors, some other issues, such as policy on cancer, capacity of health system, socio-economic and cultural factors and awareness among the women are also associated with the cervical cancer related morbidity and mortality across the developing countries. There some interventions which give promising results in terms of reducing cervical cancer related morbidity and mortality. Among them visual inspection of cervix with acetic acid followed by treatment is one such effective method.

  9. Discovery and development of sulforaphane as a cancer chemopreventive phytochemical

    Institute of Scientific and Technical Information of China (English)

    Yuesheng ZHANG; Li TANG

    2007-01-01

    Sulforaphane (SF) is a phytochemical that displays both anticarcinogenic and anticancer activity. SF modulates many cancer-related events, including suscep-tibility to carcinogens, cell death, cell cycle, angiogenesis, invasion and metastasis.We review its discovery and development as a cancer chemopreventive agent with the intention of encouraging further research on this important compound and facilitating the identification and development of new phytochemicals for cancer prevention.

  10. Simultaneous radiotherapy and radioimmunotherapy of malignant gliomas with anti-EGFR antibody labelled with iodine 125. Preliminary results

    International Nuclear Information System (INIS)

    In this paper we present the preliminary results of a prospective trial of the efficacy of simultaneous radiotherapy and anti-EGFR 125I radioimmunotherapy of malignant gliomas with 2 years' total survival as the end-point, raising the question whether anti-EGFR 125I radioimmunotherapy influences the disease-free survival in these patients. Patients with anaplastic astrocytoma or primary glioblastoma were previously treated by a macroscopically radical neurosurgical approach and randomized either to radiotherapy + radioimmunotherapy arm or treated by radiotherapy alone. Seven patients were included in the group with radioimmunotherapy, among them five with GBM and two with AA, and five patients in the control arm. Patients were irradiated to 60 Gy using three-dimensional conformal noncoplanar techniques. Anti-EGFR 125I monoclonal antibody 425 radioimmunotherapy (50 mCi/course) was started during 4. week of radiotherapy and was repeated three times in one week intervals. Time of follow-up ranges between 2 and 10 months in the anti-EGFR 125I radioimmunotherapy arm and 4 and 9 months in the control arm. Recurrence was diagnosed in all patients in the EGFR 125I group with a lethal outcome in two of them and in 4 patients in the control group. Median time to recurrence was 2 and 5 months respectively. Taking into account early recurrences observed, we propose to continue the studies on the efficacy of adjuvant anti-EGFR 125I radioimmunotherapy in a selected group of patients in whom the greatest benefit may be expected on the basis of molecular studies, among them EGFR expression investigation. (author)

  11. Radioimmunotherapy for treatment of acute myeloid leukaemia and myelodysplastic syndrome. Conceptual chances

    International Nuclear Information System (INIS)

    The prognosis of patients with acute myeloid leukaemia (AML) has improved considerably by introduction of aggressive consolidation chemotherapy and haematopoietic stem cell transplantation (SCT). Nevertheless, only 20-30% of patients with AML achieve long-term disease-free survival after SCT. The most common cause of treatment failure is relapse. Additionally, mortality rates are significantly increased by therapy-related causes such as toxicity of chemotherapy and complications of SCT. Including radioimmunotherapies in the treatment of AML and myelodyplastic syndrome (MDS) allows for the achievement of a pronounced antileukaemic effect for the reduction of relapse rates on the one hand. On the other hand, no increase of acute toxicity and later complications should be induced. These effects are important for the primary reduction of tumour cells as well as for the myelblative conditioning before SCT. This paper provides a systematic and critical review of the currently used radionuclides and immunoconjugates for the treatment of AML and MDS and summarizes the literature on primary tumour cell reductive radioimmunotherapies on the one hand and conditioning radioimmunotherapies before SCT on the other hand. (orig.)

  12. Cancer developing among atom-bomb survivors

    International Nuclear Information System (INIS)

    Cancer (with the exception of leukemia) which had often been observed among atom bomb survivors was discussed. Prevalence of thyroid carcinoma was high in the people who had been exposed to more than 50 rad of the atomic radiation. A great difference in prevalence of cancer was seen between irradiated people whose age had been under 20 years at the time of exposure and non-irradiated. More women than men had papillary adenocarcinoma. The highest prevalence was seen 16 to 20 years after exposure to atomic radiation, but there was no difference in prevalence between those from Hiroshima and from Nagasaki. Lung cancer comprised 89% of all cancers of the people whose age was 50 years and over. Most of them had been exposed to atomic radiation of more than 300 rad. The type was cellular retrograde cancer. The prevalence of gastric carcinoma was low, and breast cancer occurred at an early age before menopause. The occurrence of cancer in juvenile survivors was several times higher in the patients who had been exposed to atomic radiation of more than 100 rad than in non-irradiated. These values indicate that cancer occurs more frequently than leukemia does in such survivors. (Kanao, N.)

  13. Nutrients Impact the Pathogenesis and Development of Colorectal Cancer

    Science.gov (United States)

    Du, Wan; Fang, Jing-Yuan

    2016-01-01

    Background Colorectal cancer is a commonly diagnosed cancer and the cause of many cancer deaths worldwide. Nutrients might be crucial in the pathogenesis and development of colorectal cancer. Although a number of studies have demonstrated the potential effects of nutrients, many challenges still remain Summary A tremendous amount of research has emerged concerning the roles of nutrients in colorectal cancer during the past decades. Here, we review the latest research progress on nutrients, including vitamins, folic acid, calcium, selenium and dietary fiber, involved in colorectal cancer prevention Key Message Nutrients are commonly consumed in foods or dietary supplements. It is clear that nutrients could play an important role and influence colorectal cancer outcomes. The relationship between nutrients and colorectal risk is complex. Vitamins, folic acid, calcium, selenium and dietary fiber have been proposed as potential agents to prevent colorectal cancer. However, some studies found that these nutrients did not reduce the incidence of colorectal cancer Practical Implications The supplementary dose of nutrients, the length of time required to observe the effects and confounding factors during the study might influence the role of nutrients in the prevention of colorectal cancer. Therefore, more evidence from ongoing clinical trials with different population groups and longer follow-up periods is critical to determine the relationship between nutrients and colorectal cancer. PMID:27403415

  14. Left behind: cancer disparities in the developed world.

    Science.gov (United States)

    Dixit, Niharika; Crawford, Gregory B; Lemonde, Manon; Rittenberg, Cynthia N; Fernández-Ortega, Paz

    2016-08-01

    Huge advances have been made in cancer treatments over recent decades; however, significant disparities still exist in the developed world on the basis of race, socioeconomic status, education level, geographical location, and immigration status and in the United States, insurance status. Cancer disparities persist in the continuum of cancer care from risk factors, screening, diagnosis, treatment, survivorship, and end-of-life care. The causes of disparities are complex and multifactorial. The MASCC (Multinational Association of Supportive Care in Cancer) Education Study Group would like to propose a framework of cancer disparities from a social perspective utilizing "social determinants of health" as delineated by the World Health Organization and highlight an unmet need for research and policy innovations to address cancer disparities in developed world. PMID:27052305

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

    OpenAIRE

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

    2008-01-01

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

  16. FISH CANCER DEVELOPED BY ENVIRONMENTAL POLLUTANTS

    Directory of Open Access Journals (Sweden)

    Madhuri S.

    2012-10-01

    Full Text Available The pollution of rivers and streams with chemical contaminants has become one of the most critical environmental problems. Fish living in a polluted water reservoir use the contaminated water to rinse their gills; this results in the deposition of polycyclic aromatic hydrocarbons (PAHs in the fish body. Contamination of foodstuffs by heavy metals such as arsenic, cadmium, chromium, nickel and lead has poses a potential carcinogenic threat to humans. Arsenic and cadmium appear to be the most harmful to the fish. Several cancers in fish appear to be the result of exposure to different environmental pollutants/chemicals. High frequencies of liver and skin cancers in brown bullheads are associated with high concentrations of PAHs and some metals in the environmental sediments. Taking these facts in view, the present article gives the emphasis on the fish cancer caused by various environmental pollutants, suggesting that fish species are truly suffer from different cancers/tumours.

  17. Substantial contribution of extrinsic risk factors to cancer development | Office of Cancer Genomics

    Science.gov (United States)

    Recent research has highlighted a strong correlation between tissue-specific cancer risk and the lifetime number of tissue-specific stem-cell divisions. Whether such correlation implies a high unavoidable intrinsic cancer risk has become a key public health debate with the dissemination of the 'bad luck' hypothesis. Here we provide evidence that intrinsic risk factors contribute only modestly (less than ~10-30% of lifetime risk) to cancer development.

  18. Development of cancer-targeting radionanoparticles

    International Nuclear Information System (INIS)

    Here we report the first formulation of porphyrin coated albumin nanoparticles that are coated by porphyrin which is known to be cancer-tropic agent and used for photodynamic therapy for the cancer. Albumin nanoparticles were prepared by solvent extraction method. Mean particle size of the prepares nanoparticles was dependent on the addition rate of ethanol and ranged from 100 to 200 nm. Hematoporphyrin IX dihydrochloride (HP) were chosen for surface modification of albumin nanoparticle. The amino residue of surface albumin nanoparticles (ep, from lysine) was linked with carboxyl group of HP. HP coated albumin nanoparticles were purified by ultracentrifugation and characterized by modulated differential calorimetry (MDSC), x-ray diffractometry, field-emission scanning electron microsope (FE-SEM), transmission electron microsopope (TEM). HP modified albumin nanoparticles showed a good chelation efficiency (more that 95 %) against 99mTc, being applicable to cancer targeting radio-nanoparticles. The uptake of HP modified albumin nanoparticles in CT-26 and A549 cancer cell line was greater than that of normal albumin anaopraticles, proving that HP modified albumin nanoparticles is valuable for the cancer targeting radio isotope nanoparticles

  19. Development of cancer-targeting radionanoparticles

    Energy Technology Data Exchange (ETDEWEB)

    Sim, C. G.; Yang, S. G.; Jin, H. E. [Seoul National University, Seoul (Korea, Republic of)

    2007-06-15

    Here we report the first formulation of porphyrin coated albumin nanoparticles that are coated by porphyrin which is known to be cancer-tropic agent and used for photodynamic therapy for the cancer. Albumin nanoparticles were prepared by solvent extraction method. Mean particle size of the prepares nanoparticles was dependent on the addition rate of ethanol and ranged from 100 to 200 nm. Hematoporphyrin IX dihydrochloride (HP) were chosen for surface modification of albumin nanoparticle. The amino residue of surface albumin nanoparticles (ep, from lysine) was linked with carboxyl group of HP. HP coated albumin nanoparticles were purified by ultracentrifugation and characterized by modulated differential calorimetry (MDSC), x-ray diffractometry, field-emission scanning electron microsope (FE-SEM), transmission electron microsopope (TEM). HP modified albumin nanoparticles showed a good chelation efficiency (more that 95 %) against {sup 99m}Tc, being applicable to cancer targeting radio-nanoparticles. The uptake of HP modified albumin nanoparticles in CT-26 and A549 cancer cell line was greater than that of normal albumin anaopraticles, proving that HP modified albumin nanoparticles is valuable for the cancer targeting radio isotope nanoparticles.

  20. Comparative Efficacy of 177Lu and 90Y for Anti-CD20 Pretargeted Radioimmunotherapy in Murine Lymphoma Xenograft Models

    Energy Technology Data Exchange (ETDEWEB)

    Frost, Sophia; Frayo, Shani; Miller, Brian W.; Orozco, Johnnie J.; Booth, Garrett C.; Hylarides, Mark; Lin, Yukang; Green, Damian J.; Gopal, Ajay K.; Pagel, John M.; Back, Tom; Fisher, Darrell R.; Press, Oliver W.

    2015-03-01

    Pretargeted radioimmunotherapy (PRIT) is a multi-step method of selectively delivering high doses of radiotherapy to tumor cells while minimizing exposure to surrounding tissues. Yttrium-90 (90Y) and lutetium-177 (177Lu) are two of the most promising beta-particle emitting radionuclides used for radioimmunotherapy, which despite having similar chemistries differ distinctly in terms of radiophysical features. These differences may have important consequences for the absorbed dose to tumors and normal organs. Whereas 90Y has been successfully applied in a number of preclinical and clinical radioimmunotherapy settings, there have been few published pretargeting studies with 177Lu. We therefore compared the therapeutic potential of targeting either 90Y or 177Lu to human B-cell lymphoma xenografts in mice.

  1. Development of computer aided diagnosis for lung cancer CT screening

    International Nuclear Information System (INIS)

    The introduction of low dose lung cancer helical CT screening to the clinical site has been the fundamental basis of research on Computer Aided Diagnosis (CAD) using thoracic CT images. Our purpose is the early detection of lung cancer leading to its early treatment, in order to reduce the mortality of lung cancer. From multi-slice CT, lung cancer screening has been activated more. Since CT screening contains a lot of images compared with the conventional X-ray, research and development on the utilization of computer and network using the new diagnosis support technology is required. Due to the demand from actual clinical site, the research group from The University of Tokushima has started the research and development of CAD using lung cancer CT images. We report the result and the future works. (author)

  2. Standard Operating Procedure for Prospective Individualised Dosimetry for ([131])I-rituximab Radioimmunotherapy of Non-Hodgkin's Lymphoma.

    Science.gov (United States)

    Calais, Phillipe J; Turner, J Harvey

    2012-09-01

    Radioimmunotherapy (RIT) is an attractive therapy for non-Hodgkin's lymphoma (NHL) as it allows targeted tumor irradiation which provides a cytotoxic effect significantly greater than that of the immune-mediated effects of a non-radioactive, or 'cold', antibody alone. Anti-CD20 antibodies such as rituximab are ideal for RIT, as not only is it easily iodinated, but the CD20 antigen is found on more than 95% of B-cell NHL. A standard operating procedure (SOP) has been formulated for personalized prospective dosimetry for safe, effective outpatient (131)I-rituximab RIT of NHL. Over five years, experience of treatment of outpatients with (131)I-rituximab was analyzed with respect to critical organ radiation dose in patients and radiation exposure of their carers. This radiation safety methodology has been refined; and offers the potential for safe, practical application to outpatient (131)I-rituximab RIT of lymphoma in general and in developing countries in particular. Given endorsement and sanction of this SOP by local regulatory authorities the personalized dosimetry paradigm will facilitate incorporation of RIT into the routine clinical practice of therapeutic nuclear oncology worldwide. PMID:23372448

  3. Telomerase targeting in cancer treatment : new developments

    NARCIS (Netherlands)

    Helder, MN; de Jong, S; de Vries, EGE; van der Zee, AGJ

    1999-01-01

    Telomerase, a ribonucleoprotein expressed in 85% of advanced cancers but not in most somatic cells, compensates for telomeric DNA erosion and as such stabilizes cell immortality. Telomerase inhibition might restore mortality in tumor cells. Recent progress is illustrated in studies on telomerase and

  4. Studies on the optimization of leukemia and non-Hodgkin lymphoma therapies using opioids, chemotherapy and radioimmunotherapy

    International Nuclear Information System (INIS)

    Despite complex treatment schedules for cancer, the occurrence of resistances and relapses is a major concern in oncology. Hence, novel treatment options are needed. In this thesis, different approaches using radioimmunotherapy and the opioid D,L-methadone alone or in combination with doxorubicin were analyzed regarding their cytotoxic potential and the triggered signalling pathways in sensitive and resistant leukaemia and non-Hodgkin lymphoma (NHL). The radioimmunoconjugates [Bi-213]anti-CD33 and [Bi-213]anti-CD20 for treatment of acute myeloid leukaemia (AML) or NHL, respectively, were applied exemplary for the use of targeted alpha-therapies (TAT). Depending on the analyzed cell lines, the used activity concentrations and specific activities (MBq/μg antibody) apoptosis was induced abrogating radio- and chemo-cross-resistances specifically. The cell death was caspase-dependent activating the mitochondrial pathway and was executed by downregulation of the anti-apoptotic proteins XIAP and Bcl-xL. D,L-Methadone induces apoptosis in vitro and in vivo in opioid-receptor (OR) expressing cells depending on the OR density and the used concentrations. Resistances could be overcome and proliferation was inhibited. In combination with doxorubicin, a synergistic effect regarding cytotoxicity in ex vivo patient cells and cell lines was observed. This effect depends on the increase of doxorubicin uptake co-administering D,L-methadone whereas doxorubicin enhances OR expression. The activation of OR leads to the downregulation of cAMP playing a pivotal role in apoptosis induction. In vivo, the therapeutic potential of D,L-methadone alone or in combination with doxorubicin could be proven as mice transplanted with human T-ALL-cells could be identified as tumour free. In summary, these studies show that TAT using [Bi-213]anti-CD33 and [Bi-213]anti-CD20 as well as the opioid D,L-methadone harbour the potential to optimize conventional treatment modalities for leukaemia and NHL.

  5. Preparation and radiolabeling of a lyophilized (kit) formulation of DOTA-rituximab with 90Y and 111In for domestic radioimmunotherapy and radioscintigraphy of Non-Hodgkin’s Lymphoma

    OpenAIRE

    Gholipour, Nazila; Jalilian, Amir Reza; Khalaj, Ali; Johari-Daha, Fariba; Yavari, Kamal; Sabzevari, Omid; Khanchi, Ali Reza; AKHLAGHI, MEHDI

    2014-01-01

    Background On the basis of results of our previous investigations on 90Y-DTPA-rituximab and in order to fulfil national demands to radioimmunoconjugates for radioscintigraphy and radioimmunotherapy of Non-Hodgkin’s Lymphoma (NHL), preparation and radiolabeling of a lyophilized formulation (kit) of DOTA-rituximab with 111In and 90Y was investigated. Methods 111In and 90Y with high radiochemical and radionuclide purity were prepared by 112Cd (p,2n)111In nuclear reaction and a locally developed ...

  6. Development of PROSTVAC immunotherapy in prostate cancer.

    Science.gov (United States)

    Singh, Parminder; Pal, Sumanta K; Alex, Anitha; Agarwal, Neeraj

    2015-01-01

    PROSTVAC immunotherapy is a heterologous prime-boost regimen of two different recombinant pox-virus vectors; vaccinia as the primary immunotherapy, followed by boosters employing fowlpox, to provoke immune responses against prostate-specific antigen. Both vectors contain transgenes for prostate-specific antigen and a triad of T-cell costimulatory molecules (TRICOM). In a placebo-controlled Phase II trial of men with minimally symptomatic, chemotherapy-naive metastatic castration-resistant prostate cancer, PROSTVAC was well tolerated and associated with a 44% reduction in death. With a novel mechanism of action, and excellent tolerability, PROSTVAC has the potential to dramatically alter the treatment landscape of prostate cancer, not only as a monotherapy, but also in combination with other novel agents, such as immune check point inhibitors and novel androgen receptor blockers. A Phase III trial recently completed accrual. PMID:26235179

  7. Graphic Evolution Witness the Development of Lung Cancer Translational Research

    Directory of Open Access Journals (Sweden)

    Chao ZHANG

    2016-06-01

    Full Text Available Lung cancer treatment has altered from conventional chemotherapy to targeted treatment, which now has been turned to the immunotherapy. Translational research has played an irreplaceable role during this progression which graphic evolution has witnessed. The evolution has gone through forest plot, KM-curve, waterfall plot, spider plot and timeline-area, showing us the refining concept and gradual process of lung cancer treatment undergoing from community towards individual. Even though the latest immunotherapy is getting increasingly hot, the result isn’t quite expected. Meanwhile, the limitations of conventional treatment still exist which require further research. This article will primarily illustrate the development of translational research of lung cancer via the aspect of curve evolution and analysis some abortive clinical trials in lung cancer surgery for inspiring the next graphic style and lung cancer treatment.

  8. [Graphic Evolution Witness the Development of Lung Cancer Translational Research].

    Science.gov (United States)

    Zhang, Chao; Zhong, Wenzhao

    2016-06-20

    Lung cancer treatment has altered from conventional chemotherapy to targeted treatment, which now has been turned to the immunotherapy. Translational research has played an irreplaceable role during this progression which graphic evolution has witnessed. The evolution has gone through forest plot, KM-curve, waterfall plot, spider plot and timeline-area, showing us the refining concept and gradual process of lung cancer treatment undergoing from community towards individual. Even though the latest immunotherapy is getting increasingly hot, the result isn't quite expected. Meanwhile, the limitations of conventional treatment still exist which require further research. This article will primarily illustrate the development of translational research of lung cancer via the aspect of curve evolution and analysis some abortive clinical trials in lung cancer surgery for inspiring the next graphic style and lung cancer treatment. PMID:27335306

  9. Oral cancer in Libya and development of regional oral cancer registries: A review.

    Science.gov (United States)

    BenNasir, E; El Mistiri, M; McGowan, R; Katz, R V

    2015-10-01

    The aims of this paper are three-fold: (1) to summarize the current epidemiological data on oral cancer in Libya as reported in the published literature and as compared to other national oral cancer rates in the region; (2) to present both the history of the early development, and future goals, of population-based oral cancer tumor registries in Libya as they partner with the more established regional and international population-based cancer tumor registries; and, (3) to offer recommendations that will likely be required in the near future if these nascent, population-based Libyan oral cancer registries are to establish themselves as on-going registries for describing the oral cancer disease patterns and risk factors in Libya as well as for prevention and treatment. This comprehensive literature review revealed that the current baseline incidence of oral cancer in Libya is similar to those of other North Africa countries and China, but is relatively low compared to the United Kingdom, the United States, and India. The recently established Libyan National Cancer Registry Program, initiated in 2007, while envisioning five cooperating regional cancer registries, continues to operate at a relatively suboptimal level. Lack of adequate levels of national funding continue to plague its development…and the accompanying quality of service that could be provided to the Libyan people. PMID:26644751

  10. Proliferation and the advantage of longer-lived radionuclides in radioimmunotherapy

    OpenAIRE

    Howell, Roger W.; Goddu, S. Murty; Rao, Dandamudi V.

    1998-01-01

    In our previous study we used the linear-quadratic model [J. Nucl. Med. 35, 1861 (1994)] to confirm our initial finding, based on the time-dose-fractionation model [J. Nucl. Med. 34, 1801 (1993)], that longer-lived radionuclides (e.g., 32P, 91Y) can offer a substantial therapeutic advantage over the shorter-lived radionuclides presently used in radioimmunotherapy (e.g., 90Y). The original calculations using the linear-quadratic (LQ) model did not account for proliferation of the tumor and cri...

  11. Radioimmunotherapy with tositumomab and iodine-131 tositumomab for non-Hodgkin’s lymphoma

    OpenAIRE

    Andemariam, Biree; Leonard, John P.

    2007-01-01

    With the success of targeted monoclonal antibody therapy in non-Hodgkin’s lymphoma, attempts were made to further improve efficacy through the addition of a radioisotope. A goal of radioimmunotherapy is to utilize the monoclonal antibody to deliver radiation to a tumor bed with relatively limited toxicity to the surrounding normal tissues. I-131 Tositumomab is an iodine-131 labeled anti-CD20 murine IgG2a monoclonal antibody and is one of two FDA-approved radioimmunotherapeutic drugs for patie...

  12. Cooperative research and development opportunities with the National Cancer Institute

    Science.gov (United States)

    Sybert, Kathleen

    1991-01-01

    The Office of Technology Development (OTD) of the National Cancer Institute (NCI) is responsible for negotiating Cooperative Research and Development Agreements (CRADAs), whereby the knowledge resulting from NCI investigators' government-sponsored research is developed in collaboration with universities and/or industry into new products of importance for the diagnosis and treatment of cancer and acquired immunodeficiency syndrome (AIDS). The NCI has recently executed a unique 'clinical trials' CRADA and is developing a model agreement based upon it for the development and commercialization of products for the diagnosis and treatment of cancer and AIDS. NCI drug screening, preclinical testing, clinical trials, and AIDS program capabilities form the basis for this new technology development/technology transfer vehicle. NCI's extensive drug screening program and 'designer foods' program serve as potential sources of investigational new drugs (INDs) and cancer preventatives. Collaborations between NCI and pharmaceutical companies having the facilities, experience, and expertise necessary to develop INDs into approved drugs available to the public are being encouraged where the companies have proprietary rights to INDs, or where NCI has proprietary rights to INDs and invites companies to respond to a collaborator announcement published in the Federal Register. The joint efforts of the NCI and the chosen collaborator are designed to generate the data necessary to obtain pharmaceutic regulatory approval from the Food and Drug Administration (FDA) to market the drugs developed, and thereby make them available to health care providers for the diagnosis and treatment of cancer and AIDS.

  13. [Development of Nucleic Acid-Based Adjuvant for Cancer Immunotherapy].

    Science.gov (United States)

    Kobiyama, Kouji; Ishii, Ken J

    2015-09-01

    Since the discovery of the human T cell-defined tumor antigen, the cancer immunotherapy field has rapidly progressed, with the research and development of cancer immunotherapy, including cancer vaccines, being conducted actively. However, the disadvantages of most cancer vaccines include relatively weak immunogenicity and immune escape or exhaustion. Adjuvants with innate immunostimulatory activities have been used to overcome these issues, and these agents have been shown to enhance the immunogenicity of cancer vaccines and to act as mono-therapeutic anti-tumor agents. CpG ODN, an agonist for TLR9, is one of the promising nucleic acid-based adjuvants, and it is a potent inducer of innate immune effector functions. CpG ODN suppresses tumor growth in the absence of tumor antigens and peptide administration. Therefore, CpG ODN is expected to be useful as a cancer vaccine adjuvant as well as a cancer immunotherapy agent. In this review, we discuss the potential therapeutic applications and mechanisms of CpG ODN for cancer immunotherapy. PMID:26469159

  14. Human-Mouse Dosimetry in Clinical Radioimmunotherapy - Special Emphasis on Pediatric Applications

    International Nuclear Information System (INIS)

    Monoclonal antibody ('MAB') has been developed for targeting secretory alpha-fetoprotein in hepatic tissue. We have used these MABs for radioimmunotherapy and dose planning of recurrent hepatoblastoma, a rare childhood malignancy This MAB has been labelled with In- 111 and Y-90 for clinical purposes, and can be applied for diagnosis and therapy of liver neoplasms. Physiology based pharmacokinetic (PBPK) modeling and simulation is a useful method for prediction of biodistribution of macromolecules, it can enhance our understanding of the underlying mechanisms and hence may help in rational design of diagnostic and therapeutic agents. Here we also discuss PBPK modeling and simulation of this MAB in mice without tumor and in a pediatric patient. In the clinical study, radiopharmacokinetic parameters for this MAB (111In-DOTA-hAFP31 IgG) were calculated after serial quantitative whole body scans in a child with hepatoblastoma. A 3-D dose planning computer program was used to calculate tumor doses for In-111 and Y-90, the active tumor was delineated on PET/CT images and tumor dose calculation was done based on the In-111-MAB SPECT data using dose point kernel approach both for In-111 and Y-90. The results were compared with MIRD doses obtained for organs in SPECT imaging field, i.e. bone marrow, heart, kidneys, liver, spleen, lungs. The simulated results were fitted to experimental time series data by varying parameters which were not fixed a priori. From quantitative serial imaging based on 8 whole body images at 0-168 hrs using In-111- MAB, the half-lives of spleen, lungs, kidneys and whole body were 502 hrs, 230 hrs, 193 hrs and 490 hrs, respectively. The measured blood half-life was 132 hrs, after a total MAB dose of 50 mg and In-111 activity of 105 MBq. The presumed Y-90 dose based on this kinetic behavior was 43 MBq which should had given 0.3Gy bone marrow dose with assumption of bone marrow: blood ratio 0.4 for IgG. The calculated MIRD Y-90 doses were for cardiac

  15. Cathelicidin suppresses colon cancer development by inhibition of cancer associated fibroblasts

    Directory of Open Access Journals (Sweden)

    Cheng M

    2014-12-01

    Full Text Available Michelle Cheng,1,* Samantha Ho,1,* Jun Hwan Yoo,1,2,* Deanna Hoang-Yen Tran,1,* Kyriaki Bakirtzi,1 Bowei Su,1 Diana Hoang-Ngoc Tran,1 Yuzu Kubota,1 Ryan Ichikawa,1 Hon Wai Koon1 1Center for Inflammatory Bowel Diseases, Division of Digestive Diseases, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA, USA; 2Digestive Disease Center, CHA University Bundang Medical Center, Seongnam, Republic of Korea *These authors share co-first authorship Background: Cathelicidin (LL-37 in humans and mCRAMP in mice represents a family of endogenous antimicrobial and anti-inflammatory peptides. Cancer-associated fibroblasts can promote the proliferation of colon cancer cells and growth of colon cancer tumors. Methods: We examined the role of cathelicidin in the development of colon cancer, using subcutaneous human HT-29 colon-cancer-cell-derived tumor model in nude mice and azoxymethane- and dextran sulfate-mediated colon cancer model in C57BL/6 mice. We also determined the indirect antitumoral mechanism of cathelicidin via the inhibition of epithelial–mesenchymal transition (EMT of colon cancer cells and fibroblast-supported colon cancer cell proliferation. Results: Intravenous administration of cathelicidin expressing adeno-associated virus significantly reduced the size of tumors, tumor-derived collagen expression, and tumor-derived fibroblast expression in HT-29-derived subcutaneous tumors in nude mice. Enema administration of the mouse cathelicidin peptide significantly reduced the size and number of colonic tumors in azoxymethane- and dextran sulfate-treated mice without inducing apoptosis in tumors and the adjacent normal colonic tissues. Cathelicidin inhibited the collagen expression and vimentin-positive fibroblast expression in colonic tumors. Cathelicidin did not directly affect HT-29 cell viability, but did significantly reduce tumor growth factor-ß1-induced EMT of colon cancer cells. Media conditioned by the

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

    OpenAIRE

    Ashworth Alan; Lord Christopher J

    2010-01-01

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

  17. Inguinal hernia developed after radical retropubic surgery for prostate cancer

    OpenAIRE

    Chung, Choon Sik; Jeong, Gyu Young; Kim, Seung Han; Lee, Dong Keun

    2013-01-01

    Purpose In this retrospective study, we aimed to compare the clinical characteristics of inguinal hernia developed after radical retropubic surgery for prostate cancer to the hernia without previous radical prostatectomy. Methods Twenty-three patients (group A) who had radical retropubic surgery for prostate cancer underwent laparoscopic or open tension-free inguinal hernia repair from March 2007 to February 2011. Nine hundred and forty patients (group B) without previous radical retropubic s...

  18. Optimizing lutetium 177-anti-carbonic anhydrase IX radioimmunotherapy in an intraperitoneal clear cell renal cell carcinoma xenograft model

    NARCIS (Netherlands)

    Muselaers, C.H.J.; Oosterwijk, E.; Bos, D.L.; Oyen, W.J.G.; Mulders, P.F.A.; Boerman, O.C.

    2014-01-01

    A new approach in the treatment of clear cell renal carcinoma (ccRCC) is radioimmunotherapy (RIT) using anti-carbonic anhydrase IX (CAIX) antibody G250. To investigate the potential of RIT with lutetium 177 (177Lu)-labeled G250, we conducted a protein dose escalation study and subsequently an RIT st

  19. Cancer incidence and novel therapies developed in Japan

    Directory of Open Access Journals (Sweden)

    Masaru Iwasaki

    2012-01-01

    Full Text Available According to the ministry of Health, Labour and welfare of Japan, Cancer has been the leading cause of death in Japan since 1981. [1] As per the data in 2010, in Japan, one in every three deaths was due to cancer. [2] The Japanese Government has introduced so far, three terms of 10 years strategies for Cancer control since 1984 till date. The budget allocated for cancer control in 2009 was 52.5 billion yen in Japan. [3] Lung is the leading site for cancer in both males and females in Japan. In males, following the lung, stomach, liver, colon and pancreas are other leading sites while in the females, stomach, colon, pancreas and breast are the other leading sites.[1] In 2006, the cancer incidence was 694,000 and the male cancer incidence was 1.4 times as large as that of females. The peak age for cancer deaths in males is their fifties while in the females it is the sixties among Japanese. In addition to the conventional treatments such as surgery, radiotherapy and chemotherapy, some of other therapies in practice in Japan are the Hyperthermia [4] that uses high temperatures to kill or damage the cancer cells, the Ion Beam therapy using proton beams [5] to damage the DNA of the cells as cancer cells have high rate of cell divisions and lesser ability to repair DNA damage, the molecular targeted therapies that interfere with a specific molecular target involved in tumour growth and progression [6] and most importantly the autologous cell based Immunotherapies. Modern Cancer Immunotherapy started in the 1970s in Japan. The immunopotentiators using compounds from Bacteria, Beta Glucans from fungi were the first forms of modern Immunotherapy. Then was the era of direct injection of cytokines such as Interleukins, Interferons etc. The adverse effects associated with the injection of cytokines led to development of cell based Immunotherapies in the 1980s. [7] Immuno-cell therapies involve isolation of immune cells which are then processed and re

  20. Contribution of customised dosimetry for small animal to the treatments of cancers by metabolic radiotherapy

    International Nuclear Information System (INIS)

    This research thesis first reports a bibliographical study which addressed the use of ionizing radiations in cancer therapy (evolution from ionizing radiation to metabolic radiotherapy, biological and physical parameters, and absorbed dose in metabolic radiotherapy) and the role imagery has in customised dosimetry (absorbed dose calculation methods, determination of cumulative activity, dosimetric models for S factor calculation). Then, the author presents a software which has been specifically developed for the creation of dosimetric models, and reports its validation. He reports the comparison between different dosimetric models in the case of mice. He highlights two applications of the developed tool: radio-immunotherapy and metabolic radiotherapy. He finally proposes a general discussion on the impact of small animal dosimetry on metabolic radiotherapy

  1. Thyroid cancer development in Chernobyl including new additional results

    International Nuclear Information System (INIS)

    Full text: We have been studying the etiology of thyroid cancer development among the exposed people in Hiroshima. In 1993, we have proposed the hypothesis of oncology model of thyroid cancer development in children following the nuclear power plant accident in Chernobyl, and then related studies has been done in Chernobyl and also in Hiroshima. Following findings are included. Urinary iodine level was lower in Chernobyl than in Hiroshima. Stimulation of ret oncogene in thyroid cancer tissues, and appearance of nuclear abnormalities of thyroid follicular cells were found higher rate among the exposed people. Sensitivity of TSH-receptor in thyroid tissues (TSH-R mRNA expression) was higher while young. Synergistic effect of TSH-R mRNA and ER mRNA expressions were found in both of normal tissues and cancer tissues in thyroid, but it was more apparent in cancer tissues. These findings gave the additional proofs on the hypothesis of thyroid cancer development in Chernobyl. Including these results, we like to present the importance of thyroid for the health of the exposed people in Chernobyl

  2. Combined radioimmunotherapy and external irradiation for solid tumors in the mouse

    International Nuclear Information System (INIS)

    Objective: To evaluate the optimal external irradiation dose and potential benefits with different treatment timing strategies and sequence of combined external irradiation and radioimmunotherapy for solid tumors in the mouse. Methods: TS1, a monoclonal antibody directed against anticytokeratin 8, can specifically combined with anticytokeratin in the necrotic parts of tumors. Mab TS1 was iodinated with 131I. Among sixty nude mice with tumor cells xenografts (human cervical squamous carcinoma) used in this study, twenty-four were used in a pilot experiment to determine the appropriate level of external irradiation dose by observing the tumor growth inhibition while thirty-six were used in the experiment proper which were divided into 6 groups and given different treatment protocols. Total accumulated dose, percentage of injected activity per gram of tumor tissue and accumulated dose per injected activity were compared between these different groups. Results: In the pilot experiment, the tumor growth was inhibited markedly by 20 Gy of external irradiation, but the response did not significantly increase when the dose was increased to 26 Gy. In the experiment proper, the highest yields in terms of total accumulated dose, percentage of injected activity per gram of tumor tissue and accumulated dose per injected activity were seen in the group which received external irradiation prior to Mab injection. Conclusions: Enhanced effects can be achieved by combined external irradiation with radioimmunotherapy using the monoclonal anticytokeratin antibody 131I-TS1. 20 Gy of external irradiation should be given prior to Mab injection

  3. Radioimmunotherapy for non-Hodgkin's lymphoma: A review for radiation oncologists

    International Nuclear Information System (INIS)

    Purpose: The aim of this study was to review advances in radioimmunotherapy (RIT) for non-Hodgkin's lymphoma (NHL) and to discuss the role of Radiation oncologist in administering this important new form of biologically targeted radiotherapy. Methods and Materials: A review of articles and abstracts on the clinical efficacy, safety, and radiation safety of yttrium Y 90 (9Y) ibritumomab tiuxetan (Zevalin) and iodine I 131 tositumomab (Bexxar) was performed. Results: The clinical efficacy of RIT in NHL has been shown in numerous clinical trials of 9Y ibritumomab tiuxetan and 131I tositumomab. Both agents have produced significant responses in patients with low-grade, follicular, or transformed NHL, including patients with disease that had not responded or had responded poorly to previous chemotherapy or immunotherapy. Reversible toxicities such as neutropenia, thrombocytopenia, and anemia are the most common adverse events with both agents. Conclusions: Radioimmunotherapy is safe and effective in many patients with B-cell NHL. 9Y ibritumomab tiuxetan and 131I tositumomab can produce clinically meaningful and durable responses even in patients in whom chemotherapy has failed. Treatment with RIT requires a multispecialty approach and close communication between Radiation oncologist and other members of the treatment team. Radiation oncologist plays an important role in treating patients with RIT and monitoring them for responses and adverse events after treatment

  4. Chromatin Repressive Complexes in Stem Cells, Development, and Cancer

    DEFF Research Database (Denmark)

    Laugesen, Anne; Helin, Kristian

    2014-01-01

    The chromatin environment is essential for the correct specification and preservation of cell identity through modulation and maintenance of transcription patterns. Many chromatin regulators are required for development, stem cell maintenance, and differentiation. Here, we review the roles of the...... polycomb repressive complexes, PRC1 and PRC2, and the HDAC1- and HDAC2-containing complexes, NuRD, Sin3, and CoREST, in stem cells, development, and cancer, as well as the ongoing efforts to develop therapies targeting these complexes in human cancer. Furthermore, we discuss the role of repressive...... complexes in modulating thresholds for gene activation and their importance for specification and maintenance of cell fate....

  5. Cancer stem cells: a new approach to tumor development

    Directory of Open Access Journals (Sweden)

    Natália Cristina Ciufa Kobayashi

    2015-02-01

    Full Text Available Many theories have been proposed to explain the origins of cancer. Currently, evidences show that not every tumor cell is capable of initiating a tumor. Only a small part of the cancer cells, called cancer stem cells (CSCs, can generate a tumor identical to the original one, when removed from human tumors and transplanted into immunosuppressed mice. The name given to these cells comes from the resemblance to normal stem cells, except for the fact that their ability to divide is infinite. These cells are also affected by their microenvironment. Many of the signaling pathways, such as Wnt, Notch and Hedgehog, are altered in this tumoral subpopulation, which also contributes to abnormal proliferation. Researchers have found several markers for CSCs; however, much remains to be studied, or perhaps a universal marker does not even exist, since they vary among tumor types and even from patient to patient. It was also found that cancer stem cells are resistant to radiotherapy and chemotherapy. This may explain the re-emergence of the disease, since they are not completely eliminated and minimal amounts of CSCs can repopulate a tumor. Once the diagnosis in the early stages greatly increases the chances of curing cancer, identifying CSCs in tumors is a goal for the development of more effective treatments. The objective of this article is to discuss the origin of cancer according to the theory of stem cell cancer, as well as its markers and therapies used for treatment.

  6. Approaches to improve development methods for therapeutic cancer vaccines.

    Science.gov (United States)

    Ogi, Chizuru; Aruga, Atsushi

    2015-04-01

    Therapeutic cancer vaccines are an immunotherapy that amplify or induce an active immune response against tumors. Notably, limitations in the methodology for existing anti-cancer drugs may subsist while applying them to cancer vaccine therapy. A retrospective analysis was performed using information obtained from ClinicalTrials.gov, PubMed, and published articles. Our research evaluated the optimal methodologies for therapeutic cancer vaccines based on (1) patient populations, (2) immune monitoring, (3) tumor response evaluation, and (4) supplementary therapies. Failure to optimize these methodologies at an early phase may impact development at later stages; thus, we have proposed some points to be considered during the early phase. Moreover, we compared our proposal with the guidance for industry issued by the US Food and Drug Administration in October 2011 entitled "Clinical Considerations for Therapeutic Cancer Vaccines". Consequently, while our research was aligned with the guidance, we hope it provides further insights in order to predict the risks and benefits and facilitate decisions for a new technology. We identified the following points for consideration: (1) include in the selection criteria the immunological stage with a prognostic value, which is as important as the tumor stage; (2) select immunological assays such as phenotype analysis of lymphocytes, based on their features and standardize assay methods; (3) utilize optimal response criteria for immunotherapy in therapeutic cancer vaccine trials; and (4) consider supplementary therapies, including immune checkpoint inhibitors, for future therapeutic cancer vaccines. PMID:25746315

  7. Molecular mechanisms of prostate cancer development

    Czech Academy of Sciences Publication Activity Database

    Souček, Karel; Lincová, Eva; Staršíchová, Andrea; Pernicová, Zuzana; Vondráček, Jan; Machala, M.; Kozubík, Alois

    Brno, 2008. s. 11. ISBN 978-80-7013-474-0. [Aktuální problematika genetické toxikologie, 31. pracovní dny České a slovenské společnosti pro mutagenezi zevním prostředím Československé biologické společnosti. 12.05.2008-14.05.2008, Brno] R&D Projects: GA ČR(CZ) GA310/07/0961; GA ČR(CZ) GA204/07/0834 Institutional research plan: CEZ:AV0Z50040507; CEZ:AV0Z50040702 Keywords : prostate cancer * neuroendocrine differentiation * inflammation Subject RIV: BO - Biophysics

  8. Development of novel radiosensitizers for cancer therapy

    CERN Document Server

    Akamatsu, K

    2002-01-01

    The novel radiosensitizers for cancer therapy, which have some atoms with large X-ray absorption cross sections, were synthesized. The chemical and radiation (X-rays, W target, 100kVp) toxicities and the radiosensitivities to LS-180 human colon adenocarcinoma cells were also evaluated. 2,3,4,5,6-pentabromobenzylalcohol (PBBA) derivatives were not radiosensitive even around the maximum concentration. On the other hand, the hydrophilic sodium 2,4,6-triiodobenzoate (STIB) indicated meaningful radiosensitivity to the cells. Moreover, the membrane-specific radiosensitizers, cetyl fluorescein isthiocyanate (cetyl FITC), cetyl eosin isothiocyanate (cetyl br-FITC), cetyl erythrosin isothiocyanate (cetyl I-FITC), which aim for the membrane damage by X-ray photoabsorption on the target atoms, were localized in the plasma membrane. As the results of the colony formation assay, it was found that both cetyl FITC are similarly radiosensitive. In this report, we demonstrate the synthetic methods of the radiosensitizers, the...

  9. A silent crisis: Cancer treatment in developing countries

    International Nuclear Information System (INIS)

    A dramatic rise in cancer across the developing world is stretching already limited resources and equipment. Shortages of qualified staff and equipment are growing constraints to treating cancer effectively. Some 5,000 radiotherapy machines are presently needed to help patients fight cancer. But the entire developing world has only about 2,200 such machines. Experts predict a long-term crisis in managing cancer, with an estimated five million new patients requiring radiation therapy every year. Meeting the challenge is not simply a matter of providing appropriate equipment. There must be sufficient trained and knowledgeable staff with clinical and medical physics expertise to deliver a safe and effective radiation dose. Appropriate facilities and radiation protection infrastructure for monitoring and regulatory control are needed. Moreover, cancer treatment must be carried out in a comprehensive context of prevention, early diagnosis, and adequate follow-up care. Providing essential equipment and training of staff to safely treat cancer patients in the developing world is of increasing importance to the IAEA. The Agency has assisted Ethiopia, Ghana, Mongolia, Namibia, and Uganda in establishing their first radiotherapy facilities. The IAEA also provides ongoing support to some 80 developing Member States in upgrading their radiotherapy facilities and providing staff with suitable training. Dosimetry and medical physics are an integral part of any medical treatment that uses ionizing radiation. With computerization, improved techniques are increasingly being used in developing countries to plan and treat patients in a wide range of medical therapies including teletherapy, brachytherapy, and the use of open drinkable or injectable sources. The IAEA works in partnership with the World Health Organisation (WHO) on most of its cancer projects. The WHO works to address the full spectrum of the health-disease continuum from prevention to end-of-life care. The role of the

  10. Quality of working life of cancer survivors: development of a cancer-specific questionnaire

    OpenAIRE

    de Jong, Merel; Tamminga, Sietske J; de Boer, Angela G. E. M.; Frings-Dresen, Monique H. W.

    2015-01-01

    Purpose The aim of this study was to generate, and select quality of working life issues for the development of an initial version of the Quality of Working Life Questionnaire for Cancer Survivors (QWLQ-CS). Methods Quality of working life issues were generated through focus groups with cancer survivors and oncological occupational physicians, and interviews with employers, supervisors, and organization officers. A selection of these quality of working life issues was made based on relevance ...

  11. Development of lung cancer CT screening operating support system

    Science.gov (United States)

    Ishigaki, Rikuta; Hanai, Kozou; Suzuki, Masahiro; Kawata, Yoshiki; Niki, Noboru; Eguchi, Kenji; Kakinuma, Ryutaro; Moriyama, Noriyuki

    2009-02-01

    In Japan, lung cancer death ranks first among men and third among women. Lung cancer death is increasing yearly, thus early detection and treatment are needed. For this reason, CT screening for lung cancer has been introduced. The CT screening services are roughly divided into three sections: office, radiology and diagnosis sections. These operations have been performed through paper-based or a combination of paper-based and an existing electronic health recording system. This paper describes an operating support system for lung cancer CT screening in order to make the screening services efficient. This operating support system is developed on the basis of 1) analysis of operating processes, 2) digitalization of operating information, and 3) visualization of operating information. The utilization of the system is evaluated through an actual application and users' survey questionnaire obtained from CT screening centers.

  12. Development of A Mouse Model of Menopausal Ovarian Cancer

    Directory of Open Access Journals (Sweden)

    Elizabeth R. Smith

    2014-02-01

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

  13. The Influence of Hormonal Factors on the Risk of Developing Cervical Cancer and Pre-Cancer

    DEFF Research Database (Denmark)

    Roura, Esther; Travier, Noémie; Waterboer, Tim; de Sanjosé, Silvia; Bosch, F Xavier; Pawlita, Michael; Pala, Valeria; Weiderpass, Elisabete; Margall, Núria; Dillner, Joakim; Gram, Inger T; Tjønneland, Anne; Munk, Christian; Palli, Domenico; Khaw, Kay-Tee; Overvad, Kim; Clavel-Chapelon, Françoise; Mesrine, Sylvie; Fournier, Agnès; Fortner, Renée T; Ose, Jennifer; Steffen, Annika; Trichopoulou, Antonia; Lagiou, Pagona; Orfanos, Philippos; Masala, Giovanna; Tumino, Rosario; Sacerdote, Carlotta; Polidoro, Silvia; Mattiello, Amalia; Lund, Eiliv; Peeters, Petra H; Bueno-de-Mesquita, H B As; Quirós, J Ramón; Sánchez, María-José; Navarro, Carmen; Barricarte, Aurelio; Larrañaga, Nerea; Ekström, Johanna; Lindquist, David; Idahl, Annika; Travis, Ruth C; Merritt, Melissa A; Gunter, Marc J; Rinaldi, Sabina; Tommasino, Massimo; Franceschi, Silvia; Riboli, Elio; Castellsagué, Xavier

    2016-01-01

    BACKGROUND: In addition to HPV, high parity and hormonal contraceptives have been associated with cervical cancer (CC). However, most of the evidence comes from retrospective case-control studies. The aim of this study is to prospectively evaluate associations between hormonal factors and risk of...... developing cervical intraepithelial neoplasia grade 3 (CIN3)/carcinoma in situ (CIS) and invasive cervical cancer (ICC). METHODS AND FINDINGS: We followed a cohort of 308,036 women recruited in the European Prospective Investigation into Cancer and Nutrition (EPIC) Study. At enrollment, participants.......7). CONCLUSIONS: Even though HPV is the necessary cause of CC, our results suggest that several hormonal factors are risk factors for cervical carcinogenesis. Adherence to current cervical cancer screening guidelines should minimize the increased risk of CC associated with these hormonal risk factors....

  14. Enhancing target/nontarget ratios in radioimmunotherapy: nonspecific human gammaglobulin versus other modalities

    International Nuclear Information System (INIS)

    Full text: The central problem in using radiobioconjugates in therapy is maximising the target/nontarget ratios. Unlike radioimmunoscintigraphy where temporal subtraction of early and late images or clinical context interpretation can be used, radioimmunotherapy and dosimetry demand the highest ratios for the safe use of such radiobioconjugates: frying the tumour without frying the patient. Simultaneously efforts to obtain greater biological specificity are underway in solid tumour therapy comparable to targeting the idiotypes of B cell tumours, and both peptides and newer antibodies are being explored. For increasing tumour localization pre-targetting using either the avidin/biotin approach or bispecific antibodies looking at a chelate in addition to a tumour antigen is being extensively researched. An alternative approach is to reduce nonspecific uptake particularly in the reticuloendothelial system especially the large mass of the liver. Degalactosylation of the antibodies to reduce affinity of the Fc fragment to galactosyl receptors in the liver, or using designer antibody constructs devoid of the Fc fragment: Fab, Fab 2, Fab 3, Fab n or scFv based constructs has been attempted. An inexpensive approach that we have conceived and used is the use of nonspecific human gammaglobulin prior to radioimmunoconjugate administration. This has been done utilizing commercially available inexpensive 16.5 gms% human immunoglobulin preparations(BHARGLOB)rather than the highly expensive IVIG such as Sandoglobulin used in autoimmune disease therapy Aims: To devise optimal schedules for using nonspecific human gammaglobulin for reducing nontarget uptake. Methods: Prior to clinical studies several different large molecular weight agents were evaluated in experimental animals bearing human tumour xenografts, including dextran,hetastarch and gammaglobulin.Gammaglobulin was chosen as the most convenient to administer. In clinical studies various schedules were tried giving Bharglob

  15. Targeting hedgehog signaling in cancer: research and clinical developments

    Directory of Open Access Journals (Sweden)

    Xie J

    2013-10-01

    Full Text Available Jingwu Xie, Christopher M Bartels, Scott W Barton, Dongsheng GuWells Center for Pediatric Research, Division of Hematology and Oncology, Department of Pediatrics, Indiana University Simon Cancer Center, Indiana University, Indianapolis, IN, USAAbstract: Since its first description in Drosophila by Drs Nusslein-Volhard and Wieschaus in 1980, hedgehog (Hh signaling has been implicated in regulation of cell differentiation, proliferation, tissue polarity, stem cell maintenance, and carcinogenesis. The first link of Hh signaling to cancer was established through studies of Gorlin syndrome in 1996 by two independent teams. Later, it was shown that Hh signaling may be involved in many types of cancer, including skin, leukemia, lung, brain, and gastrointestinal cancers. In early 2012, the US Food and Drug Administration approved the clinical use of Hh inhibitor Erivedge/vismodegib for treatment of locally advanced and metastatic basal cell carcinomas. With further investigation, it is possible to see more clinical applications of Hh signaling inhibitors. In this review, we will summarize major advances in the last 3 years in our understanding of Hh signaling activation in human cancer, and recent developments in preclinical and clinical studies using Hh signaling inhibitors.Keywords: hedgehog, smoothened, PTCH1, cancer, signal transduction, clinical trials, animal model

  16. Radiotherapy in Palliative Cancer Care: Development and Implementation

    International Nuclear Information System (INIS)

    It is estimated that in 2008 there were over 12 million new cancer diagnoses and 7 million cancer deaths worldwide. The World Health Organisation (WHO) predicts that cancer rates will increase from 10 million to 24 million in the next 50 years. More than half of cancer cases will be diagnosed in low income nations, where 80% or more of patients will have incurable disease at diagnosis. In situations where most patients are diagnosed with incurable disease or where curative treatment is logistically unavailable, as is the case in many low income countries, the allocation of limited health care resources should reflect a greater emphasis on palliative care. Ironically, access to palliative care is greater in health care systems with well developed infrastructures and facilities for prevention, early detection, and curative treatment of cancer. To provide comprehensive cancer care, a multidisciplinary approach is needed. This maximizes the available treatments and interventions, whilst ensuring a cost effective and ethically sound approach to the treatment of patients at each stage of the disease. Barriers to palliative care may result from its low prioritization in health care policy and education. The WHO expert committee on cancer pain and palliative care report of 1990 called for the integration of efforts directed at maintaining patient quality of life through all stages of cancer treatment. As a result supportive interventions aimed at improving quality of life are needed for patients undergoing both curative and palliative cancer treatment. The International Atomic Energy Agency is currently collaborating with the Open Society Institute to develop palliative care programmes in Eastern Europe, Africa and India, as well as supporting programmes in other regions of the world, through the International Palliative Care Initiative. OSI partners with the IAEA's Programme of Action for Cancer Therapy, the World Health Organization, the International Agency for Research

  17. Engineering an antibody with picomolar affinity to DOTA chelates of multiple radionuclides for pretargeted radioimmunotherapy and imaging

    Energy Technology Data Exchange (ETDEWEB)

    Orcutt, Kelly Davis; Slusarczyk, Adrian L. [Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139 (United States); Cieslewicz, Maryelise [Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139 (United States); Ruiz-Yi, Benjamin [Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139 (United States); Bhushan, Kumar R. [Division of Hematology/Oncology, Beth Israel Deaconess Medical Center, Boston, MA 02215 (United States); Frangioni, John V. [Division of Hematology/Oncology, Beth Israel Deaconess Medical Center, Boston, MA 02215 (United States); Department of Radiology, Beth Israel Deaconess Medical Center, Boston, MA 02215 (United States); Wittrup, K. Dane, E-mail: wittrup@mit.ed [Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139 (United States); Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139 (United States); Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139 (United States)

    2011-02-15

    Introduction: In pretargeted radioimmunotherapy (PRIT), a bifunctional antibody is administered and allowed to pre-localize to tumor cells. Subsequently, a chelated radionuclide is administered and captured by cell-bound antibody while unbound hapten clears rapidly from the body. We aim to engineer high-affinity binders to 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) chelates for use in PRIT applications. Methods: We mathematically modeled antibody and hapten pharmacokinetics to analyze hapten tumor retention as a function of hapten binding affinity. Motivated by model predictions, we used directed evolution and yeast surface display to affinity mature the 2D12.5 antibody to DOTA, reformatted as a single chain variable fragment (scFv). Results: Modeling predicts that for high antigen density and saturating bsAb dose, a hapten-binding affinity of 100 pM is needed for near-maximal hapten retention. We affinity matured 2D12.5 with an initial binding constant of about 10 nM to DOTA-yttrium chelates. Affinity maturation resulted in a 1000-fold affinity improvement to biotinylated DOTA-yttrium, yielding an 8.2{+-}1.9 picomolar binder. The high-affinity scFv binds DOTA complexes of lutetium and gadolinium with similar picomolar affinity and indium chelates with low nanomolar affinity. When engineered into a bispecific antibody construct targeting carcinoembryonic antigen, pretargeted high-affinity scFv results in significantly higher tumor retention of a {sup 111}In-DOTA hapten compared to pretargeted wild-type scFv in a xenograft mouse model. Conclusions: We have engineered a versatile, high-affinity, DOTA-chelate-binding scFv. We anticipate it will prove useful in developing pretargeted imaging and therapy protocols to exploit the potential of a variety of radiometals.

  18. Engineering an antibody with picomolar affinity to DOTA chelates of multiple radionuclides for pretargeted radioimmunotherapy and imaging

    International Nuclear Information System (INIS)

    Introduction: In pretargeted radioimmunotherapy (PRIT), a bifunctional antibody is administered and allowed to pre-localize to tumor cells. Subsequently, a chelated radionuclide is administered and captured by cell-bound antibody while unbound hapten clears rapidly from the body. We aim to engineer high-affinity binders to 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) chelates for use in PRIT applications. Methods: We mathematically modeled antibody and hapten pharmacokinetics to analyze hapten tumor retention as a function of hapten binding affinity. Motivated by model predictions, we used directed evolution and yeast surface display to affinity mature the 2D12.5 antibody to DOTA, reformatted as a single chain variable fragment (scFv). Results: Modeling predicts that for high antigen density and saturating bsAb dose, a hapten-binding affinity of 100 pM is needed for near-maximal hapten retention. We affinity matured 2D12.5 with an initial binding constant of about 10 nM to DOTA-yttrium chelates. Affinity maturation resulted in a 1000-fold affinity improvement to biotinylated DOTA-yttrium, yielding an 8.2±1.9 picomolar binder. The high-affinity scFv binds DOTA complexes of lutetium and gadolinium with similar picomolar affinity and indium chelates with low nanomolar affinity. When engineered into a bispecific antibody construct targeting carcinoembryonic antigen, pretargeted high-affinity scFv results in significantly higher tumor retention of a 111In-DOTA hapten compared to pretargeted wild-type scFv in a xenograft mouse model. Conclusions: We have engineered a versatile, high-affinity, DOTA-chelate-binding scFv. We anticipate it will prove useful in developing pretargeted imaging and therapy protocols to exploit the potential of a variety of radiometals.

  19. Development of cancer therapy facility of HANARO

    International Nuclear Information System (INIS)

    Facilities of the research and clinical treatments of neutron capture therapy using HANARO are developed, and they are ready to install. They are BNCT irradiation facility and prompt gamma neutron activatiion analysis facility. Since every horizontal neutron facility of HANARO is long and narrow tangential beam tube, it is analysed that sufficient epithermal neutrons for the BNCT cannot be obtained but sufficient thermal neutrons can be obtained by a filter composed of silicon and bismuth single crystals. Since the thermal neutron penetaration increases significantly when the crystals are cooled, a filter cooled by liquid nitrogen is developed. So as to avoid interference with the reactor operation, a water shutter is developed. The irradiation room is designed for the temporary surgical operation as well. Handling tools to remove activated beam port plug and to install water shutter and filter are developed. The basic structure of the irradiation room is already installed and most of other parts are ready to install. Since no free beam port is available for the prompt gamma neutron activation analysis, a method obtaining almost pure thermal neutrons by the vertical diffraction of extra beam for the polarized neutron spectrometer is developed. This method is confirmed by analysis and experiments to give high enough neutron beam. Equipment and devices are provided to install this facility

  20. Development of a Barbershop-Based Cancer Communication Intervention

    Science.gov (United States)

    Holt, Cheryl L.; Wynn, Theresa A.; Lewis, Ivey; Litaker, Mark S.; Jeames, Sanford; Huckaby, Francine; Stroud, Leonardo; Southward, Penny L.; Simons, Virgil; Lee, Crystal; Ross, Louis; Mitchell, Theodies

    2009-01-01

    Purpose: Prostate and colorectal cancer (CRC) rates are disproportionately high among African-American men. The purpose of this paper is to describe the development of an intervention in which barbers were trained to educate clients about early detection for prostate and CRC. Design/methodology/approach: Working with an advisory panel of local…

  1. Business models and opportunities for cancer vaccine developers.

    Science.gov (United States)

    Kudrin, Alex

    2012-10-01

    Despite of growing oncology pipeline, cancer vaccines contribute only to a minor share of total oncology-attributed revenues. This is mainly because of a limited number of approved products and limited sales from products approved under compassionate or via early access entry in smaller and less developed markets. However revenue contribution from these products is extremely limited and it remains to be established whether developers are breaking even or achieving profitability with existing sales. Cancer vaccine field is well recognized for high development costs and risks, low historical rates of investment return and high probability of failures arising in ventures, partnerships and alliances. The cost of reimbursement for new oncology agents is not universally acceptable to payers limiting the potential for a global expansion, market access and reducing probability of commercial success. In addition, the innovation in cancer immunotherapy is currently focused in small and mid-size biotech companies and academic institutions struggling for investment. Existing R&D innovation models are deemed unsustainable in current "value-for-money" oriented healthcare environment. New business models should be much more open to collaborative, networked and federated styles, which could help to outreach global, markets and increase cost-efficiencies across an entire value chain. Lessons learned from some developing countries and especially from South Korea illustrate that further growth of cancer vaccine industry will depends not only on new business models but also will heavily rely on regional support and initiatives from different bodies, such as governments, payers and regulatory bodies. PMID:22894953

  2. Design of clinical trials for therapeutic cancer vaccines development.

    Science.gov (United States)

    Mackiewicz, Jacek; Mackiewicz, Andrzej

    2009-12-25

    Advances in molecular and cellular biology as well as biotechnology led to definition of a group of drugs referred to as medicinal products of advanced technologies. It includes gene therapy products, somatic cell therapeutics and tissue engineering. Therapeutic cancer vaccines including whole cell tumor cells vaccines or gene modified whole cells belong to somatic therapeutics and/or gene therapy products category. The drug development is a multistep complex process. It comprises of two phases: preclinical and clinical. Guidelines on preclinical testing of cell based immunotherapy medicinal products have been defined by regulatory agencies and are available. However, clinical testing of therapeutic cancer vaccines is still under debate. It presents a serious problem since recently clinical efficacy of the number of cancer vaccines has been demonstrated that focused a lot of public attention. In general clinical testing in the current form is very expensive, time consuming and poorly designed what may lead to overlooking of products clinically beneficial for patients. Accordingly regulatory authorities and researches including Cancer Vaccine Clinical Trial Working Group proposed three regulatory solutions to facilitate clinical development of cancer vaccines: cost-recovery program, conditional marketing authorization, and a new development paradigm. Paradigm includes a model in which cancer vaccines are investigated in two types of clinical trials: proof-of-principle and efficacy. The proof-of-principle trial objectives are: safety; dose selection and schedule of vaccination; and demonstration of proof-of-principle. Efficacy trials are randomized clinical trials with objectives of demonstrating clinical benefit either directly or through a surrogate. The clinical end points are still under debate. PMID:19835869

  3. Perspectives of development of thyroid cancers in Belarus

    International Nuclear Information System (INIS)

    This paper gives an overview on the total number if thyroid cancers observed in Belarus after the Chernobyl accident among children, discusses possible sources of the observed increase over expected cases and compares these observations with predictive calculations using different risk coefficients published in the literature. To this purpose exposure estimates of the thyroid are made for children living in three selected areas. Different radioecological, dosimetric and other reasons make it very difficult to obtain reliable dose estimates for these victims, and the use of published risk coefficients for the assessment of future developments of the thyroid cancer incidence rates results in predictions which do not agree too well with the observations

  4. Developing a nanoparticle test for prostate cancer scoring

    Directory of Open Access Journals (Sweden)

    Huo Qun

    2012-03-01

    Full Text Available Abstract Background Over-diagnosis and treatment of prostate cancer has been a major problem in prostate cancer care and management. Currently the most relevant prognostic factor to predict a patient's risk of death due to prostate cancer is the Gleason score of the biopsied tissue samples. However, pathological analysis is subjective, and the Gleason score is only a qualitative estimate of the cancer malignancy. Molecular biomarkers and diagnostic tests that can accurately predict prostate tumor aggressiveness are rather limited. Method We report here for the first time the development of a nanoparticle test that not only can distinguish prostate cancer from normal and benign conditions, but also has the potential to predict the aggressiveness of prostate cancer quantitatively. To conduct the test, a prostate tissue lysate sample is spiked into a blood serum or human IgG solution and the spiked sample is incubated with a citrate-protected gold nanoparticle solution. IgG is known to adsorb to citrate-protected gold nanoparticles to form a "protein corona" on the nanoparticle surface. From this study, we discovered that certain tumor-specific molecules can interact with IgG and change the adsorption behavior of IgG to the gold nanoparticles. This change is reflected in the nanoparticle size of the assay solution and detected by a dynamic light scattering technique. Assay data were analyzed by one-way ANOVA for multiple variant analysis, and using the Student t-test or nonparametric Mann-Whitney U-tests for pairwise analyses. Results An inverse, quantitative correlation of the average nanoparticle size of the assay solution with tumor status and histological diagnostic grading was observed from the nanoparticle test. IgG solutions spiked with prostate tumor tissue exhibit significantly smaller nanoparticle size than the solutions spiked with normal and benign tissues. The higher grade the tumor is, the smaller the nanoparticle size is. The test

  5. Development and Validation of a Prediction Model to Estimate Individual Risk of Pancreatic Cancer

    OpenAIRE

    Yu, Ami; Woo, Sang Myung; Joo, Jungnam; Yang, Hye-Ryung; Lee, Woo Jin; Park, Sang-Jae; Nam, Byung-Ho

    2016-01-01

    Introduction There is no reliable screening tool to identify people with high risk of developing pancreatic cancer even though pancreatic cancer represents the fifth-leading cause of cancer-related death in Korea. The goal of this study was to develop an individualized risk prediction model that can be used to screen for asymptomatic pancreatic cancer in Korean men and women. Materials and Methods Gender-specific risk prediction models for pancreatic cancer were developed using the Cox propor...

  6. Different ways to improve the clinical effectiveness of radioimmunotherapy in solid tumors

    Directory of Open Access Journals (Sweden)

    Chatal Jean-Francois

    2009-09-01

    Full Text Available Radioimmunotherapy (RIT has been proven effective in the treatment of radiosensitive non-Hodgkin lymphoma but, for radioresistant solid tumors, new approaches are necessary to improve the clinical effectiveness. A real improvement has been the introduction of the pretargeting technology which appeared to be able to significantly increase tumor-to-normal organ uptake ratios.Another very promising approach consists in associating RIT with other treatment modalities. Finally the use of alpha particle-emitting radionuclides such as astatin-211 or bismuth-213 (alpha-RIT should allow to efficiently eradicate disseminated microscopic clusters of tumor cells or isolated tumor cells which fit well with the short path length of alpha particles.

  7. Cancer Development, Progression, and Therapy: An Epigenetic Overview

    Directory of Open Access Journals (Sweden)

    McKenna Longacre

    2013-10-01

    Full Text Available Carcinogenesis involves uncontrolled cell growth, which follows the activation of oncogenes and/or the deactivation of tumor suppression genes. Metastasis requires down-regulation of cell adhesion receptors necessary for tissue-specific, cell–cell attachment, as well as up-regulation of receptors that enhance cell motility. Epigenetic changes, including histone modifications, DNA methylation, and DNA hydroxymethylation, can modify these characteristics. Targets for these epigenetic changes include signaling pathways that regulate apoptosis and autophagy, as well as microRNA. We propose that predisposed normal cells convert to cancer progenitor cells that, after growing, undergo an epithelial-mesenchymal transition. This process, which is partially under epigenetic control, can create a metastatic form of both progenitor and full-fledged cancer cells, after which metastasis to a distant location may occur. Identification of epigenetic regulatory mechanisms has provided potential therapeutic avenues. In particular, epigenetic drugs appear to potentiate the action of traditional therapeutics, often by demethylating and re-expressing tumor suppressor genes to inhibit tumorigenesis. Epigenetic drugs may inhibit both the formation and growth of cancer progenitor cells, thus reducing the recurrence of cancer. Adopting epigenetic alteration as a new hallmark of cancer is a logical and necessary step that will further encourage the development of novel epigenetic biomarkers and therapeutics.

  8. Beta-irradiation used for systemic radioimmunotherapy induces apoptosis and activates apoptosis pathways in leukaemia cells

    International Nuclear Information System (INIS)

    Beta-irradiation used for systemic radioimmunotherapy (RIT) is a promising treatment approach for high-risk leukaemia and lymphoma. In bone marrow-selective radioimmunotherapy, beta-irradiation is applied using iodine-131, yttrium-90 or rhenium-188 labelled radioimmunoconjugates. However, the mechanisms by which beta-irradiation induces cell death are not understood at the molecular level. Here, we report that beta-irradiation induced apoptosis and activated apoptosis pathways in leukaemia cells depending on doses, time points and dose rates. After beta-irradiation, upregulation of CD95 ligand and CD95 receptor was detected and activation of caspases resulting in apoptosis was found. These effects were completely blocked by the broad-range caspase inhibitor zVAD-fmk. In addition, irradiation-mediated mitochondrial damage resulted in perturbation of mitochondrial membrane potential, caspase-9 activation and cytochrome c release. Bax, a death-promoting protein, was upregulated and Bcl-xL, a death-inhibiting protein, was downregulated. We also found higher apoptosis rates and earlier activation of apoptosis pathways after gamma-irradiation in comparison to beta-irradiation at the same dose rate. Furthermore, irradiation-resistant cells were cross-resistant to CD95 and CD95-resistant cells were cross-resistant to irradiation, indicating that CD95 and irradiation used, at least in part, identical effector pathways. These findings demonstrate that beta-irradiation induces apoptosis and activates apoptosis pathways in leukaemia cells using both mitochondrial and death receptor pathways. Understanding the timing, sequence and molecular pathways of beta-irradiation-mediated apoptosis may allow rational adjustment of chemo- and radiotherapeutic strategies. (orig.)

  9. Low incidence of radionecrosis in children treated with conventional radiation therapy and intrathecal radioimmunotherapy.

    Science.gov (United States)

    Kramer, Kim; Pandit-Taskar, Neeta; Zanzonico, Pat; Wolden, Suzanne L; Humm, John L; DeSelm, Carl; Souweidane, Mark M; Lewis, Jason S; Cheung, Nai-Kong V

    2015-06-01

    Radionecrosis is a potentially devastating complication of external beam radiotherapy (XRT). Intraventricular compartmental radioimmunotherapy (cRIT) using (131)I-3F8 or (131)I-8H9 can eradicate malignant cells in the CSF. The incidence of radionecrosis using cRIT (131)I based intraventricular radioimmunotherapy, when used alone or in combination with conventional craniospinal CSI-XRT is unknown. We retrospectively analyzed the incidence of radionecrosis in two cohorts of pediatric patients treated with both CSI-XRT and cRIT at MSKCC since 2003: patients with metastatic CNS neuroblastoma (NB) and medulloblastoma (MB). 94 patients received both CSI-XRT and cRIT, two received cRIT alone, median follow up 41.5 months (6.5-124.8 months). Mean CSI-XRT dose was 28 Gy (boost to the primary tumor site up to 54 Gy) in the MB cohort, and CSI XRT dose 18-21 Gy (boost to 30 Gy for focal parenchymal mass) in the NB cohort. For MB patients, 20 % had focal re-irradiation for a second or more subsequent relapse, mean repeat-XRT dose was 27.5 Gy; seven patients with NB had additional focal XRT. Median CSF cRIT dose was 18.6 Gy in the MB cohort and 32.1 in the NB cohort. One asymptomatic patient underwent resection of 0.6-cm hemorrhagic periventricular white-matter lesion confirmed to be necrosis and granulation tissue, 2.5 years after XRT. The risk of radionecrosis in children treated with XRT and cRIT appears minimal (~1 %). No neurologic deficits secondary to radionecrosis have been observed in long-term survivors treated with both modalities, including patients who underwent re-XRT. Administration of cRIT may safely proceed in patients treated with conventional radiotherapy without appearing to increase the risk of radionecrosis. PMID:25944385

  10. Development of a Multidisciplinary, Multicampus Subspecialty Practice in Endocrine Cancers

    Science.gov (United States)

    Bible, Keith C.; Smallridge, Robert C.; Morris, John C.; Molina, Julian R.; Suman, Vera J.; Copland, John A.; Rubin, Joseph; Menefee, Michael E.; Sideras, Kostandinos; Maples, William J.; McIver, Bryan; Fatourechi, Vahab; Hay, Ian; Foote, Robert L.; Garces, Yolanda I.; Kasperbauer, Jan L.; Thompson, Geoffrey B.; Grant, Clive S.; Richards, Melanie L.; Sebo, Thomas; Lloyd, Ricardo; Eberhardt, Norman L.; Reddi, Honey V.; Casler, John D.; Karlin, Nina J.; Westphal, Sydney A.; Richardson, Ronald L.; Buckner, Jan C.; Erlichman, Charles

    2012-01-01

    Purpose: Relative to more abundant neoplasms, endocrine cancers have been historically neglected, yet their incidence is increasing. We therefore sought to build interest in endocrine cancers, improve physician experience, and develop innovative approaches to treating patients with these neoplasms. Methods: Between 2005 and 2010, we developed a multidisciplinary Endocrine Malignancies Disease Oriented Group involving all three Mayo Clinic campuses (Rochester, MN; Jacksonville, FL; and Scottsdale, AZ). In response to higher demand at the Rochester campus, we sought to develop a Subspecialty Tumor Group and an Endocrine Malignancies Tumor Clinic within the Division of Medical Oncology. Results: The intended groups were successfully formed. We experienced difficulty in integration of the Mayo Scottsdale campus resulting from local uncertainty as to whether patient volumes would be sufficient to sustain the effort at that campus and difficulty in developing enthusiasm among clinicians otherwise engaged in a busy clinical practice. But these obstacles were ultimately overcome. In addition, with respect to the newly formed medical oncology subspecialty endocrine malignancies group, appointment volumes quadrupled within the first year and increased seven times within two years. The number of active therapeutic endocrine malignancies clinical trials also increased from one in 2005 to five in 2009, with all three Mayo campuses participating. Conclusion: The development of subspecialty tumor groups for uncommon malignancies represents an effective approach to building experience, increasing patient volumes and referrals, and fostering development of increased therapeutic options and clinical trials for patients afflicted with otherwise historically neglected cancers. PMID:22942830

  11. Cancer screening: Should cancer screening be essential component of primary health care in developing countries?

    Directory of Open Access Journals (Sweden)

    Saurabh Bobdey

    2015-01-01

    Conclusions: Our study highlights the availability and success of visual screening tools in early detection and mortality reduction of major neoplasia in resource-poor health care settings and recommends implementation of oral and cervical cancer screening as part of assured primary health care package in developing countries.

  12. Radioimmunotherapy of micrometastases in lung with vascular targeted213Bi

    OpenAIRE

    Kennel, S. J.; Boll, R.; Stabin, M; Schuller, H M; Mirzadeh, S

    1999-01-01

    A model system has been used to test the efficacy of vascular targeting of α-particle emitter213Bi for therapy of small, ‘artificial’ metastases in mouse lung. Specific monoclonal antibody (mAb) 201B was used to deliver greater than 30% of the injected dose to lung where tumours had developed due to intravenous injection of cells. Specific213Bi-mAb 201B treatment of BALB/c mammary carcinoma EMT-6 tumours in lung resulted in a dose-dependent destruction of tumours and an extended lifespan of t...

  13. Image correlation: meaning in clinical radioimmunotherapy dosimetry for treatment planning

    International Nuclear Information System (INIS)

    Image correlation has many potential applications in Nuclear Medicine: the combination of the high resolution anatomical delineation of structures as achievable with MRI/CT and the less spatially resolved but functional biochemical images from SPECT, benefits both modalities and is successful in clinical applications. In particular this is fundamental to obtain 1) the volume determination of tumours and normal organs and 2) the quantitation of the activity of radiolabelled antibodies in tumours and normal organs, necessary for the development of treatment strategies. Clinical reports of treatment planning in cerebral gliomas are showed in this paper: the modalities used are CT and SPECT with DTPA. The last has the property of showing the contour of the skull allowing an easier correlation by comparing it to the one that is even more visible by CT. This suggests to use anatomic markers or even surface fitting (Pellizzari algorithm)

  14. [Cancer].

    Science.gov (United States)

    de la Peña-López, Roberto; Remolina-Bonilla, Yuly Andrea

    2016-09-01

    Cancer is a group of diseases which represents a significant public health problem in Mexico and worldwide. In Mexico neoplasms are the second leading cause of death. An increased morbidity and mortality are expected in the next decades. Several preventable risk factors for cancer development have been identified, the most relevant including tobacco use, which accounts for 30% of the cancer cases; and obesity, associated to another 30%. These factors, in turn, are related to sedentarism, alcohol abuse and imbalanced diets. Some agents are well knokn to cause cancer such as ionizing radiation, viruses such as the papilloma virus (HPV) and hepatitis virus (B and C), and more recently environmental pollution exposure and red meat consumption have been pointed out as carcinogens by the International Agency for Research in Cancer (IARC). The scientific evidence currently available is insufficient to consider milk either as a risk factor or protective factor against different types of cancer. PMID:27603890

  15. Development of a conceptual model of cancer caregiver health literacy.

    Science.gov (United States)

    Yuen, E Y N; Dodson, S; Batterham, R W; Knight, T; Chirgwin, J; Livingston, P M

    2016-03-01

    Caregivers play a vital role in caring for people diagnosed with cancer. However, little is understood about caregivers' capacity to find, understand, appraise and use information to improve health outcomes. The study aimed to develop a conceptual model that describes the elements of cancer caregiver health literacy. Six concept mapping workshops were conducted with 13 caregivers, 13 people with cancer and 11 healthcare providers/policymakers. An iterative, mixed methods approach was used to analyse and synthesise workshop data and to generate the conceptual model. Six major themes and 17 subthemes were identified from 279 statements generated by participants during concept mapping workshops. Major themes included: access to information, understanding of information, relationship with healthcare providers, relationship with the care recipient, managing challenges of caregiving and support systems. The study extends conceptualisations of health literacy by identifying factors specific to caregiving within the cancer context. The findings demonstrate that caregiver health literacy is multidimensional, includes a broad range of individual and interpersonal elements, and is influenced by broader healthcare system and community factors. These results provide guidance for the development of: caregiver health literacy measurement tools; strategies for improving health service delivery, and; interventions to improve caregiver health literacy. PMID:25630765

  16. MITOCHONDRIA: INSIGHT TARGET OF DRUG DEVELOPMENT IN CANCER CELLS

    Directory of Open Access Journals (Sweden)

    Md. Ataur Rahman

    2012-09-01

    Full Text Available Mitochondria are involved in different physiological and pathological processes that are crucial for tumor cell physiology, growth and survival and its dysfunction leads to many human abnormalities, including cardiovascular diseases, neurodegenerative diseases, autoimmune disorders and cancer. The present review is focused on the different experimental and therapeutic cancer strategies addressed to either target mitochondria directly, or use mitochondria as mediators of apoptosis, although its total molecular mechanism has not been elucidated. Therefore, the role of mitochondria in the etiology and progression of several function and explore potential therapeutic benefits of targeting mitochondria in the disease processes. Newly evolving advances in disease diagnostics and therapy will further facilitate future growth in the field of mitochondrian biology, where there is a dire need for sensitive and more affordable diagnostic tools and an urgency to develop effective therapies and identify reliable drug to predict accurately the response to a cancer therapy. These approaches to treat mitochondrial dysfunction rationally could lead to selective protection of cells in different tissues and various disease states. To avoid mitochondrial liabilities, routine screens need to be positioned within the drug-development process as targets of drug-induced cytotoxicity or cancer promotion, as regulators of apoptosis, as sources of cell signalling through reactive oxygen species, and mitochondrial control of specific nuclear responses. However, several novel mitochondrial targets are now emerging, including the potential to manipulate the mitochondrial pool to maintain function via biogenesis and mitophagy. Forthcoming insights into the fine regulation of mitochondrial apoptosis will likely open future perspectives for cancer drug development.

  17. Advantage of dose fractionation in monoclonal antibody-targeted radioimmunotherapy

    International Nuclear Information System (INIS)

    Monoclonal antibody (MAb) B72.3 IgG was radiolabeled with 131I and administered to female athymic NCr-nu mice bearing the LS-174T human colon adenocarcinoma xenograft to determine if fractionation of MAb dose had any advantage in tumor therapy. In the LS-174T xenograft, only approximately 30%-60% of tumor cells express the B72.3-reactive TAG-72 antigen. The LS-174T xenograft was used to reflect the heterogeneity of the TAG-72 antigen often seen in biopsy specimens from patients. In contrast to a single 600-muCi dose of 131I-B72.3 IgG where 60% of the animals died from toxic effects, two 300-muCi doses of 131I-B72.3 IgG reduced or eliminated tumor growth in 90% of mice, with only 10% of the animals dying from toxic effects. Dose fractionation even permitted escalation of the dose to three doses of 300 muCi of 131I-B72.3 IgG, resulting in even more extensive tumor reduction or elimination and minimal toxic effects. The use of an isotype-matched control MAb revealed a nonspecific component to tumor growth retardation, but the use of the specific B72.3 IgG demonstrated a much greater therapeutic effect. Tumors that had escaped MAb therapy were analyzed for expression of the B72.3-reactive TAG-72 antigen with the use of the immunoperoxidase method; they were shown to have the same antigenic phenotype as the untreated tumors. We verified tumor elimination by killing the test animals after a 7-week observation period and performing histologic examination of tumor sites. We also monitored toxic effects by histologic examination of numerous organs. These studies thus demonstrate the advantage of dose fractionation of a radiolabeled MAb for tumor therapy. We anticipate that the concept of dose fractionation can be practically applied in radioimmunotherapeutic clinical trials with the development and use of recombinant-chimeric MAbs and modified constructs

  18. New Antibody Conjugates in Cancer Therapy

    Directory of Open Access Journals (Sweden)

    Serengulam V. Govindan

    2010-01-01

    Full Text Available Targeting of radiation, drugs, and protein toxins to cancers selectively with monoclonal antibodies (MAbs has been a topic of considerable interest and an area of continued development. Radioimmunotherapy (RAIT of lymphoma using directly labeled MAbs is of current interest after approval of two radiolabeled anti-CD20 MAbs, as illustrated with the near 100% overall response rate obtained in a recent clinical trial using an investigational radiolabeled anti-CD22 MAb, 90Y-epratuzumab. The advantage of pretargeted RAIT over directly labeled MAbs is continuing to be validated in preclinical models of lymphoma and solid tumors. Importantly, the advantages of combining RAIT with radiation sensitizers, with immunotherapy, or a drug conjugate targeting a different antigen are being studied clinically and preclinically. The area of drug-conjugated antibodies is progressing with encouraging data published for the trastuzumab-DM1 conjugate in a phase I clinical trial in HER2-positive breast cancer. The Dock-and-Lock platform technology has contributed to the design and the evaluation of complex antibody-cytokine and antibody-toxin conjugates. This review describes the advances made in these areas, with illustrations taken from advances made in the authors' institutions.

  19. Radioimmunotherapy with Tenarad, a {sup 131}I-labelled antibody fragment targeting the extra-domain A1 of tenascin-C, in patients with refractory Hodgkin's lymphoma

    Energy Technology Data Exchange (ETDEWEB)

    Aloj, Luigi [Istituto Nazionale Tumori ' ' Fondazione G. Pascale' ' - IRCCS, Struttura Complessa di Medicina Nucleare, Napoli (Italy); D' Ambrosio, Laura; Aurilio, Michela; Morisco, Anna; Caraco' , Corradina; Di Gennaro, Francesca; Lastoria, Secondo [Istituto Nazionale Tumori ' ' Fondazione G. Pascale' ' - IRCCS, Struttura Complessa Medicina Nucleare, Napoli (Italy); Frigeri, Ferdinando; Capobianco, Gaetana; Pinto, Antonio [Istituto Nazionale Tumori ' ' Fondazione G. Pascale' ' - IRCCS, Struttura Complessa di Ematologia Oncologica, Napoli (Italy); Giovannoni, Leonardo; Menssen, Hans D. [Philogen, SpA, Siena (Italy); Neri, Dario [Institute of Pharmaceutical Sciences, ETH, Zurich (Switzerland)

    2014-05-15

    The extra-domain A1 of tenascin-C (TC-A1) is highly expressed in the extracellular matrix of tumours and on newly formed blood vessels and is thus a valuable target for radionuclide therapy. Tenarad is a fully human miniantibody or small immunoprotein (SIP, molecular weight 80 kDa) labelled with {sup 131}I that is derived from a TC-A1-binding antibody. Previous phase I/II studies with a similar compound ({sup 131}I-L19SIP) used for radioimmunotherapy (RIT) have shown preliminary efficacy in a variety of cancer types. In this ongoing phase I/II trial, Tenarad was administered to patients with recurrent Hodgkin's lymphoma (HL) refractory to conventional treatments. Eight patients (four men, four women; age range 19 - 41) were enrolled between April 2010 and March 2011. All patients had received a median of three previous lines of chemotherapy (range three to six) and seven had also undergone autologous stem cell transplantation (ASCT) or bone marrow transplantation. In addition, seven patients received external beam radiation. All patients had nodal disease, constitutional B symptoms and some showed extranodal disease in skeletal bone (four patients), lung (three), liver (two) and spleen (one). Baseline assessments included whole-body FDG PET with contrast-enhanced CT and diagnostic Tenarad planar and SPECT studies. Patients were considered eligible to receive a therapeutic dose of Tenarad (2.05 GBq/m{sup 2}) if tumour uptake was more than four times higher than that of muscle. All patients were eligible and received the therapeutic dose of Tenarad. Only one patient developed grade 4 thrombocytopenia and leucocytopenia, requiring hospitalization and therapeutic intervention. All other patients had haematological toxicity of grade 3 or lower, which resolved spontaneously. At the first response assessment (4 - 6 weeks after therapy), one patient showed a complete response, one showed a partial response (PR) and five had disease stabilization (SD). Five patients

  20. Evolution of animal models in cancer vaccine development.

    Science.gov (United States)

    Wei, Wei-Zen; Jones, Richard F; Juhasz, Csaba; Gibson, Heather; Veenstra, Jesse

    2015-12-16

    Advances in cancer vaccine development are facilitated by animal models reflecting key features of human cancer and its interface with host immunity. Several series of transplantable preneoplastic and neoplastic mouse mammary lesions have been used to delineate mechanisms of anti-tumor immunity. Mimicking immune tolerance to tumor-associated antigens (TAA) such as HER2/neu, transgenic mice developing spontaneous mammary tumors are strong model systems for pre-clinical vaccine testing. In these models, HER2 DNA vaccines are easily administered, well-tolerated, and induce both humoral and cellular immunity. Although engineered mouse strains have advanced cancer immunotherapy, basic shortcomings remain. For example, multiple mouse strains have to be tested to recapitulate genetic regulation of immune tolerance in humans. Outbred domestic felines more closely parallel humans in the natural development of HER2 positive breast cancer and their varying genetic background. Electrovaccination with heterologous HER2 DNA induces robust adaptive immune responses in cats. Importantly, homologous feline HER2 DNA with a single amino acid substitution elicits unique antibodies to feline mammary tumor cells, unlocking a new vaccine principle. As an alternative approach to targeted vaccination, non-surgical tumor ablation such as cryoablation induces anti-tumor immunity via in situ immunization, particularly when combined with toll-like receptor (TLR) agonist. As strategies for vaccination advance, non-invasive monitoring of host response becomes imperative. As an example, magnetic resonance imaging (MRI) and positron emission tomography (PET) scanning following administration of tryptophan metabolism tracer [11C]-alpha-methyl-tryptophan (AMT) provides non-invasive imaging of both tumor growth and metabolic activities. Because AMT is a substrate of indoleamine-pyrrole 2,3-dioxygenase (IDO), an enzyme that produces the immune regulatory molecule kynurenine, AMT imaging can provide

  1. Study of the Accelerator Technology Development for Cancer Radiotherapy

    International Nuclear Information System (INIS)

    The hadronic particle beams including both protons, neutrons and charged particles have been studied for cancer therapy by a number of research centers in several countries during the past two decades. In this paper is briefly discussed concerning the accelerator type and its applications. The future trends are seen in the new technological developments like the use of proton gantries, beam scanning techniques, improved patient handling system and in the increasing precision of treatment. (author)

  2. Common astrocytic programs during brain development, injury and cancer

    OpenAIRE

    Silver, Daniel J.; Steindler, Dennis A.

    2009-01-01

    In addition to radial glial cells of neurohistogenesis, immature astrocytes with stem-cell-like properties cordon off emerging functional patterns in the developing brain. Astrocytes also can be stem cells during adult neurogenesis, and a proposed potency of injury-associated reactive astrocytes has recently been substantiated. Astrocytic cells might additionally be involved in cancer stem cell-associated gliomagenesis. Thus, there are distinguishing roles for stem-cell-like astrocytes during...

  3. 78 FR 33851 - Lung Cancer Patient-Focused Drug Development; Public Meeting

    Science.gov (United States)

    2013-06-05

    ... Impacts That Matter Most to Patients 1. For context, how long ago was your diagnosis of lung cancer? Is... HUMAN SERVICES Food and Drug Administration Lung Cancer Patient-Focused Drug Development; Public Meeting... public comment on Patient-Focused Drug Development for lung cancer. Patient-Focused Drug Development......

  4. (212)Pb-radioimmunotherapy induces G(2) cell-cycle arrest and delays DNA damage repair in tumor xenografts in a model for disseminated intraperitoneal disease.

    Science.gov (United States)

    Yong, Kwon Joong; Milenic, Diane E; Baidoo, Kwamena E; Brechbiel, Martin W

    2012-03-01

    In preclinical studies, targeted radioimmunotherapy using (212)Pb-TCMC-trastuzumab as an in vivo generator of the high-energy α-particle emitting radionuclide (212)Bi is proving an efficacious modality for the treatment of disseminated peritoneal cancers. To elucidate mechanisms associated with this therapy, mice bearing human colon cancer LS-174T intraperitoneal xenografts were treated with (212)Pb-TCMC-trastuzumab and compared with the nonspecific control (212)Pb-TCMC-HuIgG, unlabeled trastuzumab, and HuIgG, as well as untreated controls. (212)Pb-TCMC-trastuzumab treatment induced significantly more apoptosis and DNA double-strand breaks (DSB) at 24 hours. Rad51 protein expression was downregulated, indicating delayed DNA double-strand damage repair compared with (212)Pb-TCMC-HuIgG, the nonspecific control. (212)Pb-TCMC-trastuzumab treatment also caused G(2)-M arrest, depression of the S phase fraction, and depressed DNA synthesis that persisted beyond 120 hours. In contrast, the effects produced by (212)Pb-TCMC-HuIgG seemed to rebound by 120 hours. In addition, (212)Pb-TCMC-trastuzumab treatment delayed open chromatin structure and expression of p21 until 72 hours, suggesting a correlation between induction of p21 protein and modification in chromatin structure of p21 in response to (212)Pb-TCMC-trastuzumab treatment. Taken together, increased DNA DSBs, impaired DNA damage repair, persistent G(2)-M arrest, and chromatin remodeling were associated with (212)Pb-TCMC-trastuzumab treatment and may explain its increased cell killing efficacy in the LS-174T intraperitoneal xenograft model for disseminated intraperitoneal disease. PMID:22238365

  5. Autophagy as a target for cancer therapy: new developments

    International Nuclear Information System (INIS)

    Autophagy is an evolutionarily conserved lysosomal degradation pathway that eliminates cytosolic proteins, macromolecules, organelles, and protein aggregates. Activation of autophagy may function as a tumor suppressor by degrading defective organelles and other cellular components. However, this pathway may also be exploited by cancer cells to generate nutrients and energy during periods of starvation, hypoxia, and stress induced by chemotherapy. Therefore, induction of autophagy has emerged as a drug resistance mechanism that promotes cancer cell survival via self-digestion. Numerous preclinical studies have demonstrated that inhibition of autophagy enhances the activity of a broad array of anticancer agents. Thus, targeting autophagy may be a global anticancer strategy that may improve the efficacy of many standard of care agents. These results have led to multiple clinical trials to evaluate autophagy inhibition in combination with conventional chemotherapy. In this review, we summarize the anticancer agents that have been reported to modulate autophagy and discuss new developments in autophagy inhibition as an anticancer strategy

  6. CT Lung Cancer Screening Program Development: Part 2.

    Science.gov (United States)

    Yates, Teri

    2015-01-01

    Radiology administrators must use innovative strategies around clinical collaboration and marketing to ensure that patients access the service in sufficient numbers. Radiology Associates of South Florida in collaboration with Baptist Health South Florida have developed a successful lung cancer screening program. The biggest factors in their success have been the affordability of their service and the quality of the program. Like mammography, lung cancer screening programs serve as an entry point to other services that generate revenue for the hospital. Patients may require further evaluation in the form of more imaging or surgical services for biopsy. Part 1 provided background and laid out fundamentals for starting a program. Part 2 focuses on building patient volume, marketing, and issues related to patient management after the screen is performed. PMID:26314180

  7. Using lessons from breast, cervical, and colorectal cancer screening to inform the development of lung cancer screening programs.

    Science.gov (United States)

    Armstrong, Katrina; Kim, Jane J; Halm, Ethan A; Ballard, Rachel M; Schnall, Mitchell D

    2016-05-01

    Multiple advisory groups now recommend that high-risk smokers be screened for lung cancer by low-dose computed tomography. Given that the development of lung cancer screening programs will face many of the same issues that have challenged other cancer screening programs, the National Cancer Institute-funded Population-based Research Optimizing Screening through Personalized Regimens (PROSPR) consortium was used to identify lessons learned from the implementation of breast, cervical, and colorectal cancer screening that should inform the introduction of lung cancer screening. These lessons include the importance of developing systems for identifying and recruiting eligible individuals in primary care, ensuring that screening centers are qualified and performance is monitored, creating clear communication standards for reporting screening results to referring physicians and patients, ensuring follow-up is available for individuals with abnormal test results, avoiding overscreening, remembering primary prevention, and leveraging advances in cancer genetics and immunology. Overall, this experience emphasizes that effective cancer screening is a multistep activity that requires robust strategies to initiate, report, follow up, and track each step as well as a dynamic and ongoing oversight process to revise current screening practices as new evidence regarding screening is created, new screening technologies are developed, new biological markers are identified, and new approaches to health care delivery are disseminated. Cancer 2016;122:1338-1342. © 2016 American Cancer Society. PMID:26929386

  8. Structural pathways of cytokines may illuminate their roles in regulation of cancer development and immunotherapy

    OpenAIRE

    Emine Guven-Maiorov; Saliha Ece Acuner-Ozbabacan; Ozlem Keskin; Attila Gursoy; Ruth Nussinov

    2014-01-01

    Cancers 2014, 6, 663-683; doi:10.3390/cancers6020663 cancers ISSN 2072-6694 www.mdpi.com/journal/cancers Review Structural Pathways of Cytokines May Illuminate Their Roles in Regulation of Cancer Development and Immunotherapy Emine Guven-Maiorov 1, Saliha Ece Acuner-Ozbabacan 1, Ozlem Keskin 1, Attila Gursoy 1 and Ruth Nussinov 2,3,* 1 Center for Computational Biology and Bioinformatics and College of Engineering, Koc University, Rumelifeneri Yolu, 34450 Sariyer ...

  9. Role of viruses in the development of breast cancer

    OpenAIRE

    Alibek, Kenneth; Kakpenova, Ainur; Mussabekova, Assel; Sypabekova, Marzhan; Karatayeva, Nargis

    2013-01-01

    The most common cancer worldwide among women is breast cancer. The initiation, promotion, and progression of this cancer result from both internal and external factors. The International Agency for Research on Cancer stated that 18-20% of cancers are linked to infection, and the list of definite, probable, and possible carcinogenic agents is growing each year. Among them, biological carcinogens play a significant role. In this review, data covering infection-associated breast and lung cancers...

  10. Development of three-dimensional radiotherapy techniques in breast cancer

    Science.gov (United States)

    Coles, Charlotte E.

    Radiotherapy following conservation surgery decreases local relapse and death from breast cancer. Currently, the challenge is to minimise the morbidity caused by this treatment without losing efficacy. Despite many advances in radiation techniques in other sites of the body, the majority of breast cancer patients are still planned and treated using 2-dimensional simple radiotherapy techniques. In addition, breast irradiation currently consumes 30% of the UK's radiotherapy workload. Therefore, any change to more complex treatment should be of proven benefit. The primary objective of this research is to develop and evaluate novel radiotherapy techniques to decrease irradiation of normal structures and improve localisation of the tumour bed. I have developed a forward-planned intensity modulated (IMRT) breast radiotherapy technique, which has shown improved dosimetry results compared to standard breast radiotherapy. Subsequently, I have developed and implemented a phase III randomised controlled breast IMRT trial. This National Cancer Research Network adopted trial will answer an important question regarding the clinical benefit of breast IMRT. It will provide DNA samples linked with high quality clinical outcome data, for a national translational radiogenomics study investigating variation in normal tissue toxicity. Thus, patients with significant late normal tissue side effects despite good dose homogeneity will provide the best model for finding differences due to underlying genetics. I evaluated a novel technique using high definition free-hand 3-dimensional (3D) ultrasound in a phantom study, and the results suggested that this is an accurate and reproducible method for tumour bed localisation. I then compared recognised methods of tumour bed localisation with the 3D ultrasound method in a clinical study. The 3D ultrasound technique appeared to accurately represent the shape and spatial position of the tumour cavity. This tumour bed localisation research

  11. The National Cancer Institute's PREVENT Cancer Preclinical Drug Development Program: overview, current projects, animal models, agent development strategies, and molecular targets.

    Science.gov (United States)

    Shoemaker, Robert H; Suen, Chen S; Holmes, Cathy A; Fay, Judith R; Steele, Vernon E

    2016-02-01

    The PREVENT Cancer Preclinical Drug Development Program (PREVENT) is a National Cancer Institute, Division of Cancer Prevention (NCI, DCP)-supported program whose primary goal is to bring new cancer preventive interventions (small molecules and vaccines) and biomarkers through preclinical development towards clinical trials by creating partnerships between the public sector (eg, academia, industry) and DCP. PREVENT has a formalized structure for moving interventions forward in the prevention pipeline using a stage-gate process with go/no go decision points along the critical path for development. This review describes the structure of the program, its focus areas, and provides examples of projects currently in the pipeline. PMID:26970137

  12. Funding Opportunities Available for Innovative SBIR Development - Office of Cancer Clinical Proteomics Research

    Science.gov (United States)

    Does your small business need early-stage financing to take its cancer research to the next level? The National Cancer Institute Small Business Innovation Research (NCI SBIR) Development Center has released $5 million for new contract funding opportunities to support cancer research and technology development in key emerging areas of need.

  13. The Role of Cathelicidin LL-37 in Cancer Development.

    Science.gov (United States)

    Piktel, Ewelina; Niemirowicz, Katarzyna; Wnorowska, Urszula; Wątek, Marzena; Wollny, Tomasz; Głuszek, Katarzyna; Góźdź, Stanisław; Levental, Ilya; Bucki, Robert

    2016-02-01

    LL-37 is a C-terminal peptide proteolytically released from 18 kDa human cathelicidin protein (hCAP18). Chronic infections, inflammation, tissue injury and tissue regeneration are all linked with neoplastic growth, and involve LL-37 antibacterial and immunomodulatory functions. Such a link points to the possible involvement of LL-37 peptide in carcinogenesis. An increasing amount of evidence suggests that LL-37 can have two different and contradictory effects--promotion or inhibition of tumor growth. The mechanisms are tissue-specific, complex, and depend mostly on the ability of LL-37 to act as a ligand for different membrane receptors whose expression varies on different cancer cells. Overexpression of LL-37 was found to promote development and progression of ovarian, lung and breast cancers, and to suppress tumorigenesis in colon and gastric cancer. This review explores and summarizes the current views on how LL-37 contributes to immunity, pathophysiology and cell signaling involved in malignant tumor growth. PMID:26395996

  14. TRASH TO TREASURE: CONVERTING COLD WAR LEGACY WASTE INTO WEAPONS AGAINST CANCER

    International Nuclear Information System (INIS)

    As part of its commitment to clean up Cold War legacy sites, the U.S. Department of Energy (DOE) has initiated an exciting and unique project to dispose of its inventory of uranium-233 (233U) stored at Oak Ridge National Laboratory (ORNL), and extract isotopes that show great promise in the treatment of deadly cancers. In addition to increasing the supply of potentially useful medical isotopes, the project will rid DOE of a nuclear concern and cut surveillance and security costs. For more than 30 years, DOE's ORNL has stored over 1,200 containers of fissile 233U, originally produced for several defense-related projects, including a pilot study that looked at using 233U as a commercial reactor fuel. This uranium, designated as special nuclear material, requires expensive security, safety, and environmental controls. It has been stored at an ORNL facility, Building 3019A, that dates back to the Manhattan Project. Down-blending the material to a safer form, rather than continuing to store it, will eliminate a $15 million a year financial liability for the DOE and increase the supply of medical isotopes by 5,700 percent. During the down-blending process, thorium-229 (229Th) will be extracted. The thorium will then be used to extract actinium-225 (225Ac), which will ultimately supply its progeny, bismuth-213 (213Bi), for on-going cancer research. The research includes Phase II clinical trials for the treatment of acute myelogenous leukemia at Sloan-Kettering Memorial Cancer Center in New York, as well as other serious cancers of the lungs, pancreas, and kidneys using a technique known as alpha-particle radioimmunotherapy. Alpha-particle radioimmunotherapy is based on the emission of alpha particles by radionuclides. 213Bi is attached to a monoclonal antibody that targets specific cells. The bismuth then delivers a high-powered but short-range radiation dose, effectively killing the cancerous cells but sparing the surrounding tissue. Production of the actinium and

  15. TRASH TO TREASURE: CONVERTING COLD WAR LEGACY WASTE INTO WEAPONS AGAINST CANCER

    Energy Technology Data Exchange (ETDEWEB)

    Nicholas, R.G.; Lacy, N.H.; Butz, T.R.; Brandon, N.E.

    2004-10-06

    As part of its commitment to clean up Cold War legacy sites, the U.S. Department of Energy (DOE) has initiated an exciting and unique project to dispose of its inventory of uranium-233 (233U) stored at Oak Ridge National Laboratory (ORNL), and extract isotopes that show great promise in the treatment of deadly cancers. In addition to increasing the supply of potentially useful medical isotopes, the project will rid DOE of a nuclear concern and cut surveillance and security costs. For more than 30 years, DOE's ORNL has stored over 1,200 containers of fissile 233U, originally produced for several defense-related projects, including a pilot study that looked at using 233U as a commercial reactor fuel. This uranium, designated as special nuclear material, requires expensive security, safety, and environmental controls. It has been stored at an ORNL facility, Building 3019A, that dates back to the Manhattan Project. Down-blending the material to a safer form, rather than continuing to store it, will eliminate a $15 million a year financial liability for the DOE and increase the supply of medical isotopes by 5,700 percent. During the down-blending process, thorium-229 (229Th) will be extracted. The thorium will then be used to extract actinium-225 (225Ac), which will ultimately supply its progeny, bismuth-213 (213Bi), for on-going cancer research. The research includes Phase II clinical trials for the treatment of acute myelogenous leukemia at Sloan-Kettering Memorial Cancer Center in New York, as well as other serious cancers of the lungs, pancreas, and kidneys using a technique known as alpha-particle radioimmunotherapy. Alpha-particle radioimmunotherapy is based on the emission of alpha particles by radionuclides. 213Bi is attached to a monoclonal antibody that targets specific cells. The bismuth then delivers a high-powered but short-range radiation dose, effectively killing the cancerous cells but sparing the surrounding tissue. Production of the actinium and

  16. The Role of Mesenchymal Stem Cell in Cancer Development

    Directory of Open Access Journals (Sweden)

    Hiroshi eYagi

    2013-11-01

    Full Text Available The role of mesenchymal stem cells (MSCs in cancer development is still controversial. MSCs may promote tumor progression through immune modulation, but other tumor suppressive effects of MSCs have also been described. The discrepancy between these results may arise from issues related to different tissue sources, individual donor variability, and injection timing of MSCs. The expression of critical receptors such as Toll-like receptor (TLR is variable at each time point of treatment, which may also determine the effects of MSCs on tumor progression. However, factors released from malignant cells, as well as surrounding tissues and the vasculature, are still regarded as a black box. Thus, it is still difficult to clarify the specific role of MSCs in cancer development. Whether MSCs support or suppress tumor progression is currently unclear, but it is clear that systemically administered MSCs can be recruited and migrate toward tumors. These findings are important because they can be used as a basis for initiating studies to explore the incorporation of engineered MSCs as novel anti-tumor carriers, for the development of tumor-targeted therapies.

  17. Predominance of CIN versus MSI in the development of rectal cancer at young age

    OpenAIRE

    Baldetorp Bo; Halvarsson Britta; Fernebro Eva; Nilbert Mef

    2002-01-01

    Abstract Background Development of proximal and distal colorectal cancers involve partly different mechanisms associated with the microsatellite instability (MSI) and the chromosomal instability (CIN) pathways. Colorectal cancers in patients under 50 years of age represent about 5% of the total number of tumors and have been associated with an increased frequency of MSI tumors. However, MSI and CIN may play different roles in the development of colon cancer and rectal cancer, and we have spec...

  18. COMBINED EXPERIMENTAL AND MATHEMATICAL APPROACH FOR DEVELOPMENT OF MICROFABRICATION-BASED CANCER MIGRATION ASSAY

    OpenAIRE

    Sarkar, Saheli; Bustard, Bethany L.; Welter, Jean F.; Baskaran, Harihara

    2011-01-01

    Migration of cancer cells is a key determinant of metastasis, which is correlated with poor prognosis in patients. Evidence shows that cancer cell motility is regulated by stromal cell interactions. To quantify the role of homotypic and heterotypic cell-cell interaction on migration, a two-dimensional migration assay has been developed by microfabrication techniques. Two breast cancer cell lines, MDA-MB-231 and MDA-MB-453, were used to develop micropatterns of cancer cells (cell islands) that...

  19. Radioimmunotherapy targeting the extra domain B of fibronectin in C6 rat gliomas: a preliminary study about the therapeutic efficacy of iodine-131-labeled SIP(L19)

    International Nuclear Information System (INIS)

    Despite aggressive treatment protocols, patients suffering from glioblastoma multiforme still experience poor outcome. Therefore, new adjuvant therapeutic options such as radioimmunotherapy (RIT) have been studied and have resulted in significant survival benefit. In this study, we assessed the efficacy of a novel radioimmunotherapeutic approach targeting the extra domain B (EDB) of fibronectin, a marker of angiogenesis, in glioma-bearing rats. Methods: C6 gliomas were induced intracerebrally in Wistar rats. Ten to 11 days later, 220-360 MBq of iodine-131-labeled anti-EDB SIP(L19) ('small immunoprotein') was administered intravenously into nine animals, yielding a radiation dose of 13-21 Gy. Another nine rats served as controls. Then the following parameters were compared: median survival time, tumor size and histology. Results: Histological examination of the tumors revealed typical glioblastoma characteristics. Eleven of 18 rats developed a tumor size bigger than 150 mm3. When these animals were used for survival analysis, median survival did significantly differ between groups [22 days (therapy; n=7) vs. 16 days (control; n=4); P131I-SIP(L19)-RIT showed promising potential in treating C6 gliomas, warranting further studies. However, larger trials with preferentially higher doses are needed to confirm this finding and, potentially, to further increase the efficacy of this treatment

  20. The art of professional development and caring in cancer nursing.

    Science.gov (United States)

    Wengström, Yvonne; Ekedahl, Marieanne

    2006-03-01

    The impetus for this qualitative study was the premise expressed by lay people that nursing terminally ill cancer patients must be depressing and difficult to cope with. Its focus was nurses' stress and coping strategies, both secular and religious. Data was collected using a narrative life-story approach, and then Lazaruz and Folkman's coping theory and Pargament's theory on the psychology of religion were used during the analysis of the data. Several factors were identified, related to the individual and group levels, that influence a nurse's identity and professional development. A person's life orientation was suggested as a first concept for developing a professional paradigm that includes caritas as a main orienting factor. Directed by the nurse's secular and religious orientation, competence develops, making it possible to understand, analyze, manage, and appreciate the significance of the professional work of caring. PMID:16451425

  1. Effect of cetuximab in combination with alpha-radioimmunotherapy in cultured squamous cell carcinomas

    International Nuclear Information System (INIS)

    Aim: The monoclonal antibody cetuximab, targeting the epidermal growth factor receptor (EGFR), is a promising molecular targeting agent to be used in combination with radiation for anticancer therapy. In this study, effects of cetuximab in combination with alpha-emitting radioimmunotherapy (RIT) in a panel of cultured human squamous cell carcinomas (SCCs) were assessed. Methods: SCC cell lines were characterized and treated with cetuximab in combination with anti-CD44v6 RIT using the astatinated chimeric monoclonal antibody U36 (211At-cMAb U36). Effects on 211At-cMAb U36 uptake, internalization and cell proliferation were then assessed in SCC cells. Results: Cetuximab in combination with 211At-cMAb U36 mediated increased growth inhibition compared to RIT or cetuximab alone in two cell lines. However, cetuximab also mediated radioprotective effects compared to RIT alone in two cell lines. The radioprotective effects occurred in the cell lines in which cetuximab clearly inhibited cell growth during radiation exposure. Cetuximab treatment also influenced 211At-cMAb-U36 uptake and internalization, suggesting interactions between CD44v6 and EGFR. Conclusions: Results from this study demonstrate the vast importance of further clarifying the mechanisms of cetuximab and radiation response, and the relationship between EGFR and suitable RIT targets. This is important not only in order to avoid potential radioprotective effects, but also in order to find and utilize potential synergistic effects from these combinations.

  2. Effect of cetuximab in combination with alpha-radioimmunotherapy in cultured squamous cell carcinomas

    Energy Technology Data Exchange (ETDEWEB)

    Nestor, Marika, E-mail: marika.nestor@bms.uu.s [Unit of Otolaryngology and Head and Neck Surgery, Department of Surgical Sciences, Uppsala University, S-751 85 Uppsala (Sweden); Unit of Biomedical Radiation Sciences, Department of Oncology, Radiology and Clinical Immunology, Uppsala University, S-751 85 Uppsala (Sweden); Sundstroem, Magnus [Unit of Molecular Pathology, Department of Genetics and Pathology, Uppsala University (Sweden); Anniko, Matti [Unit of Otolaryngology and Head and Neck Surgery, Department of Surgical Sciences, Uppsala University, S-751 85 Uppsala (Sweden); Tolmachev, Vladimir [Unit of Biomedical Radiation Sciences, Department of Oncology, Radiology and Clinical Immunology, Uppsala University, S-751 85 Uppsala (Sweden)

    2011-01-15

    Aim: The monoclonal antibody cetuximab, targeting the epidermal growth factor receptor (EGFR), is a promising molecular targeting agent to be used in combination with radiation for anticancer therapy. In this study, effects of cetuximab in combination with alpha-emitting radioimmunotherapy (RIT) in a panel of cultured human squamous cell carcinomas (SCCs) were assessed. Methods: SCC cell lines were characterized and treated with cetuximab in combination with anti-CD44v6 RIT using the astatinated chimeric monoclonal antibody U36 ({sup 211}At-cMAb U36). Effects on {sup 211}At-cMAb U36 uptake, internalization and cell proliferation were then assessed in SCC cells. Results: Cetuximab in combination with {sup 211}At-cMAb U36 mediated increased growth inhibition compared to RIT or cetuximab alone in two cell lines. However, cetuximab also mediated radioprotective effects compared to RIT alone in two cell lines. The radioprotective effects occurred in the cell lines in which cetuximab clearly inhibited cell growth during radiation exposure. Cetuximab treatment also influenced {sup 211}At-cMAb-U36 uptake and internalization, suggesting interactions between CD44v6 and EGFR. Conclusions: Results from this study demonstrate the vast importance of further clarifying the mechanisms of cetuximab and radiation response, and the relationship between EGFR and suitable RIT targets. This is important not only in order to avoid potential radioprotective effects, but also in order to find and utilize potential synergistic effects from these combinations.

  3. Radioimmunotherapy in a radiation oncology environment: Building a multi-specialty team

    International Nuclear Information System (INIS)

    Radioimmunotherapy (RIT) is a new branch of radiation medicine in which antibodies specific for tumor-associated antigens are linked to radioactive atoms to provide biologically targeted short-range molecular radiotherapy. Two such biologically targeted radiopharmaceuticals have been approved for commercial use in the last few years. Y-90 ibritumomab tiuxetan (Zevalin) and I-131 tositumomab (Bexxar) both recognize the CD-20 surface antigen found on normal and malignant B cells. Both of these compounds produce impressive clinical results when used in the management of indolent, refractory, and transformed CD-20+ B-cell non-Hodgkin's lymphoma, but the unsealed sources involved in this class of compounds also require new types of patient care coordination and patient/environmental safety procedures. Because these multifunctional compounds are ideally administered through a multi-departmental team approach, the planning process to initiate and direct such a team is quite important. This article reviews some of the key processes that may be necessary to establish a successful clinical RIT team. The manuscript highlights the important roles that Radiation oncology team members may play in this multi-department enterprise

  4. Experimental study of 188Re-BAC5 radioimmunotherapy on nasopharyngeal carcinoma

    International Nuclear Information System (INIS)

    The feasibility of radioimmunotherapy for NPC with 188Re-BAC5, a kind of monoclonal antibody to NPC, was investigated. The 188Re-BAC5 was prepared by direct labeling method and its biological activity was determined. The MTT method was used to determine the inhibition effect of the 188Re-BAC5 on CNE-2 cell line culture, and the destruction effect on CNE-2 multicellular spheroids model was also observed. The control group were 188Re-BSA and 188ReO4-. The biological activity of BAC5 was 1:780000 after purification. The labeling yield of 188Re-BAC5 was above 80%. The immuno-activity of 188Re-BAC5 was 61% ± 15%. The results of MTT showed that the inhibition effect of 188Re-BAC5 group was much stronger than the control group (P188Re-BAC5 had a obvious destruction effect on spheroids, and there was a significant difference between 188Re-BAC5 and the control group. In conclusion, 188Re-BAC5 may serve a possible way in the treatment of NPC in the near future

  5. Developing imaging strategies for castration resistant prostate cancer

    International Nuclear Information System (INIS)

    Recent advances in the understanding of castrate-resistant prostate cancer (CRPC) have lead to a growing number of experimental therapies, many of which are directed against the androgen-receptor (AR) signaling axis. These advances generate the need for reliable molecular imaging biomarkers to non-invasively determine efficacy, and to better guide treatment selection of these promising AR-targeted drugs. Methods. We draw on our own experience, supplemented by review of the current literature, to discuss the systematic development of imaging biomarkers for use in the context of CRPC, with a focus on bone scintigraphy, F-18 fluorodeoxyglucose (FDG)-positron emission tomography (PET) and PET imaging of the AR signaling axis. Results. The roadmap to biomarker development mandates rigorous standardization and analytic validation of an assay before it can be qualified successfully for use in an appropriate clinical context. The Prostate Cancer Working Group 2 (PCWG2) criteria for 'radiographic' progression by bone scintigraphy serve as a paradigm of this process. Implemented by the Prostate Cancer Clinical Trials Consortium (PCCTC), these consensus criteria may ultimately enable the co-development of more potent and versatile molecular imaging biomarkers. Purported to be superior to single-photon bone scanning, the added value of Na18F-PET for imaging of bone metastases is still uncertain. FDG-PET already plays an integral role in the management of many diseases, but requires further evaluation before being qualified in the context of CRPC. PET tracers that probe the AR signaling axis, such as 18F-FDHT and 89Zr-591, are now under development as pharmacodynamic markers, and as markers of efficacy, in tandem with FDG-PET. Semi-automated analysis programs for facilitating PET interpretation may serve as a valuable tool to help navigate the biomarker roadmap. Conclusions. Molecular imaging strategies, particularly those that probe the AR signaling axis, have the potential to

  6. Mechanisms of Cell Killing Response from Low Linear Energy Transfer (LET) Radiation Originating from 177Lu Radioimmunotherapy Targeting Disseminated Intraperitoneal Tumor Xenografts

    Science.gov (United States)

    Yong, Kwon Joong; Milenic, Diane E.; Baidoo, Kwamena E.; Brechbiel, Martin W.

    2016-01-01

    Radiolabeled antibodies (mAbs) provide efficient tools for cancer therapy. The combination of low energy β−-emissions (500 keVmax; 130 keVave) along with a γ-emission for imaging makes 177Lu (T1/2 = 6.7 day) a suitable radionuclide for radioimmunotherapy (RIT) of tumor burdens possibly too large to treat with α-particle radiation. RIT with 177Lu-trastuzumab has proven to be effective for treatment of disseminated HER2 positive peritoneal disease in a pre-clinical model. To elucidate mechanisms originating from this RIT therapy at the molecular level, tumor bearing mice (LS-174T intraperitoneal xenografts) were treated with 177Lu-trastuzumab comparatively to animals treated with a non-specific control, 177Lu-HuIgG, and then to prior published results obtained using 212Pb-trastuzumab, an α-particle RIT agent. 177Lu-trastuzumab induced cell death via DNA double strand breaks (DSB), caspase-3 apoptosis, and interfered with DNA-PK expression, which is associated with the repair of DNA non-homologous end joining damage. This contrasts to prior results, wherein 212Pb-trastuzumab was found to down-regulate RAD51, which is involved with homologous recombination DNA damage repair. 177Lu-trastuzumab therapy was associated with significant chromosomal disruption and up-regulation of genes in the apoptotic process. These results suggest an inhibition of the repair mechanism specific to the type of radiation damage being inflicted by either high or low linear energy transfer radiation. Understanding the mechanisms of action of β−- and α-particle RIT comparatively through an in vivo tumor environment offers real information suitable to enhance combination therapy regimens involving α- and β−-particle RIT for the management of intraperitoneal disease. PMID:27196891

  7. Interleukin-6 - A Key Regulator of Colorectal Cancer Development

    Directory of Open Access Journals (Sweden)

    Maximilian J. Waldner, Sebastian Foersch, Markus F. Neurath

    2012-01-01

    Full Text Available Growing evidence proposes an important role for pro-inflammatory cytokines during tumor development. Several experimental and clinical studies have linked the pleiotropic cytokine interleukin-6 (IL-6 to the pathogenesis of sporadic and inflammation-associated colorectal cancer (CRC. Increased IL-6 expression has been related to advanced stage of disease and decreased survival in CRC patients. According to experimental studies, these effects are mediated through IL-6 trans-signaling promoting tumor cell proliferation and inhibiting apoptosis through gp130 activation on tumor cells with subsequent signaling through Janus kinases (JAKs and signal transducer and activator of transcription 3 (STAT3.During recent years, several therapeutics targeting the IL-6/STAT3 pathway have been developed and pose a promising strategy for the treatment of CRC. This review discusses the molecular mechanisms and possible therapeutic targets involved in IL-6 signaling in CRC.

  8. Role of APC and DNA mismatch repair genes in the development of colorectal cancers

    Directory of Open Access Journals (Sweden)

    Roy Deodutta

    2003-12-01

    Full Text Available Abstract Colorectal cancer is the third most common cause of cancer-related death in both men and women in the western hemisphere. According to the American Cancer Society, an estimated 105,500 new cases of colon cancer with 57,100 deaths will occur in the U.S. in 2003, accounting for about 10% of cancer deaths. Among the colon cancer patients, hereditary risk contributes approximately 20%. The main inherited colorectal cancers are the familial adenomatous polyposis (FAP and the hereditary nonpolyposis colorectal cancers (HNPCC. The FAP and HNPCC are caused due to mutations in the adenomatous polyposis coli (APC and DNA mismatch repair (MMR genes. The focus of this review is to summarize the functions of APC and MMR gene products in the development of colorectal cancers.

  9. Fractionated 131I anti-CEA radioimmunotherapy: effects on xenograft tumour growth and haematological toxicity in mice

    OpenAIRE

    Violet, J A; Dearling, J L J; Green, A. J.; Begent, R H J; Pedley, R B

    2008-01-01

    Dose fractionation has been proposed as a method to improve the therapeutic ratio of radioimmunotherapy (RIT). This study compared a single administration of 7.4 MBq 131I-anti-CEA antibody given on day 1 with the same total activity given as fractionated treatment: 3.7 MBq (days 1 and 3), 2.4 MBq (days 1, 3, and 5) or 1.8 MBq (days 1, 3, 5, and 8). Studies in nude mice, bearing the human colorectal xenograft LS174T, showed that increasing the fractionation significantly reduced the efficacy o...

  10. Standard Operating Procedure for Prospective Individualised Dosimetry for [131]I-rituximab Radioimmunotherapy of Non-Hodgkin's Lymphoma

    OpenAIRE

    Calais, Phillipe J.; Turner, J. Harvey

    2012-01-01

    Radioimmunotherapy (RIT) is an attractive therapy for non-Hodgkin's lymphoma (NHL) as it allows targeted tumor irradiation which provides a cytotoxic effect significantly greater than that of the immune-mediated effects of a non-radioactive, or ‘cold’, antibody alone. Anti-CD20 antibodies such as rituximab are ideal for RIT, as not only is it easily iodinated, but the CD20 antigen is found on more than 95% of B-cell NHL. A standard operating procedure (SOP) has been formulated for personalize...

  11. Developing a nanoparticle test for prostate cancer scoring

    OpenAIRE

    Huo Qun; Litherland Sally A; Sullivan Shannon; Hallquist Hillari; Decker David A; Rivera-Ramirez Inoel

    2012-01-01

    Abstract Background Over-diagnosis and treatment of prostate cancer has been a major problem in prostate cancer care and management. Currently the most relevant prognostic factor to predict a patient's risk of death due to prostate cancer is the Gleason score of the biopsied tissue samples. However, pathological analysis is subjective, and the Gleason score is only a qualitative estimate of the cancer malignancy. Molecular biomarkers and diagnostic tests that can accurately predict prostate t...

  12. Development of a Mouse Model of Menopausal Ovarian Cancer

    OpenAIRE

    Elizabeth R Smith; Ying eWang; Xiang-Xi Mike Xu

    2014-01-01

    Despite significant understanding of the genetic mutations involved in ovarian epithelial cancer and advances in genomic approaches for expression and mutation profiling of tumor tissues, several key questions in ovarian cancer biology remain enigmatic: the mechanism for the well-established impact of reproductive factors on ovarian cancer risk remains obscure; questions of the cell of origin of ovarian cancer continue to be debated; and the precursor lesion, sequence, or events in progressi...

  13. Development of the VCaP Androgen Independent Model of Prostate Cancer

    OpenAIRE

    Loberg, Robert D; St. John, Lauren N; Day, LaShon L.; Neeley, Chris K; Kenneth J. Pienta

    2006-01-01

    Prostate epithelial cell growth is dependent on the presence of androgens and the transition of prostate cancer to an androgen independent phenotype results in a highly aggressive, currently incurable cancer. We have developed a new preclinical model of androgen independent prostate cancer derived from the VCaP prostate cancer epithelial cell line. VCaP cells were subcutaneously implanted and serially passaged in castrated male SCID mice. Androgen independence was confirmed by WST-1 (a tetraz...

  14. Development and evaluation of a support program for prostate cancer survivors in Alaska

    OpenAIRE

    Kelley, Stacy; DeCourtney, Christine; Thorsness, Julia

    2015-01-01

    Background. Prostate cancer survivors in Alaska and elsewhere have unmet support needs. The Men’s Prostate Cancer Survivorship Retreat, or “men’s retreat,” was developed targeting Alaska Native and non-Native men who were survivors of prostate cancer. The program brought together survivors in a supportive environment to discuss and share their experiences.Objective. Despite the proven effectiveness of support groups for improving quality of life for cancer patients, men typically do not parti...

  15. Population-based family studies : Genetic contribution to cancer development and survival?

    OpenAIRE

    Lindström, Linda Sofie

    2008-01-01

    Cancer affects essentially everyone, directly or indirectly. The aim of this thesis was to study the genetic and environmental factors in cancer development and survival. Our studies were based on a record linkage between several Swedish population-based registries, principally the Multi-Generation Register, which records familial relationships, the Swedish Cancer Registry, and the Cause of Death Registry. In summary, the Swedish Family-Cancer database comprised over 11 mill...

  16. RECENT DEVELOPMENTS ON TESTING IN CANCER RISK: A FRACTAL AND STOCHASTIC GEOMETRY

    Directory of Open Access Journals (Sweden)

    M. Stehlík

    2012-01-01

    Full Text Available The aim of this paper is to discuss recent development on testing in cancer risk. Weconsider both area of fractal and stochastic geometry based cancer. We introduce the exactdistributions of the likelihood ratio tests of several recently used tests and discuss their properties.We also show possibility of testing for cancer using some stochastic geometry descriptors. Testsfor some new stochastic models in cancer risk are also given.

  17. Development and Validation of the Assessment of Health Literacy in Breast and Cervical Cancer Screening

    OpenAIRE

    Han, Hae-Ra; Huh, Boyun; Kim, Miyong T.; Kim, Jiyun; Nguyen, Tam

    2014-01-01

    For many people limited health literacy is a major barrier to effective preventive health behavior such as cancer screening, yet a comprehensive health literacy measure that is specific to breast and cervical cancer screening is not readily available. The purpose of this paper is to describe the development and testing of a new instrument to measure health literacy in the context of breast and cervical cancer screening, the Assessment of Health Literacy in Cancer Screening (AHL-C). The AHL-C ...

  18. Clinical trial designs for rare diseases: studies developed and discussed by the International Rare Cancers Initiative.

    OpenAIRE

    Bogaerts, Jan; Sydes, Matthew R; Keat, Nicola; McConnell, Andrea; Benson, Al; Ho, Alan; Roth, Arnaud; Fortpied, Catherine; Eng, Cathy; Peckitt, Clare; Coens, Corneel; Pettaway, Curtis; Arnold, Dirk; Hall, Emma; Marshall, Ernie

    2015-01-01

    Background The past three decades have seen rapid improvements in the diagnosis and treatment of most cancers and the most important contributor has been research. Progress in rare cancers has been slower, not least because of the challenges of undertaking research. Settings The International Rare Cancers Initiative (IRCI) is a partnership which aims to stimulate and facilitate the development of international clinical trials for patients with rare cancers. It is focused on interven...

  19. Mitochondrial Defects And Their Role In Development Of Prostate Cancer

    Directory of Open Access Journals (Sweden)

    Nanuli Kotrikadze

    2012-04-01

    Full Text Available Introduction and Objectives: One of the characteristic changes of tumor formation is accumulation of genetic disorders in mitochondrial and nuclear genome. Mitochondrial disorders, from its side, are responsible for failure of metabolism, apoptosis, cell growth, formation of reactive oxygen species, etc. Overprpoduction of reactive oxygen species (ROS significantly impacts the respiration chain enzymes and entirely the antioxidant system of mitochondria. Finally this may become a favorable condition for normal cells transformation.The purpose of the presented work was to study  the mitochondrial defects and to establish their role in prostate cancer development.Results: Experimental results demonstrate significant increase of the activity of mitochondrial succinate dehydrogenaze (complex II of the malignant epithelial cells of prostate, and slight changes in cytochrome oxydase (complex IV activity. Also significant activation of the antioxidant system (glutathione-dependant system of mitochondria in prostate malignant epithelial cells was revealed.Conclusion: The above mentioned mitochondrial changes (II and IV complexes of respiration chain, activity of the antioxidant system partially demonstrate the alterations in mitochondrial energy metabolism, which from its side, may indicate to resistance of prostate cancer cells and correspondingly to intensification of proliferation processes.

  20. Epigenetic regulation leading to induced pluripotency drives cancer development in vivo

    International Nuclear Information System (INIS)

    Highlights: • Epigenetic regulation of failed reprogramming-associated cancer cells is discussed. • Similarity between pediatric cancer and reprogramming-associated cancer is discussed. • Concept for epigenetic cancer is discussed. - Abstract: Somatic cells can be reprogrammed into induced pluripotent stem cells (iPSCs) by the transient expression of reprogramming factors. During the reprogramming process, somatic cells acquire the ability to undergo unlimited proliferation, which is also an important characteristic of cancer cells, while their underlying DNA sequence remains unchanged. Based on the characteristics shared between pluripotent stem cells and cancer cells, the potential involvement of the factors leading to reprogramming toward pluripotency in cancer development has been discussed. Recent in vivo reprogramming studies provided some clues to understanding the role of reprogramming-related epigenetic regulation in cancer development. It was shown that premature termination of the in vivo reprogramming result in the development of tumors that resemble pediatric cancers. Given that epigenetic modifications play a central role during reprogramming, failed reprogramming-associated cancer development may have provided a proof of concept for epigenetics-driven cancer development in vivo

  1. Epigenetic regulation leading to induced pluripotency drives cancer development in vivo

    Energy Technology Data Exchange (ETDEWEB)

    Ohnishi, Kotaro [Center for iPS Cell Research and Application (CiRA), Kyoto University, Kyoto 606-8507 (Japan); Department of Medicine, Gifu University Graduate School of Medicine, Gifu 501-1194 (Japan); Semi, Katsunori [Center for iPS Cell Research and Application (CiRA), Kyoto University, Kyoto 606-8507 (Japan); Institute for Integrated Cell-Material Sciences (WPI-iCeMS), Kyoto University, Kyoto 606-8507 (Japan); Yamada, Yasuhiro, E-mail: y-yamada@cira.kyoto-u.ac.jp [Center for iPS Cell Research and Application (CiRA), Kyoto University, Kyoto 606-8507 (Japan); Institute for Integrated Cell-Material Sciences (WPI-iCeMS), Kyoto University, Kyoto 606-8507 (Japan)

    2014-12-05

    Highlights: • Epigenetic regulation of failed reprogramming-associated cancer cells is discussed. • Similarity between pediatric cancer and reprogramming-associated cancer is discussed. • Concept for epigenetic cancer is discussed. - Abstract: Somatic cells can be reprogrammed into induced pluripotent stem cells (iPSCs) by the transient expression of reprogramming factors. During the reprogramming process, somatic cells acquire the ability to undergo unlimited proliferation, which is also an important characteristic of cancer cells, while their underlying DNA sequence remains unchanged. Based on the characteristics shared between pluripotent stem cells and cancer cells, the potential involvement of the factors leading to reprogramming toward pluripotency in cancer development has been discussed. Recent in vivo reprogramming studies provided some clues to understanding the role of reprogramming-related epigenetic regulation in cancer development. It was shown that premature termination of the in vivo reprogramming result in the development of tumors that resemble pediatric cancers. Given that epigenetic modifications play a central role during reprogramming, failed reprogramming-associated cancer development may have provided a proof of concept for epigenetics-driven cancer development in vivo.

  2. Estimation of baseline lifetime risk of developed cancer related to radiation exposure in China

    International Nuclear Information System (INIS)

    Objective: To introduce the general international method for estimation of lifetime risk of developed cancer, and to estimate the lifetime risk baseline values of several kinds of cancers related to radiation exposures in China. Methods: The risk estimation was based on the data from Chinese Cancer Registry Annual Report (2010) and China Population and Employment Statistics Yearbook (2009), and made according to the method previously published by National Cancer Institute (NCI) in USA. Results: The lifetime risk of all cancer in China in 2007 was estimated to be 27.77%, that of lung cancer 5.96%, that of breast cancer for female 3.34%, that of all leukemia 0.14%, that of thyroid cancer 0.37%. The lifetime risks of all cancer were estimated to be 32.74% for males and 24.73% for females, and that was 36.47% for urban residents and 26.79% for rural people. Conclusions: The lifetime risk of all cancer for males in 2007 was about 1.25 times as much as that for females. The value of all cancer for urban residents was about 1.35 times as much as that for rural residents. The lifetime risk of developed cancers in 2007 in China is lower than that in the developed countries,such as Japan. (authors)

  3. Cancer incidence and novel therapies developed in Japan

    OpenAIRE

    Masaru Iwasaki

    2012-01-01

    According to the ministry of Health, Labour and welfare of Japan, Cancer has been the leading cause of death in Japan since 1981. [1] As per the data in 2010, in Japan, one in every three deaths was due to cancer. [2] The Japanese Government has introduced so far, three terms of 10 years strategies for Cancer control since 1984 till date. The budget allocated for cancer control in 2009 was 52.5 billion yen in Japan. [3] Lung is the leading site for cancer in both males and females in Japan. ...

  4. Assessment and Development of Microwave Imaging for Breast Cancer Detection

    DEFF Research Database (Denmark)

    Jensen, Peter Damsgaard

    . However, a number of different challenges arise when using data from multiple frequencies for imaging of biological targets. The performance of a nonlinear microwave tomography algorithm is tested using simulated data from anatomically realistic breast phantoms. These tests include several different......At the Technical University of Denmark (DTU), a 3D tomographic microwave imaging system is currently being developed with the aim of using nonlinear microwave imaging for breast-cancer detection. The imaging algorithm used in the system is based on an iterative Newton-type scheme. In this algorithm...... algorithm used in the microwave tomographic imaging system is presented. Non-linear microwave tomographic imaging of the breast is a challenging computational problem. The breast is heterogeneous and contains several high-contrast and lossy regions, resulting in large differences in the measured signal...

  5. Cancer Treatment-Related Cardiotoxicity: Understanding the Current State of Knowledge and Developing Future Research Priorities

    Science.gov (United States)

    Cancer Treatment-Related Cardiotoxicity: Understanding the Current State of Knowledge and Developing Future Research Priorities, a 2013 workshop sponsored by the Epidemiology and Genomics Research Program.

  6. Alpha radioimmunotherapy of multiple myeloma: study of feasibility of ex vivo medullary purge

    International Nuclear Information System (INIS)

    The efficiency of the radioimmunotherapy (RIT) using beta emitters has been clinically proved in treatments of refractory forms of lymphoma. The alpha-emitting radioelements of short half-life are also good potential candidates for RIT, applicable to tumor targets accessible rapidly to the molecules of the radio-immuno-conjugates of size compatible with the short range of alpha particles (50 to 80 μm). The goal of this study is to demonstrate the feasibility of such an approach on a model of myeloma multiply targeted by specific antibodies (B-B4) coupled to bismuth-213 with a chelating agent (benzyl-DTPA). The efficiency of the alpha RIT was evaluated in vitro by means of different techniques analyzing the cellular mortality (the method of limited dilution), the effects on DNA (the testing of micro-nuclei), the analysis of radio-induced apoptosis (the test with acridine orange) and finally the study of non-specific irradiation on population of cells of hematopoietic system un-recognized by the B-B4 benzyl-DTPA) immuno-conjugate. The first results have shown besides the technical feasibility of the project a strong dose dependent cellular mortality with a survival falling rapidly from 28% to around 1 o/oo for a single doubling of the dose from 14.8 kBq / 105 cells (0.4 μCi) to 29.6 kBq/105 cells (0.8 μCi). The cellular mortality was total at 300 kBq/105 cells (8 μCi). The cells in an apoptosis state were evidenced at rates up to 40% for a dose of 7.4 kBq/105 cells (0.2 μ Ci). New experiments will permit confirming these first results and determining the irradiation range having in view a utilization in protocols of purging of the myeloma cells on pockets obtained after plasmaphereses

  7. Radioimmunotherapy for Lymphoma%淋巴瘤的放射免疫治疗

    Institute of Scientific and Technical Information of China (English)

    卢霞; 王荣福

    2009-01-01

    恶性淋巴瘤是欧美国家常见的造血系统恶性肿瘤,其发病率逐年上升.大多数滤泡型非霍奇金淋巴瘤多为慢性、难治性恶性肿瘤,易复发,治疗困难.现有的治疗方案包括化疗、放疗、单克隆抗体介导的免疫治疗、放射免疫治疗及造血干细胞移植治疗.放射性核素131I和90 Y标记的单克隆抗体的放射免疫治疗的疗效有待于进一步研究.%Non-Hodgkin's lymphoma (NHL) is the most common hematological malignancy in the United States with a rapidly increasing incidence. Most follicular NHL is indolent but incurable, Most patients with follicular NHL who transform to an aggressive NHL are very difficult to treat successfully. Treatment options have included chemotherapy, radiation, immunotherapy with monoclonal antibodies, alone or in combination, and hematopoietic stem cell transplantation. The efficacy of monoclonal antibodies is augmented when they are combined with a radioisotope like iodine-131 or yttrium-90. There have been a number of studies done in recent years studying the efficacy of this form of therapy, i.e., radioimmunotherapy (RIT) in patients with NHL. This review attempts to integrate the information from the various clinical trials done using RIT in patients with relapsed/refractory or newly diagnosed NHL.

  8. Evaluation of a new biotin-DOTA conjugate for pretargeted antibody-guided radioimmunotherapy (PAGRIT registered)

    International Nuclear Information System (INIS)

    A novel biotin-DOTA conjugate (r-BHD: reduced biotinamidohexylamine-DOTA) was investigated in order to provide an efficient pretargeted antibody-guided radioimmunotherapy (PAGRIT registered) application. Preclinical and clinical results are described. 90Y and 177Lu were used to label r-BHD. The effect of pH and a wide range of specific activities were studied. Radiolabelled r-BHD was tested for affinity towards avidin and for stability in saline or in human serum with and without ascorbic acid. Pharmacokinetic data were collected and organ biodistribution evaluated in a tumour-bearing pretargeted animal model. A pilot study was performed in a metastatic melanoma patient and dosimetry was estimated. High radiochemical purity (>99%) was routinely achieved with 90Y or 177Lu in sodium acetate buffer (1.0 M, pH 5.0) at a specific activity of 2.6 MBq/nmol. Both 90Y- and 177Lu-r-BHD were also prepared at higher specific activities. Radiolabelled r-BHD was stable up to 96 h in human serum and saline with the addition of ascorbic acid. The structural modifications proposed for the r-BHD stabilised it against enzymatic degradation while retaining high binding affinity for avidin. Renal clearance appeared to be the main route of excretion in animals, and high tumour uptake was observed in the pretargeted animals. The patient study showed a total body clearance of ∝85% in 24 h, with a kidney absorbed dose of 1.5 mGy/MBq. Tumour uptake was rapid and the calculated dose to a 10-mm tumour lesion was ∝12 mGy/MBq. These results indicate that the new biotin-DOTA conjugate may be a suitable candidate for pretargeting trials. (orig.)

  9. Development of novel magnetic nanoparticles for hyperthermia cancer therapy

    Science.gov (United States)

    Cassim, Shiraz M.; Giustini, Andrew J.; Baker, Ian; Hoopes, P. Jack

    2011-03-01

    Advances in magnetic nanoparticle hyperthermia are opening new doors in cancer therapy. As a standalone or adjuvant therapy this new modality has the opportunity significantly advance thermal medicine. Major advantages of using magnetic magnetite (Fe3O4) nanoparticles are their highly localized power deposition and the fact that the alternating magnetic fields (AMF) used to excite them can penetrate deeply into the body without harmful effect. One limitation, however, which hinders the technology, is the problem of inductive heating of normal tissue by the AMF if the frequency and fields strength are not appropriately matched to the tissue. Restricting AMF amplitude and frequency limits the heat dose which can be selectively applied to cancerous tissue via the magnetic nanoparticle, thus lowering therapeutic effect. In an effort to address this problem, particles with optimized magnetic properties must be developed. Using particles with higher saturation magnetizations and coercivity will enhance hysteresis heating increasing particle power density at milder AMF strengths and frequencies. In this study we used oil in water microemulsions to develop nanoparticles with zero-valent Fe cores and magnetite shells. The superior magnetic properties of zero-valent Fe give these particles the potential for improved SAR over pure magnetite particles. Silane and subsequently dextran have been attached to the particle surface in order to provide a biocompatible surfactant coating. The heating capability of the particles was tested in-vivo using a mouse tumor model. Although we determined that the final stage of synthesis, purification of the dextran coated particles, permits significant corrosion/oxidation of the iron core to hematite, the particles can effectively heat tumor tissue. Improving the purification procedure will allow the generation Fe/Fe3O4 with superior SAR values.

  10. Inconvenient truth: cancer biomarker development by using proteomics.

    Science.gov (United States)

    Kondo, Tadashi

    2014-05-01

    A biomarker is a crucial tool for measuring the progress of disease and the effects of treatment for better clinical outcomes in cancer patients. Diagnostic, predictive, and prognostic biomarkers are required in various clinical settings. The proteome, a functional translation of the genome, is considered a rich source of biomarkers; therefore, sizable time and funding have been spent in proteomics to develop biomarkers. Although significant progress has been made in technologies toward comprehensive protein expression profiling, and many biomarker candidates published, none of the reported biomarkers have proven to be beneficial for cancer patients. The present deceleration in biomarker research can be attributed to technical limitations. Additional efforts are required to further technical progress; however, there are many examples demonstrating that problems in biomarker research are not so much with the technology but in the study design. In the study of biomarkers for early diagnosis, candidates are screened and validated by comparing cases and controls of similar sample size, and the low prevalence of disease is often ignored. Although it is reasonable to take advantage of multiple rather than single biomarkers when studying diverse disease mechanisms, the annotation of individual components of reported multiple biomarkers does not often explain the variety of molecular events underlying the clinical observations. In tissue biomarker studies, the heterogeneity of disease tissues and pathological observations are often not considered, and tissues are homogenized as a whole for protein extraction. In addition to the challenge of technical limitations, the fundamental aspects of biomarker development in a disease study need to be addressed. This article is part of a Special Issue entitled: Biomarkers: A Proteomic Challenge. PMID:23896458

  11. Cancer screening: Should cancer screening be essential component of primary health care in developing countries?

    OpenAIRE

    Saurabh Bobdey; Ganesh Balasubramanium; Abhinendra Kumar; Aanchal Jain

    2015-01-01

    Background: Cancer is a fatal disease and is on the rise across the globe. In India, breast, cervix and the oral cavity are the leading cancer sites, but, unfortunately, in-spite of availability of screening tools, there is no organized cancer screening program in India. The main objective of this study was to review the performance of various cancer screening modalities in a resource poor setting. Methods: MEDLINE and web of science electronic database was searched from January 1990 to D...

  12. Clinical trials of cancer screening in the developing world and their impact on cancer healthcare.

    Science.gov (United States)

    Sankaranarayanan, R; Sauvaget, C; Ramadas, K; Ngoma, T; Teguete, I; Muwonge, R; Naud, P; Nessa, A; Kuhaprema, T; Qiao, Y

    2011-11-01

    Several research and training initiatives were organized by the International Agency for Research on Cancer (IARC) in collaboration with national institutions in countries such as Angola, Brazil, Burkina Faso, China, Republic of Congo, Guinea, India, Mali, Mauritania, Nepal, Niger, Peru, Tanzania and Thailand among others, to address feasible and effective means of early detection and prevention of cervical, breast and oral cancers. The impact of these activities, that involved over 600 000 participants and more than 1200 healthcare personnel trained on strengthening the local health services in terms of infrastructure, human resources and service delivery aspects in host countries and other regions, is addressed here. These studies, inbuilt in appropriate health services platforms, have resulted in the development and sustenance of several continuing point of care services of screening and treatment in most host countries, particularly in sub-Saharan Africa, and have catalysed regional early detection programmes in India, China and Thailand. The IARC collaborative studies have evolved into major focal points of training and extending services in many countries. The large evidence base, resulting from ours and other studies is likely, in due course, to facilitate much wider scaling up of screening and treatment services through organised programmes. PMID:22039141

  13. Cancer Research UK Centre for Drug Development: translating 21st-century science into the cancer medicines of tomorrow.

    Science.gov (United States)

    Ritchie, James W A; Williams, Robert J

    2015-08-01

    The Cancer Research UK Centre (CRUK) for Drug Development (CDD) can trace its origins back to the Cancer Research Campaign Phase I/II Committee (created in 1980) and to date has tested over 120 potential cancer medicines in early-phase clinical trials. Five drugs are now registered, providing benefit to thousands of patients with cancer as part of their routine standard of care. In recent years, the CDD has established several different business and operating models that provide it with access to the pipelines of pharmaceutical and biotechnology companies. This has enabled potential new treatments to be taken into clinical development that might have otherwise languished on companies' shelves and has increased the number of drug combinations being explored in early-phase clinical trials. PMID:25794601

  14. [Development of Precision Medicine in the Surgical Treatment of Lung Cancer].

    Science.gov (United States)

    Tan, Fengwei; Li, Ning; Gao, Shugeng; He, Jie

    2016-06-20

    Precision medicine is to developing the most appropriate individualized treatment for each patient based on the macro to the micro level of individual differences. Genomic, proteomics, metabolomics data, and other big data analysis methods are the essence of precision medicine. Precision medicine brings the hope to overcome cancer. Among all kinds of tumors, lung cancer is the biggest threat to human. This paper reviewed the development of precision medicine in the surgical treatment of lung cancer. PMID:27335287

  15. Exosomes in development, metastasis and drug resistance of breast cancer

    OpenAIRE

    Yu, Dan-Dan; Wu, Ying; Shen, Hong-yu; Lv, Meng-meng; Chen, Wei-Xian; Zhang, Xiao-Hui; Zhong, Shan-liang; Tang, Jin-Hai; Zhao, Jian-Hua

    2015-01-01

    Transport through the cell membrane can be divided into active, passive and vesicular types (exosomes). Exosomes are nano-sized vesicles released by a variety of cells. Emerging evidence shows that exosomes play a critical role in cancers. Exosomes mediate communication between stroma and cancer cells through the transfer of nucleic acid and proteins. It is demonstrated that the contents and the quantity of exosomes will change after occurrence of cancers. Over the last decade, growing attent...

  16. Personalizing medicine for metastatic colorectal cancer: Current developments

    OpenAIRE

    Marques, Andrea Marin; Turner, Alice; de Mello, Ramon Andrade

    2014-01-01

    Metastatic colorectal cancer (mCRC) is still one of the tumor types with the highest incidence and mortality. In 2012, colorectal cancer was the second most prevalence cancer among males (9%) and the third among females (8%). In this disease, early diagnosis is important to improve treatment outcomes. However, at the time of diagnosis, about one quarter of patients already have metastases, and overall survival of these patients at 5-years survival is very low. Because of these poor statistics...

  17. Behavioral stress accelerates prostate cancer development in mice

    OpenAIRE

    Hassan, Sazzad; Karpova, Yelena; Baiz, Daniele; Yancey, Dana; Pullikuth, Ashok; Flores, Anabel; Register, Thomas; Cline, J. Mark; D’Agostino, Ralph; Danial, Nika; Datta, Sandeep Robert; Kulik, George

    2013-01-01

    Prostate cancer patients have increased levels of stress and anxiety. Conversely, men who take beta blockers, which interfere with signaling from the stress hormones adrenaline and noradrenaline, have a lower incidence of prostate cancer; however, the mechanisms underlying stress–prostate cancer interactions are unknown. Here, we report that stress promotes prostate carcinogenesis in mice in an adrenaline-dependent manner. Behavioral stress inhibited apoptosis and delayed prostate tumor invol...

  18. Adjuvant Therapy of Colon Cancer: Current Status and Future Developments

    OpenAIRE

    Morse, Michael A.

    2005-01-01

    Options for the adjuvant therapy of resected stage III colon cancer have expanded beyond the previously well-accepted standard of 5-fluorouracil (5-FU) combined with leucovorin. The Xeloda in Adjuvant Colon Cancer Therapy (X-ACT) study confirmed that capecitabine (Xeloda) is at least as effective and is less toxic than a bolus 5-FU and leucovorin regimen for patients with stage III colon cancer. This study, in addition to National Surgical Adjuvant Breast and Bowel Project (NSABP) C-06, which...

  19. Genetic Evidence for XPC-KRAS Interactions During Lung Cancer Development.

    Science.gov (United States)

    Zhang, Xiaoli; He, Nonggao; Gu, Dongsheng; Wickliffe, Jeff; Salazar, James; Boldogh, Istavan; Xie, Jingwu

    2015-10-20

    Lung cancer causes more deaths than breast, colorectal and prostate cancers combined. Despite major advances in targeted therapy in a subset of lung adenocarcinomas, the overall 5-year survival rate for lung cancer worldwide has not significantly changed for the last few decades. DNA repair deficiency is known to contribute to lung cancer development. In fact, human polymorphisms in DNA repair genes such as xeroderma pigmentosum group C (XPC) are highly associated with lung cancer incidence. However, the direct genetic evidence for the role of XPC for lung cancer development is still lacking. Mutations of the Kirsten rat sarcoma viral oncogene homolog (Kras) or its downstream effector genes occur in almost all lung cancer cells, and there are a number of mouse models for lung cancer with these mutations. Using activated Kras, Kras(LA1), as a driver for lung cancer development in mice, we showed for the first time that mice with Kras(LA1) and Xpc knockout had worst outcomes in lung cancer development, and this phenotype was associated with accumulated DNA damage. Using cultured cells, we demonstrated that induced expression of oncogenic KRAS(G12V) led to increased levels of reactive oxygen species (ROS) as well as DNA damage, and both can be suppressed by anti-oxidants. Our results suggest that XPC may help repair DNA damage caused by KRAS-mediated production of ROS. PMID:26554912

  20. Development of 177Lu-DOTA-anti-CD20 for radioimmunotherapy

    International Nuclear Information System (INIS)

    Rituximab was successively labeled with 177Lu-lutetium chloride. 177Lu chloride was obtained by thermal neutron flux (4 x 1013 n cm-2 s-1) of natural Lu2O3 sample with a specific activity of 2.6-3 GBq/mg. The macrocyclic bifunctional chelating agent, N-succinimidyl-1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA-NHS) was prepared at 25 deg C using DOTA, N-hydroxy succinimide (NHS) in CH2Cl2. DOTA-rituximab was obtained by the addition of 1 mL of a rituximab pharmaceutical solution (5 mg/mL, in phosphate buffer, pH 7.8) to a glass tube pre-coated with DOTA-NHS (0.01-0.1 mg) at 25 deg C with continuous mild stirring for 15 h. Radiolabeling was performed at 37 deg C in 24 h. Radio-thin layer chromatography showed an overall radiochemical purity of >98% at optimized conditions (specific activity = 444 MBq/mg, labeling efficacy; 82%). The final isotonic 177Lu-DOTA-rituximab complex was checked by gel electrophoresis for structure integrity control. Radio-TLC was performed to ensure that only one species was present after filtration through a 0.22 μm filter. Preliminary biodistribution studies in normal rats were carried out to determine complex distribution of the radioimmunoconjugate up to 168 h. The biodistribution data were in accordance with other antiCD20 radioimmunoconjugates already reported. (author)

  1. Gastric cancer development after the successful eradication of Helicobacter pylori.

    Science.gov (United States)

    Uno, Kaname; Iijima, Katsunori; Shimosegawa, Tooru

    2016-03-15

    Gastric cancer (GC) develops as a result of inflammation-associated carcinogenesis due to Helicobacter pylori (H. pylori) infection and subsequent defects in genetic/epigenetic events. Although the indication for eradication therapy has become widespread, clinical studies have revealed its limited effects in decreasing the incidence of GC. Moreover, research on biopsy specimens obtained by conventional endoscopy has demonstrated the feasibility of the restoration of some genetic/epigenetic alterations in the gastric mucosa. Practically, the number of sporadic cases of primary/metachronous GC that emerge after successful eradication has increased, while on-going guidelines recommend eradication therapy for patients with chronic gastritis and those with background mucosa after endoscopic resection for GC. Accordingly, regular surveillance of numerous individuals who have received eradication therapy is recommended despite the lack of biomarkers. Recently, the focus has been on functional reversibility after successful eradication as another cue to elucidate the mechanisms of restoration as well as those of carcinogenesis in the gastric mucosa after H. pylori eradication. We demonstrated that Congo-red chromoendoscopy enabled the identification of the multi-focal distribution of functionally irreversible mucosa compared with that of restored mucosa after successful eradication in individuals at extremely high risk for GC. Further research that uses functional imaging may provide new insights into the mechanisms of regeneration and carcinogenesis in the gastric mucosa post-eradication and may allow for the development of useful biomarkers. PMID:26989462

  2. Developing National Cancer Registration in Developing Countries- Case Study of the Nigerian National System of Cancer Registries

    Directory of Open Access Journals (Sweden)

    Elima E Jedy-Agba

    2015-07-01

    Full Text Available The epidemiologic transition in sub-Saharan Africa (SSA has given rise to a concomitant increase in the incidence of non-communicable diseases including cancers. Worldwide, cancer registries have been shown to be critical for the determination of cancer burden, conduct of research, and in the planning and implementation of cancer control measures. Cancer registration though vital is often neglected in SSA owing to competing demands for resources for healthcare.We report the implementation of a system for representative nation-wide cancer registration in Nigeria - the Nigerian National System of Cancer Registries (NSCR. The NSCR coordinates the activities of cancer registries in Nigeria, strengthens existing registries, establishes new registries, complies and analyses data, and makes these freely available to researchers and policy makers. We highlight the key challenges encountered in implementing this strategy and how they were overcome. This report serves as a guide for other low and middle income countries (LMIC wishing to expand cancer registration coverage in their countries and highlights the training, mentoring, scientific and logistic support, and advocacy that are crucial to sustaining cancer registration programs in LMIC

  3. Radio-immunoconjugated, Dox-loaded, surface-modified superparamagnetic iron oxide nanoparticles (SPIONs) as a bioprobe for breast cancer tumor theranostics

    International Nuclear Information System (INIS)

    In this research, we develop dual modality molecular imaging and also radio-immunotherapy (RIT) bioprobes, in the form of modified superparamagnetic iron oxide nanoparticles (SPIONs) conjugated to radiolabeled antibodies, for PET and MRI of HER2 expressing cancers as well as a PH sensitive drug carrier by embedded an anticancer agent for cancer therapeutic applications. The bioprobes were developed by conjugating 64Cu labeled trastuzumab (herceptin) and rituximab (Anti CD-20) antibodies to modified SPIONs. The SPIONs were modified with carboxymethyl chitosan and functionalized with acrylic acid (AA). Also, with the purpose of identifying more effective bifunctional chelator (BFC), we compared the properties of novel BFC, p-NO2-Bn-PCTA with the commonly used DOTA-NHS for radio-immunoconjugate preparations. Moreover, a chemotherapy drug, doxorubicin, was then loaded onto engineered nanoparticles for targeted intracellular drug delivery and selective cancer cell killing. Resulting radio-immunoconjugated-SPIONs were evaluated for molecular imaging and effective targeting of the HER2+ receptors in SKBR3 cell lines and breast tumor bearing Balb/C mice. Therefore, our biocompatible SPIONs could serve as a promising multifunctional theranostics nanoplatform in dual modality imaging guided RIT of HER2 overexpressing cancer applicable to drug delivery and controlled drug release for trigger both intrinsic and extrinsic pathways of apoptosis. (author)

  4. Radiobioconjugate targetting in cancer in developing countries: Regulatory issues

    International Nuclear Information System (INIS)

    Full text: The radiobioharmaceuticals for targeting cancers include radiolabelled monoclonal antibodies, peptides, anti sense nucleotides as well as intermediate molecules in pretargetting strategies. Scientists in developing countries that wish to use these agents whether for diagnosis or for therapy face formidable barriers, and this communication proposes pragmatic strategies to overcome these hurdles. Firstly such agents prior to radiolabellling have to be prepared according to Good Manufacturing Practice standards,suggested criteria for which have been formulated. Secondly, for therapy use, since centralized distribution of a high dose labeled radiopharmaceutical such as an Iodine labeled antibody is not available from a source in the country or region, and may not be feasible for logistic and economic reasons, compounded by the distances between the radiopharmaceutical manufacturing centers and the user hospitals,high dose radiolabelling has to be undertaken in house in the user centre. This necessitates understanding of the hazards especially with volatile isotopes such as radioiodine, and adequate precautions to limit these. For the addition of radioiodine remote controlled pipetting has been proposed. Another strategy is the use of resins to mop up excess radiolabel. With other radiolabels such as Rhenium, Lutecium and Gold, the problem of volatility is avoided but obtaining these at adequate specific activity and purity is sometimes difficult resulting in the need for concentration techniques. Rhenium-188 from Tungsten generators is superior to the reactor produced Rhenium-186/188 mixtures. This problem does not exist as regards diagnostic targeting where Technetium-99m is adequate and is available sterile from column generators. The use of pretargetting strategies with the final agent being a radiolabelled biotin or radiolabelled chelate may enable centralized preparation and distribution of these. Thirdly the availability of biological agents is

  5. Initial experience with locoregional radioimmunotherapy using 131I-labelled monoclonal antibodies against tenascin (BC-4) for treatment of glioma (WHO III and IV)

    International Nuclear Information System (INIS)

    Aim: None of the established treatments (surgery, radiotherapy, chemotherapy) for malignant glioma has improved its very poor prognosis. Adjuvant locoregional radioimmunotherapy (RIT) represents a new therapeutic approach. We present our initial experience with this therapeutic tool with respect to adverse effects, biokinetics and clinical follow-up. Methods: Following surgery and radiotherapy, 12 patients with glioma (4, WHO stage III; 8, WHO stage IV) underwent 1-5 RIT-cycles (average dose 1100 MBq 131labelled monoclonal BC-4 antibodies) at six week intervals. Follow-up included serial FDG-PET and MRI investigations. Evaluation of biokinetics included whole body scans, together with analysis of blood, urine and fluid from the tumor cavity. Results: Following RIT, four patients experienced temporary seizures, which, in one case, were associated with temporary aphasia. Eight patients developed HAMA (human anti-mouse anti-bodies) during follow-up. Mean biologic half-life of the radiopharmaceutical in the resection cavity was 3.9 d (range: 1.0-10.2 d) and remained stable intraindividually during further RIT-cycles. The antibody/radionuclide conjugate remain stable in the tumor cavity for at least 5 d. Median survival presently stands at 18.5 months compared to 9.7 months in a historical patient group (n=89) undergoing conventional therapeutic strategies. Five patients show no signs of recurrence. In three patients with post-surgical evidence of residual tumor, one patient showed partial remission, one stable disease, and one progressive disease during RIT. Four patients without evidence of residual tumor mass at the beginning of RIT developed recurrence during therapy. Conclusions: Initial experience demonstrates that locoregional RIT is a well tolerated treatment modality that may represent a promising new approach in the management of patients with malignant glioma. Advantages of local application include passage of the blood-brain barrier, high concentration of

  6. New methods in mammary gland development and cancer: proteomics, epigenetics, symmetric division and metastasis

    OpenAIRE

    Bentires-Alj, Mohamed; GLUKHOVA, Marina; Hynes, Nancy; Vivanco, Maria dM

    2012-01-01

    The European Network for Breast Development and Cancer (ENBDC) meeting on 'Methods in Mammary Gland Development and Cancer' has become an annual international rendezvous for scientists with interests in the normal and neoplastic breast. The fourth meeting in this series, held in April in Weggis, Switzerland, focused on proteomics, epigenetics, symmetric division, and metastasis.

  7. 78 FR 40485 - Lung Cancer Patient-Focused Drug Development; Extension of Comment Period

    Science.gov (United States)

    2013-07-05

    ... lung cancer patient-focused drug development. In the Federal Register of June 5, 2013 (78 FR 33581... HUMAN SERVICES Food and Drug Administration Lung Cancer Patient-Focused Drug Development; Extension of... In the Federal Register of June 5, 2013 (78 FR 33581), FDA announced an opportunity for...

  8. MITOCHONDRIA: INSIGHT TARGET OF DRUG DEVELOPMENT IN CANCER CELLS

    OpenAIRE

    Md. Ataur Rahman

    2012-01-01

    Mitochondria are involved in different physiological and pathological processes that are crucial for tumor cell physiology, growth and survival and its dysfunction leads to many human abnormalities, including cardiovascular diseases, neurodegenerative diseases, autoimmune disorders and cancer. The present review is focused on the different experimental and therapeutic cancer strategies addressed to either target mitochondria directly, or use mitochondria as mediators of apoptosis, although it...

  9. Radioimmunotherapy with Y-90-epratuzumab in patients with previously treated B-cell lymphoma. A fractionated dose-escalation study

    International Nuclear Information System (INIS)

    Aim: Fractionated RIT may improve outcome by decreasing heterogeneity in absorbed dose and by increasing therapeutic window. The humanised anti-CD22 antibody, Epratuzumab, (Immunomedics, Inc., Morris Plains, NJ) can be given repeatedly with minimal risk of neutralising Ab (HAHA), making fractionated treatment with 90Y-labelled epratuzumab possible. Materials and Methods: Patients with previously treated B-cell lymphoma received increasing number (2-4) of weekly infusions of 90Y-epratuzumab. Patients received either 185 MBq/m2 per infusion (group A), or, if they had a history of high-dose chemotherapy with stem-cell rescue, 92.5 MBq/m2 per infusion (group B). The first infusion included 150 MBq of 111Indium for scintigraphic verification of tumour targeting and dosimetry. 1.5 mg/kg epratuzumab was administered with each infusion. The treatment could be repeated once after 3 m. Results: Of 23 patients, 16 in group A and 6 in group B were evaluable for response. The RR in group A was 62% objective response (OR) and 25% CR/CRu. One patient in group B showed OR. OR was seen in aggressive and indolent lymphoma. Response was also long-lasting and event-free survival of patients showing CR/CRu was 14 to 25+ months. In group A all seven patient, receiving three infusions, showed less than grade 3 platelet and neutrophil toxicity, except for two patients suffering grade 3 neutropenia. Of five patients with 4 weekly infusions there were two patients with dose-limiting haematological toxicity (DLT), both recently treated with high dose cytosar before RIT. With criteria used the maximal tolerated dose was three infusions 185 MBq/m2. In group B no patient suffered DLT and one patient exhibited OR. Seven patients were retreated after 3 months with minor toxicity, but improvement in OR in two cases. No patient has developed HAHA. CD22 expression on tumour cells, as assessed by flow cytometry, is available in 18 of 22 patients. In group A, seven of eight patients with unequivocal

  10. Strategic development on generic anti-cancer drugs Bevacizumab and Erlotinib Hydrochloride for Harbin Pharmaceutical Group

    Institute of Scientific and Technical Information of China (English)

    Cheung Fat Ping

    2011-01-01

    @@ With improved economy, changing life styles, aging population and health care reform, China had a very potential anti-cancer drug market.The patents of popular anti-cancer drugs Avastin and Tarceva would expire in few years.Generic versions of Avastin and Tarceva were Bevacizumab and Erlotinib Hydrochloride respectively.Harbin Pharmaceutical Group was proposed to develop strategically both generic medicines to enter the high-end anti-cancer drug market for targeted cancer therapies.The vital to success of developing the generic drugs were discussed.

  11. DNA damage-centered signaling pathways are effectively activated during low dose-rate Auger radioimmunotherapy

    International Nuclear Information System (INIS)

    Introduction: Low dose-rate radioimmunotherapy (RIT) using 125I-labelled monoclonal antibodies (125I-mAbs) is associated with unexpected high cytotoxicity per Gy. Methods: We investigated whether this hypersensitivity was due to lack of detection of DNA damage by the targeted cells. DNA damage was measured with the alkaline comet assay, gamma-H2AX foci and the micronucleus test in p53−/− and p53+/+ HCT116 cells exposed to increasing activities of internalizing anti-HER1 125I-mAbs or non-internalizing anti-CEA 125I-mAbs. The expression of proteins involved in radiation response and progression of cells through the cycle were determined. Results: Cell hypersensitivity to low absorbed doses of anti-CEA 125I-mAbs was not due to defect in DNA damage detection, since ATM (ataxia telangiectasia mutated gene), gamma-H2AX, p53 and p21 were activated in RIT-treated HCT116 cells and G2/M cell cycle arrest was observed. Moreover, the alkaline comet assay showed that DNA breaks accumulated when cells were placed at 4 °C during exposure but were repaired under standard RIT conditions (37 °C), suggesting that lesions detected under alkaline conditions (mostly DNA single strand breaks and alkali-labile sites) are efficiently repaired in treated cells. The level of gamma-H2AX protein corroborated by the level of foci measured in nuclei of treated cells was shown to accumulate with time thereby suggesting the continuous presence of DNA double strand breaks. This was accompanied by the formation of micronuclei. Conclusion: Hypersensitivity to non-internalizing 125I-mAbs is not due to lack of detection of DNA damage after low absorbed dose-rates. However, DNA double strand breaks accumulate in cells exposed both to internalizing and non-internalizing 125I-mAbs and lead to micronuclei formation. These results suggest impairment in DNA double strand breaks repair after low absorbed doses of 125I-mAbs

  12. Y-90-DOTA-hLL2: An Agent for Radioimmunotherapy of Non-Hodgkin's Lymphoma

    International Nuclear Information System (INIS)

    The goal of this work was to determine an optimal radioimmunotherapy agent for non-Hodgkin's lymphoma. We established the stability profile of yttrium-90-labeled humanized LL2 (hLL2) monoclonal antibody prepared with different chelating agents, and from these data estimated the improvement using the most stable yttrium-90 chelate-hLL2 complex. Methods: The complementary-determining region- (cdr)-grafted (humanized) anti-CD22 mAb, hLL2 (epratuzumab), was conjugated to derivatives of DTPA and 1,4,7,10-tetraazacyclododecane-N,N',N'',N'''-tetraacetic acid (DOTA). The conjugates were labeled with Y-90 and tested against a 10,000-fold molar excess of free DTPA and against human serum. The conjugates were also labeled with Y-88 and compared for biodistribution in normal and lymphoma xenograft-bearing athymic mice. In vivo data were analyzed for uptake of yttrium in bone and washed bone when either the DOTA or the Mx-DTPA chelates were used, and dosimetry calculations were made for each. Results: Y-90-DOTA -mAb were stable to either DTPA or serum challenge. DTPA complexes of hLL2 lost 3-4% of Y-90 (days 1-4) and 10-15% thereafter. In vivo, stability differences showed lower Y-90 uptake in bone using DOTA. Absorbed doses per 37 MBq (1 mCi) Y-90-mAb were 3555 and 5405 cGy for bone, and 2664 and 4524 cGy for washed-bone for 90Y-DOTA-hLL2 and 90Y-MxDTPA-hLL2, respectively, amounting to 52% and 69.8% increases in absorbed radiation doses for bone and washed-bone when switching from a DOTA to a Mx-DTPA chelate. Conclusion: Y-90-hLL2 prepared with the DOTA chelate represents a preferred agent for RAIT of non-Hodgkin's lymphoma, with an in vivo model demonstrating a large reduction in bone-deposited yttrium, as compared to yttrium-90-hLL2 agents prepared with open-chain DTPA-type chelating agents. Dosimetry suggests that this will result in a substantial toxicological advantage for a DOTA-based hLL2 conjugate

  13. Lutetium-177-G250 radioimmunotherapy in an intraperitoneal clear cell renal cell carcinoma xenograft model

    International Nuclear Information System (INIS)

    Full text of publication follows. Aim: Despite the good results achieved with agents targeting the VEGF and mTOR pathways, the treatment of advanced clear cell renal cell carcinoma (ccRCC) still poses a great challenge. A new approach in the treatment of ccRCC is radioimmunotherapy (RIT) using anti-carbonic anhydrase IX (CAIX) antibody G250. To investigate the potential of RIT with Lutetium-177 (Lu177) labeled G250, we conducted protein dose escalation study and subsequently a RIT study with Lu177-G250 in an intraperitoneal ccRCC mouse model. Materials and methods: 25 athymic female BALB/c mice were injected intraperitoneally with 3 x 106 SK-RC-52 cells. To determine the optimal G250 protein dose, 3 weeks after inoculation the mice were injected with either 1, 3, 10, 30 or 100 μg G250 radiolabeled with 15 MBq indium-111 (In111). SPECT/CT images were made with the micro SPECT USPECT II camera 48 hours p.i. After imaging, the mice are killed and the biodistribution of In111-G250 was determined. The optimal protein dose was used in a subsequent therapy experiment in 3 groups of mice with i.p. SK-RC-52 tumors. One group (n=10) was injected with 13 MBq Lu177-G250, a control group received nonspecific antibody MOPC21 labeled with 13 MBq Lu177 (n=10) and the second control group received 20 MBq In111-G250 (n=10). Tumor growth was monitored with SPECT/CT imaging before treatment and with 3 week intervals. Primary endpoints were overall survival and toxicity. Results: The optimal G250 protein dose to target ccRCC in this model was 10 μg G250, as determined with SPECT/CT imaging and biodistribution. Treatment with 13 MBq Lu177-G250 was well tolerated. Treatment with Lu177-G250 resulted in significantly prolonged median survival of 139 days, in comparison with 49 days (Lu177-MOPC21) and 53 days In111-G250 (p=0.015). Conclusion: this is the first RIT study with radiolabeled G250 protein in mice with i.p. growing ccRCC. Treatment with Lu177-G250 resulted in significantly

  14. Attempts to develop radioactive drugs in the treatment of cancer

    International Nuclear Information System (INIS)

    As an approach to improving the treatment of patients with some types of cancer, it appears to be important to attempt to develop radioactive drugs. These are compounds which, because of their chemical structure, are concentrated selectively in the viable malignant cells of tumors and carry incorporated radioactive atoms, which are responsible for the action of the drug, in sufficiently high specific activity, to the right places, in order to produce the radiotherapeutic effect in situ, and without significant damage to normal tissues. This method has been termed ''radiochemotherapy'' and can be regarded as including ''immunoradiotherapy'' using antitumor antibodies carrying radioactive atoms and tissue-specific therapy. Other macromolecular substances, e.g., natural and synthetic RNAs, may well prove to be of interest. However, most of the compounds studied so far have a relatively low molecular weight. The radioisotope must be bound firmly in the molecule both chemically and in vivo from the point of view of metabolic changes. Only agents used in systemic therapy will be considered here; endolymphatic therapy and the uses of radioactive colloids and of radioactive microspheres will be excluded. In general, the radioactive drugs are administered by intravenous injection, though in a number of cases intraarterial therapy has also been used

  15. Long non-coding RNAs in cancer drug resistance development.

    Science.gov (United States)

    Majidinia, Maryam; Yousefi, Bahman

    2016-09-01

    The presence or emergence of chemoresistance in tumor cells is a major burden in cancer therapy. While drug resistance is a multifactorial phenomenon arising from altered membrane transport of drugs, altered drug metabolism, altered DNA repair, reduced apoptosis rate and alterations of drug metabolism, it can also be linked to genetic and epigenetic factors. Long non-coding RNAs (lncRNAs) have important regulatory roles in many aspects of genome function including gene transcription, splicing, and epigenetics as well as biological processes involved in cell cycle, cell differentiation, development, and pluripotency. As such, it may not be surprising that some lncRNAs have been recently linked to carcinogenesis and drug resistance/sensitivity. Research is accelerating to decipher the exact molecular mechanism of lncRNA-regulated drug resistance and its therapeutic implications. In this article, we will review the structure, biogenesis, and mode of action of lncRNAs. Then, the involvement of lncRNAs in drug resistance will be discussed in detail. PMID:27427176

  16. Coping with a diagnosis of breast cancer-literature review and implications for developing countries.

    Science.gov (United States)

    Al-Azri, Mohammed; Al-Awisi, Huda; Al-Moundhri, Mansour

    2009-01-01

    Breast cancer is the most common cancer affecting women worldwide. Women are at an increased risk of developing both physical and psychological morbidity after diagnosis; however, many use different strategies to cope with the disease. The aim of this article is to review the available literature on the impact of breast cancer diagnoses and the strategies used by women to cope with this disease. The implications of these emerging findings are extrapolated within the context of health services provided in developing countries. Electronic databases were used to search the relevant literature. The findings showed that women who were diagnosed with breast cancer are at risk of developing several psychological morbidities such as depression, anxiety, fatigue, negative thoughts, suicidal thoughts, fear of dying, sense of aloneness, sexual and body images problems, as well as an overall decrease in the quality of life. Several strategies are used by women with breast cancer to cope with the disease, including positive cognitive restructuring, wishful thinking, emotional expression, disease acceptance, increased religious practice, family and social support, and yoga and exercise. Breast cancer diagnoses have been associated with several devastating psychological consequences; however, many women have used different coping strategies to adjust their lives accordingly. Healthcare professionals in developing countries, who work with women with breast cancer, should be aware of the different coping mechanisms that women use when diagnosed with cancer. Integrating a coping strategy into the treatment regimen would constitute an important milestone in the palliative care of patients with breast cancer. PMID:19686231

  17. Comparative efficacy of 177Lu and 90Y for Anti-CD20 Pretargeted Radioimmunotherapy in Murine Lymphoma Xenograft Models

    International Nuclear Information System (INIS)

    Purpose Pretargeted radioimmunotherapy (PRIT) is a multi-step method of selectively delivering high doses of radiotherapy to tumor cells while minimizing exposure to surrounding tissues. Yttrium-90 (90Y) and lutetium-177 (177Lu) are two of the most promising beta-particle emitting radionuclides used for radioimmunotherapy, which despite having similar chemistries differ distinctly in terms of radiophysical features. These differences may have important consequences for the absorbed dose to tumors and normal organs. Whereas 90Y has been successfully applied in a number of preclinical and clinical radioimmunotherapy settings, there have been few published pretargeting studies with 177Lu. We therefore compared the therapeutic potential of targeting either 90Y or 177Lu to human B-cell lymphoma xenografts in mice. Methods Parallel experiments evaluating the biodistribution, imaging, dosimetry, therapeutic efficacy, and toxicity were performed in female athymic nude mice bearing either Ramos (Burkitt lymphoma) or Granta (mantle cell lymphoma) xenografts, utilizing an anti-CD20 antibodystreptavidin conjugate (1F5-SA) and an 90Y- or 177Lu-labeled 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA)-biotin second step reagent. Results The two radionuclides displayed comparable biodistributions in tumors and normal organs; however, the absorbed radiation dose delivered to tumor was more than twice as high for 90Y (1.3 Gy/MBq) as for 177Lu (0.6 Gy/MBq). More importantly, therapy with 90Y-DOTAbiotin was dramatically more effective than with 177Lu-DOTA-biotin, with 100% of Ramos xenograft-bearing mice cured with 37 MBq 90Y, whereas 0% were cured using identical amounts of 177Lu-DOTA-biotin. Similar results were observed in mice bearing Granta xenografts, with 80% of the mice cured with 90Y-PRIT and 0% cured with 177Lu-PRIT. Toxicities were comparable with both isotopes. Conclusion 90Y was therapeutically superior to 177Lu for streptavidin-biotin PRIT approaches in

  18. Myeloablative radioimmunotherapies in the conditioning of patients with AML, MDS and multiple myeloma prior to stem cell transplantation

    International Nuclear Information System (INIS)

    Aggressive consolidation chemotherapy and hematopoietic stem cell transplantation have improved the prognosis of patients with acute myeloid leukemia (AML), myelodyplastic syndrome (MDS) and multiple myeloma. Nevertheless, only a minor fraction of patients achieve long-term disease-free survival after stem cell transplantation with disease recurrence being the most common cause of treatment failure. In addition, therapy-related effects such as toxicity of chemotherapy and complications of stem cell transplantation increase mortality rates significantly. Myeloablative radioimmunotherapy uses radiolabeled monoclonal antibodies (mAb) with affinity for the hematopoietic marrow. It applies high radiation doses in the bone marrow but spares normal organs. Adding myeloablative radioimmunotherapy to the conditioning schemes of AML, MDS and multiple myeloma before stem cell transplantation allows for the achievement of a pronounced antileukemic/antimyeloma effect for the reduction of relapse rates without significant increase of acute organ toxicity and therapy-related mortality. In order to optimise therapy, a rational design of the nuclide-antibody combination is necessary. 90Y, 188Re and 131I are the most frequently used β--particles. Of these, 90Y is the most qualified nuclide for myeloablation. Backbone stabilised DTPA are ideal chelators to stably conjugate 90Y to antibodies so far. For myeloablative conditioning, anti-CD66-, -45- and -33-mAb are used. The anti-CD66-antibody BW250/183 binds to normal hematopoietic cells but not to leukemic blasts and myeloma cells. The 90Y-2B3M-DTPA-BW250/183 is the most suited radioimmunoconjugate for patients with an infiltration grade of leukemic blasts in the bone marrow 90Y-anti-CD45-mAb YAML568 are 6.4 ± 1.2 (bone marrow), 3.9 ± 1.4 (liver) and 1.1 ± 0.4 (kidneys). CD45 is expressed also on the extramedullar clonogenic myeloma progenitor cell that circulates in the peripheral blood. Thus, the conditioning of patients with

  19. Comparative efficacy of 177Lu and 90Y for anti-CD20 pretargeted radioimmunotherapy in murine lymphoma xenograft models.

    Directory of Open Access Journals (Sweden)

    Sofia H L Frost

    Full Text Available Pretargeted radioimmunotherapy (PRIT is a multi-step method of selectively delivering high doses of radiotherapy to tumor cells while minimizing exposure to surrounding tissues. Yttrium-90 (90Y and lutetium-177 (177Lu are two of the most promising beta-particle emitting radionuclides used for radioimmunotherapy, which despite having similar chemistries differ distinctly in terms of radiophysical features. These differences may have important consequences for the absorbed dose to tumors and normal organs. Whereas 90Y has been successfully applied in a number of preclinical and clinical radioimmunotherapy settings, there have been few published pretargeting studies with 177Lu. We therefore compared the therapeutic potential of targeting either 90Y or 177Lu to human B-cell lymphoma xenografts in mice.Parallel experiments evaluating the biodistribution, imaging, dosimetry, therapeutic efficacy, and toxicity were performed in female athymic nude mice bearing either Ramos (Burkitt lymphoma or Granta (mantle cell lymphoma xenografts, utilizing an anti-CD20 antibody-streptavidin conjugate (1F5-SA and an 90Y- or 177Lu-labeled 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA-biotin second step reagent.The two radionuclides displayed comparable biodistributions in tumors and normal organs; however, the absorbed radiation dose delivered to tumor was more than twice as high for 90Y (1.3 Gy/MBq as for 177Lu (0.6 Gy/MBq. More importantly, therapy with 90Y-DOTA-biotin was dramatically more effective than with 177Lu-DOTA-biotin, with 100% of Ramos xenograft-bearing mice cured with 37 MBq 90Y, whereas 0% were cured using identical amounts of 177Lu-DOTA-biotin. Similar results were observed in mice bearing Granta xenografts, with 80% of the mice cured with 90Y-PRIT and 0% cured with 177Lu-PRIT. Toxicities were comparable with both isotopes.90Y was therapeutically superior to 177Lu for streptavidin-biotin PRIT approaches in these human lymphoma

  20. Development of Multifunctional Nanoparticles for Cancer Therapy Applications

    Science.gov (United States)

    Huth, Christopher

    The focus of this thesis is the functionalization and tailoring of nanoparticle surfaces to perform specific objectives in a biological environment. The nanoparticles examined include carbon nanotubes (CNTs), superparamagnetic iron oxide nanoparticles and superparamagnetic iron oxide nanocomposites. The unique nanomaterials have been developed to address continued issues in cancer therapy, including cancer diagnosis and efficient drug delivery. CNT surfaces were modified by plasma polymerization, providing functional groups for conjugation. Luminescent amine labeled quantum dots were fixed to the surface of the CNTs to aid in cancer diagnosis by in vivo imaging. Mice, injected with the quantum dot functionalized carbon nanotubes, were imaged displaying the in vivo imaging capability. In addition, the drug loading and drug release capabilities were examined by incorporating the drug paclitaxel into PLGA-coated CNTs, which showed much higher cytotoxicity to PC-3MM2 human prostate carcinoma cells compared to CNTs without paclitaxel. Paclitaxel was loaded at 112.5 microg/mg of PLGA-coated CNTs. Iron oxide nanocomposites were functionalized with quantum dots for diagnosis applications. Because the nanocomposites contain iron oxide, the nanoparticle provides the opportunity for magnetic hyperthermia, creating a unique material for diagnosis and therapy. Mice, injected with the quantum dot functionalized iron oxide nanocomposites, were imaged displaying the in vivo imaging capability. The magnetic hyperthermic property of the quantum dot functionalized nanocomposites was observed with the attainment of temperatures above 50°C during exposure to an alternating magnetic field. Thermoresponsive nanoparticles were prepared by immobilizing a 2 - 3 nm thick phospholipid layer on the surface of superparamagnetic Fe3O 4 nanoparticles via high affinity avidin/biotin interactions. Morphological and physicochemical surface properties were assessed using TEM, confocal laser scanning

  1. Biomarker-guided repurposing of chemotherapeutic drugs for cancer therapy: a novel strategy in drug development

    Directory of Open Access Journals (Sweden)

    Jan eStenvang

    2013-12-01

    Full Text Available Cancer is a leading cause of mortality worldwide and matters are only set to worsen as its incidence continues to rise. Traditional approaches to combat cancer include improved prevention, early diagnosis, optimized surgery, development of novel drugs and honing regimens of existing anti-cancer drugs. Although discovery and development of novel and effective anti-cancer drugs is a major research area, it is well known that oncology drug development is a lengthy process, extremely costly and with high attrition rates. Furthermore, those drugs that do make it through the drug development mill are often quite expensive, laden with severe side-effects and, unfortunately, to date, have only demonstrated minimal increases in overall survival. Therefore, a strong interest has emerged to identify approved non-cancer drugs that possess anti-cancer activity, thus shortcutting the development process. This research strategy is commonly known as drug repurposing or drug repositioning and provides a faster path to the clinics. We have developed and implemented a modification of the standard drug repurposing strategy that we review here; rather than investigating target-promiscuous non-cancer drugs for possible anti-cancer activity, we focus on the discovery of novel cancer indications for already approved chemotherapeutic anti-cancer drugs. Clinical implementation of this strategy is normally commenced at clinical phase II trials and includes pre-treated patients. As the response rates to any non-standard chemotherapeutic drug will be relatively low in such a patient cohort it is a pre-requisite that such testing is based on predictive biomarkers. This review describes our strategy of biomarker-guided repurposing of chemotherapeutic drugs for cancer therapy, taking the repurposing of topoisomerase I inhibitors and topoisomerase I as a potential predictive biomarker as case in point.

  2. In vitro and in vivo evaluation of direct rhenium-188-labeled anti-CD52 monoclonal antibody alemtuzumab for radioimmunotherapy of B-cell chronic lymphocytic leukemia

    Energy Technology Data Exchange (ETDEWEB)

    Decker, Mario de [Department of Radiopharmacy, Faculty of Pharmaceutical Sciences, Ghent University, Ghent (Belgium); Department of Nuclear Medicine and Molecular Imaging, University Medical Centre Groningen, Groningen (Netherlands)], E-mail: mario.dedecker@health.wa.gov.au; Bacher, Klaus; Thierens, Hubert [Department of Medical Physics and Radiation Protection, Ghent University, Ghent (Belgium); Slegers, Guido [Department of Medical Imaging of Domestic Animals, Ghent University, Ghent (Belgium); Dierckx, Rudi A. [Department of Nuclear Medicine and Molecular Imaging, University Medical Centre Groningen, Groningen (Netherlands); Vos, Filip de [Department of Radiopharmacy, Faculty of Pharmaceutical Sciences, Ghent University, Ghent (Belgium)

    2008-07-15

    Alemtuzumab (Campath, Berlex) is a humanized IgG1 rat monoclonal antibody directed against the cell surface CD52 antigen, found on lymphocytes and monocytes. It is being developed for the treatment of chronic lymphocytic leukemia (CLL), autoimmune disease and for the prevention of transplant rejection. This study focused on synthesis, quality control, in vitro evaluation and biodistrubution of {sup 188}Re-labeled alemtuzumab for radioimmunotherapy of B-cell CLL. {sup 188}Re-alemtuzumab was synthesized using a direct radiolabeling method. Reduction of the intramolecular disulfide bonds of the antibody was performed with tris-(carboxyethyl)-phosphine (Pierce), using a 1:60 molar excess. Reaction took place at room temperature for 20 min. A PD-10 desalting column was used to purify the reduced antibody from excess phospine. Complexation and transchelation of {sup 188}ReO{sub 4}{sup -} was achieved using sodium gluconate as weak chelator and SnCl{sub 2} as reducing agent. Quality control was done using instant thin-layer chromatography. Binding assays were performed on a CD52-positive cell line (HuT-78). Female NMRI mice were injected intravenously with 20 {mu}g radiolabeled alemtuzumab and killed at preset time intervals for biodistribution studies. Tissues were dissected, weighed and counted for determination of radioactivity. Data were expressed as percentage injected activity per gram of tissue (% IA/g tissue) or as percentage injected activity (% IA). {sup 188}Re-alemtuzumab was prepared achieving high radiochemical yields. Labeling efficiency of more than 95% can be obtained using optimal reaction conditions. {sup 188}Re-alemtuzumab showed good in vitro stability, remaining intact at 24 h after radiolabeling. In mice, {sup 188}Re-alemtuzumab showed high uptake in the blood (25.10{+-}1.36% IA at 1 h p.i.), followed by a biexponential clearance (t{sub 1/2{alpha}}=4.790 h and t{sub 1/2{beta}}=55.45 h). Increased uptake was observed in kidneys and heart (9

  3. Using intervention mapping to develop a work-related guidance tool for those affected by cancer

    OpenAIRE

    Munir Fehmidah; Kalawsky Katryna; Wallis Deborah J; Donaldson-Feilder Emma

    2013-01-01

    Abstract Background Working-aged individuals diagnosed and treated for cancer require support and assistance to make decisions regarding work. However, healthcare professionals do not consider the work-related needs of patients and employers do not understand the full impact cancer can have upon the employee and their work. We therefore developed a work-related guidance tool for those diagnosed with cancer that enables them to take the lead in stimulating discussion with a range of different ...

  4. Development and application of statistical methods for population-based cancer patient survival

    OpenAIRE

    Eloranta, Sandra

    2013-01-01

    The overarching aim of this work has been to develop and apply statistical methods for estimating cancer patient survival from population-based register data. Particular focus has been on statistical methods that can be used for presenting cancer survival statistics from administrative health data registers in a manner that is relevant for physicians and patients. Study 1: In this study we clarify and discuss the relative merits of estimates of crude and net cancer patient survival, resp...

  5. A Case of Ampullary Adenoma that Developed to Cancer 7 Years After Initial Diagnosis

    OpenAIRE

    Iwashita, Yuji; Ito, Kei; Noda, Yutaka; Koshita, Shinsuke; Kanno, Yoshihide; Ogawa, Takahisa; Masu, Kaori; Michikawa, Yosuke

    2015-01-01

    Patient: Male, 81 Final Diagnosis: Ampullary cancer Symptoms: Jaundice Medication: — Clinical Procedure: Endoscopy Specialty: Gastroenterology and Hepatology Objective: Unusual clinical course Background: Although ampullary adenomas have been reported to be considered as precancerous lesions, there have been very few reports of cases in which cancer occurred after long-term follow-up. We herein report a case of ampullary adenoma that developed to cancer after long-term observation. Case Repor...

  6. Prediagnostic serum levels of inflammatory biomarkers are correlated with future development of lung and esophageal cancer

    OpenAIRE

    Keeley, Brieze R; Islami, Farhad; Pourshams, Akram; Poustchi, Hossein; Pak, Jamie S; Brennan, Paul; Khademi, Hooman; Genden, Eric M.; Abnet, Christian C.; Dawsey, Sanford M.; Boffetta, Paolo; Malekzadeh, Reza; Sikora, Andrew G.

    2014-01-01

    This study tests the hypothesis that prediagnostic serum levels of 20 cancer-associated inflammatory biomarkers correlate directly with future development of head and neck, esophageal, and lung cancers in a high-risk prospective cohort. This is a nested case–control pilot study of subjects enrolled in the Golestan Cohort Study, an ongoing epidemiologic project assessing cancer trends in Golestan, Iran. We measured a panel of 20 21cytokines, chemokines, and inflammatory molecules using Luminex...

  7. Current opinion on the role of testosterone in the development of prostate cancer: a dynamic model

    OpenAIRE

    Xu, Xiaohui; Chen, Xinguang (Jim); Hu, Hui; Dailey, Amy B.; Taylor, Brandie D.

    2015-01-01

    Background Since the landmark study conducted by Huggins and Hodges in 1941, a failure to distinguish between the role of testosterone in prostate cancer development and progression has led to the prevailing opinion that high levels of testosterone increase the risk of prostate cancer. To date, this claim remains unproven. Presentation of the hypothesis We present a novel dynamic mode of the relationship between testosterone and prostate cancer by hypothesizing that the magnitude of age-relat...

  8. The pathobiological impact of cigarette smoke on pancreatic cancer development (Review)

    OpenAIRE

    Wittel, Uwe A; Momi, Navneet; SEIFERT, GABRIEL; Wiech, Thorsten; Hopt, Ulrich T.; Batra, Surinder K.

    2012-01-01

    Despite extensive efforts, pancreatic cancer remains incurable. Most risk factors, such as genetic disposition, metabolic diseases or chronic pancreatitis cannot be influenced. By contrast, cigarette smoking, an important risk factor for pancreatic cancer, can be controlled. Despite the epidemiological evidence of the detrimental effects of cigarette smoking with regard to pancreatic cancer development and its unique property of being influenceable, our understanding of cigarette smoke-induce...

  9. Roles of Foxp3 in the occurrence and development of cervical cancer

    OpenAIRE

    Luo, Qingshuang; Zhang, Shulan; Wei, Heng; Pang, Xiaoao; Zhang, Huijie

    2015-01-01

    Objective: This study aimed to evaluate the relationship between forkhead box P3 (Foxp3) expression and clinicopathological characteristics of cervical cancer and to explore the influence of Foxp3 on the biological behaviors of cervical cancer cells. Methods: In this study, immunohistochemistry, lentivirus mediated transfection, Transwell assay; CCK-8 assay, real-time PCR and flow cytometry were employed to confirm the roles of Foxp3 in the occurrence and development of cervical cancer. Resul...

  10. Development of an immunotherapeutic adenovirus targeting hormone-independent prostate cancer

    OpenAIRE

    Kim JS; Lee SD; Lee SJ; Chung MK

    2013-01-01

    Jae Sik Kim,1 Sang Don Lee,2 Sang Jin Lee,3 Moon Kee Chung21Department of Urology, The Catholic University of Korea Incheon St Mary's Hospital, Incheon, 2Pusan National University Yangsan Hospital and Research Institute for Convergence of Biomedical Science and Technology, Yangsan, 3Genitourinary Cancer Branch, National Cancer Center, Goyang, KoreaBackground: To develop a targeting therapy for hormone-independent prostate cancer, we constructed and characterized conditionally replicating ...

  11. Review of theories on development of ovarian cancer. Leptin as a potential agent engaged in carcinogenesis

    International Nuclear Information System (INIS)

    Many different hypotheses and theories have been formulated regarding the development of sporadic ovarian cancer. The augmented risk is associated with nulliparity or low fecundity. Apart from changes in the genital system, leptin can be linked in several ways to infertility or low fecundity, from poor alimentation (severe dieting) and its effects on the hypothalamushypophysis-ovary axis to improper blastocyst implantation in the endometrium. Ovulation used to be regarded as representing one of the factors which promote the development of ovarian cancer due to the associated lesions of the ovarian epithelium and the development of inclusion cysts. The risk is reduced by the long-term use of contraceptive pills. However, it has been demonstrated, that hormonal contraception is linked to the stabilization of plasma leptin levels and that it, possibly, has less pronounced effects on target tissues. In view of the suggestions on leptin involvement, the hypothesis regarding the effects of HRT on ovarian cancer development remains unsupported since leptin levels during a course of HRT manifest no increases or decreases- they remain stable. The inflammatory theory of ovarian cancer development might also be linked to the potential involvement of leptin in the pathogenesis of endometriosis, promoting endometrioid and clarocellular ovarian cancers. Leptin has been shown to be linked to the development of endometriosis, particularly due to its mitogenic and angiogenic effects. Bilateral ovariectomy, aimed at preventing the development of ovarian cancer, induces a decrease in serum leptin levels, in contrast to the reversible effects of pharmacological gonadectomy. Ovarian cancer develops more frequently in women who have high living standards, which is significantly associated with increased BMI and augmented serum leptin levels. The described theory concerning the two pathways of ovarian cancer development, including one typical for more aggressive serous cancers, may

  12. Host microenvironment in breast cancer development: Inflammatory cells, cytokines and chemokines in breast cancer progression: reciprocal tumor–microenvironment interactions

    International Nuclear Information System (INIS)

    A comprehensive overview of breast cancer development and progression suggests that the process is influenced by intrinsic properties of the tumor cells, as well as by microenvironmental factors. Indeed, in breast carcinoma, an intensive interplay exists between the tumor cells on one hand, and inflammatory cells/cytokines/chemokines on the other. The purpose of the present review is to outline the reciprocal interactions that exist between these different elements, and to shed light on their potential involvement in breast cancer development and progression

  13. Monte Carlo Calculation of Radioimmunotherapy with 90Y-, 177Lu-, 131I-, 124I-, and 188Re-Nanoobjects: Choice of the Best Radionuclide for Solid Tumour Treatment by Using TCP and NTCP Concepts

    Directory of Open Access Journals (Sweden)

    S. Lucas

    2015-01-01

    Full Text Available Radioimmunotherapy has shown that the use of monoclonal antibodies combined with a radioisotope like 131I or 90Y still remains ineffective for solid and radioresistant tumour treatment. Previous simulations have revealed that an increase in the number of 90Y labelled to each antibody or nanoobject could be a solution to improve treatment output. It now seems important to assess the treatment output and toxicity when radionuclides such as 90Y, 177Lu, 131I, 124I, and 188Re are used. Tumour control probability (TCP and normal tissue complication probability (NTCP curves versus the number of radionuclides per nanoobject were computed with MCNPX to evaluate treatment efficacy for solid tumours and to predict the incidence of surrounding side effects. Analyses were carried out for two solid tumour sizes of 0.5 and 1.0 cm radius and for nanoobject (i.e., a radiolabelled antibody distributed uniformly or nonuniformly throughout a solid tumour (e.g., Non-small-cell-lung cancer (NSCLC. 90Y and 188Re are the best candidates for solid tumour treatment when only one radionuclide is coupled to one carrier. Furthermore, regardless of the radionuclide properties, high values of TCP can be reached without toxicity if the number of radionuclides per nanoobject increases.

  14. Clinical development of cancer therapeutics that target metabolism.

    Science.gov (United States)

    Clem, B F; O'Neal, J; Klarer, A C; Telang, S; Chesney, J

    2016-06-01

    Glucose and glutamine metabolism in cancer cells are markedly elevated relative to non-transformed normal cells. This metabolic reprogramming enables the production of adenosine triphosphate and the anabolic precursors needed for survival, growth and motility. The recent observations that mutant oncogenic proteins and the loss of tumor suppressors activate key metabolic enzymes suggest that selective inhibition of these enzymes may yield effective cancer therapeutics with acceptable toxicities. In support of this concept, pre-clinical studies of small molecule antagonists of several metabolic enzymes in tumor-bearing mice have demonstrated reasonable therapeutic indices. We will review the rationale for targeting metabolic enzymes as a strategy to treat cancer and will detail the results of several recent clinical trials of metabolic inhibitors in advanced cancer patients. PMID:26428335

  15. Radioimmunotherapy using {sup 131}I-rituximab in patients with advanced stage B-cell non-Hodgkin's lymphoma: initial experience

    Energy Technology Data Exchange (ETDEWEB)

    Bienert, Maren; Reisinger, Ingrid; Humplik, Beatrice I.; Reim, Christel; Kroessin, Thomas; Avril, Norbert; Munz, Dieter L. [Charite - Universitaetsmedizin Berlin, Clinic for Nuclear Medicine, Berlin (Germany); Srock, Stefanie; Pezzutto, Antonio [Charite - Universitaetsmedizin Berlin, Department of Haematology and Oncology, Berlin (Germany)

    2005-10-01

    The aim of this study was to evaluate the safety, toxicity and therapeutic response of non-myeloablative radioimmunotherapy using {sup 131}I-rituximab in previously heavily treated patients with B-cell non-Hodgkin's lymphoma (B-NHL). Nine patients with relapsed, refractory or transformed B-NHL received ten radioimmunotherapies. Patients had a median of 5 (range 2-7) prior standard therapies. Four patients had received prior high-dose chemotherapy followed by autologous stem cell transplantation, and eight had received prior rituximab therapy. Histopathology consisted of four mantle cell, one follicular and four diffuse large B-cell lymphomas. Rituximab, a monoclonal chimeric anti-CD20 antibody (IDEC-C2B8), was labelled with {sup 131}I using the Iodogen method. The administered activity (2,200{+-}600 MBq) was based on a dosimetrically calculated 45 cGy total-body radiation dose. All patients received an infusion of 2.5 mg/kg of rituximab prior to administration of the radiopharmaceutical. No acute adverse effects were observed after the administration of{sup 131}I-rituximab. Radioimmunotherapy was safe in our patient group and achieved one complete response ongoing at 14 months and two partial responses progressing at 12 and 13 months after treatment. One partial responder was re-treated with radioimmunotherapy and achieved an additional progression-free interval of 7 months. Four non-responders with bulky disease died 4.8{+-}2.0 months after therapy. Three patients had an elevated serum lactate dehydrogenase (LDH) level prior to radioimmunotherapy and none of the patients responded. Of two patients who received radioimmunotherapy as an additional treatment after salvage chemotherapy, one continues to be disease-free at 9 months and one relapsed at 5 months' follow-up. Reversible grade 3 or 4 haematological toxicity occurred in seven of nine patients. Median nadirs were 35 days for platelets, 44 days for leucocytes and 57 days for erythrocytes. (orig.)

  16. Development of cabozantinib for the treatment of prostate cancer

    Directory of Open Access Journals (Sweden)

    Vaishampayan UN

    2014-04-01

    Full Text Available Ulka N VaishampayanDepartment of Oncology, Wayne State University/Karmanos Cancer Institute, Detroit, MI, USAAbstract: Cabozantinib (XL184 is a multitargeted receptor tyrosine kinase with predominantly MET and vascular endothelial growth factor inhibition properties. It is currently approved by the US Food and Drug Administration for the treatment of progressive metastatic medullary thyroid cancer. The agent has a convenient once-daily oral dosing schedule and has demonstrated encouraging activity in metastatic castrate-resistant prostate cancer (CRPC. A Phase I/II trial demonstrated responses in soft tissue, visceral disease, and bone metastases in CRPC. An objective response rate of 5%, a stable disease rate of 75%, and a median progression-free survival of 6 months was observed. As compared with the 140 mg daily dose used in thyroid cancer, a lower dose of 60 mg daily is currently being utilized in prostate cancer studies due to the fact that toxicity could be reduced without compromising efficacy. Randomized trials are ongoing in comparison with prednisone or with mitoxantrone and prednisone in pretreated metastatic CRPC. Cabozantinib has demonstrated a unique mechanism of action and preliminary efficacy in the crowded therapeutic field of prostate cancer. Since multiple therapies have recently demonstrated overall survival benefit in metastatic CRPC, cabozantinib will likely face some challenges in clinical application. At present, in this rapidly evolving field, it is unclear what proportion of patients with prostate cancer will be eligible to receive this therapy. The cost of cabozantinib is likely to be another deterrent, especially if it remains more expensive than other oral therapies, such as abiraterone and enzalutamide. Defining the role of MET overexpression and RET mutations as biomarkers in prostate cancer may help to guide patient selection, and enrich and enhance the future applications of this targeted novel agent.Keywords: XL

  17. Developing EZH2-Targeted Therapy for Lung Cancer.

    Science.gov (United States)

    Frankel, Arthur E; Liu, Xin; Minna, John D

    2016-09-01

    Epigenetic targets are exciting new avenues for cancer drug discovery. Zhang and colleagues have designed the open-source EZH2 inhibitor JQEZ5 and shown antitumor efficacy in vitro and in vivo in preclinical studies in murine and human lung adenocarcinoma models expressing high levels of EZH2. Cancer Discov; 6(9); 949-52. ©2016 AACRSee related article by Zhang and colleagues, p. 1006. PMID:27587466

  18. Development of hematin conjugated PLGA nanoparticle for selective cancer targeting.

    Science.gov (United States)

    Amin, Md Lutful; Kim, Dami; Kim, SeJin

    2016-08-25

    Targeted nanomedicine for cancer therapy has gained widespread popularity and is being extensively explored. Porphyrins have intrinsic tumor localizing ability and have been studied for photodynamic therapy. However, they have not been used as cancer targeting agents for nanomedicines. In this study, PLGA nanoparticles were formulated and an iron-containing blood porphyrin, hematin was conjugated to the surface of the nanoparticles to investigate selectivity towards cancer cell and cellular internalization. Hematin was previously shown to facilitate growth and proliferation of cancer cells. PLGA nanoparticles were characterized by FE-SEM, AFM, DLS, and Zeta potential analyzer. The conjugation of hematin was confirmed by FTIR. HeLa cells were used to study tumor selectivity and uptake. Hematin conjugated particles (ζ potential: -15.19mV) showed higher affinity towards the cancer cells than the control particles. The result indicated that the particles were internalized by heme carrier protein-1. Together these data suggest that hematin is a promising cancer targeting material for nanotherapeutics. PMID:27260086

  19. Bivalent fragment of the ior-CEA1 antibody. A challenge to the positive CEA tumors radioimmunotherapy

    International Nuclear Information System (INIS)

    The directed radiotherapy of the solid tumors with fragments recombinants of radiolabelled antibodies is a topic of current investigation, so much at preclinical level as clinical. This work describes the preclinical characterization of a new fragment type diabody of the AcMo ior CEA1 that has been labelled with 131 I for their use in the diagnosis and the therapy of CEA positive tumors. The radiolabelling methodology used allows the incorporation of more than 90% of the radio iodine to the molecule without committing the capacity of recognition of its antigen significantly. The combination of the favourable properties pharmacy kinetic and high selective accumulation in the tumor, they make of the diabody anti CEA an appropriate candidate for the radioimmunodiagnosis and the radioimmunotherapy of tumors that expresses CEA (Author)

  20. 78 FR 11895 - Prospective Grant of Exclusive License: Development of MUC-1 Tumor Associated Antigens as Cancer...

    Science.gov (United States)

    2013-02-20

    ...-1 Tumor Associated Antigens as Cancer Vaccines for Bladder Cancer, Breast Cancer, Colorectal Cancer, Gastric Cancer, Kidney Cancer, Liver Cancer, Lung Cancer, Ovarian Cancer, Prostate Cancer and Pancreatic..., gastric cancer, kidney cancer, liver cancer, lung cancer, ovarian......

  1. REAL PICTURE OF CANCER IN BANGLADESH, A DEVELOPING SOUTH ASIAN COUNTRY: A SURVEY STUDY

    OpenAIRE

    Hasib Sheikh*, A.M. Rashedul Hasan , M.H. Rahman , S. M. Hossain and Mithilesh Kumar Jha

    2012-01-01

    Cancer - one of the most pervasive diseases, thus far mostly in affluent countries - is fast raising its ugly head in the developing world. This is a survey work on cancer due to recent increasing of the number of cancer patients in Bangladesh. This study was carried out in Ahsania Mission Cancer Hospital, Dhaka Bangladesh as this is the biggest missionary hospital in this country, From 13 February 2011 to April 13, 2011. A total of 352 patients were enrolled in the study. Of them 160 were m...

  2. Single-dose anti-CD138 radioimmunotherapy: bismuth-213 is more efficient than lutetium-177 for treatment of multiple myeloma in a preclinical model

    Directory of Open Access Journals (Sweden)

    Nolwenn eFichou

    2015-11-01

    Full Text Available Objectives: Radioimmunotherapy (RIT has emerged as a potential treatment option for multiple myeloma (MM. In humans, a dosimetry study recently showed the relevance of RIT using an antibody targeting the CD138 antigen. The therapeutic efficacy of RIT using an anti-CD138 antibody coupled to 213Bi, an α-emitter, was also demonstrated in a preclinical MM model. Since then, RIT with β-emitters has shown efficacy in treating hematologic cancer. In this paper, we investigate the therapeutic efficacy of RIT in the 5T33 murine MM model using a new anti-CD138 monoclonal antibody labeled either with 213Bi for α-RIT or 177Lu for β-RIT.Methods: A new monoclonal anti-CD138 antibody, 9E7.4, was generated by immunizing a rat with a murine CD138-derived peptide. Antibody specificity was validated by flow cytometry, biodistribution and α-RIT studies. Then, a β-RIT dose-escalation assay with the 177Lu-radiolabeled 9E7.4 mAb was performed in KalwRij C57/BL6 mice 10 days after i.v. engraftment with 5T33 MM cells. Animal survival and toxicological parameters were assessed to define the optimal activity.Results: α-RIT performed with 3.7 MBq of 213Bi-labeled 9E7.4 anti-CD138 mAb increased median survival to 80 days compared to 37 days for the untreated control and effected cure in 45% of animals. β-RIT performed with 18.5 MBq of 177Lu-labeled 9E7.4 mAb was well tolerated and significantly increased mouse survival (54 versus 37 days in the control group; however, no mice were cured with this treatment.Conclusion: This study revealed the advantages of α-RIT in the treatment of MM in a preclinical model where β-RIT shows almost no efficacy.

  3. Development and Evaluation of a Theory-Based Physical Activity Guidebook for Breast Cancer Survivors

    Science.gov (United States)

    Vallance, Jeffrey K.; Courneya, Kerry S.; Taylor, Lorian M.; Plotnikoff, Ronald C.; Mackey, John R.

    2008-01-01

    This study's objective was to develop and evaluate the suitability and appropriateness of a theory-based physical activity (PA) guidebook for breast cancer survivors. Guidebook content was constructed based on the theory of planned behavior (TPB) using salient exercise beliefs identified by breast cancer survivors in previous research. Expert…

  4. Development of a next generation Semliki Forest virus-based DNA vaccine against cervical cancer

    NARCIS (Netherlands)

    Van De Wall, Stephanie; Ljungberg, Karl; Peng IP, Peng; Boerma, Annemarie; Nijman, Hans W.; Liljeström, Peter; Daemen, Toos

    2014-01-01

    Cervical cancer is the second most prevalent cancer among women worldwide. The disease develops as a result of infection with high-risk human papillomavirus (HPV) through persistent expression of early proteins E6 and E7 with transforming capacities in cervical epithelial cells. Our group pioneered

  5. Initial evaluation of 227Th-p-benzyl-DOTA-rituximab for low-dose rate α-particle radioimmunotherapy

    International Nuclear Information System (INIS)

    Radioimmunotherapy has proven clinically effective in patients with non-Hodgkin's lymphoma. Radioimmunotherapy trials have so far been performed with β-emitting isotopes. In contrast to β-emitters, the shorter range and high linear energy transfer (LET) of α particles allow for more efficient and selective killing of individually targeted tumor cells. However, there are several obstacles to the use of α-particle immunotherapy, including problems with chelation chemistry and nontarget tissue toxicity. The α-emitting radioimmunoconjugate 227Th-DOTA-p-benzyl-rituximab is a new potential anti-lymphoma agent that might overcome some of these difficulties. The present study explores the immunoreactivity, in vivo stability and biodistribution, as well as the effect on in vitro cell growth, of this novel radioimmunoconjugate. To evaluate in vivo stability, uptake in balb/c mice of the α-particle-emitting nuclide 227Th alone, the chelated form, 227Th-p-nitrobenzyl-DOTA and the radioimmunoconjugate 227Th-DOTA-p-benzyl-rituximab was compared in a range of organs at increasing time points after injection. The immunoreactive fraction of 227Th-DOTA-p-benzyl-rituximab was 56-65%. During the 28 days after injection of radioimmunoconjugate only, very modest amounts of the 227Th had detached from DOTA-p-benzyl-rituximab, indicating a relevant stability in vivo. The half-life of 227Th-DOTA-p-benzyl-rituximab in blood was 7.4 days. Incubation of lymphoma cells with 227Th-DOTA-p-benzyl-rituximab resulted in a significant antigen-dependent inhibition of cell growth. The data presented here warrant further studies of 227Th-DOTA-p-benzyl-rituximab

  6. Effects of ongoing smoking on the development of radiation-induced pneumonitis in breast cancer and oesophagus cancer patients

    International Nuclear Information System (INIS)

    Purpose: To investigate the influence of smoking on the development of radiation-induced pneumonitis in patients treated for breast and oesophagus cancer. Materials and methods: This is a retrospective study on 405 females diagnosed with primary unilateral breast cancer stages 1 and 2 and 201 oesophagus carcinoma patients. The possibilities in Sweden to obtain detailed information from different medical records were used to collect data on smoking habits, radiation treatment and spontaneously reported pneumonitis. Radiation-induced pneumonitis was defined as a combination of roentgenographic infiltrate in the lung field involving an irradiated area on the chest X-ray and clinical symptoms such as non-productive cough and dyspnoea. Results: Six breast cancer patients had spontaneously reported pneumonitis. Five of them were non-smokers (P=0.182) and the other was a former smoker. Eight of the oesophagus cancer patients had spontaneously reported radiation-induced clinical pneumonitis and they were all non-smokers (P=0.022), except one, who was a pipe smoker. None of the patients who were cigarette smokers were recorded as developing clinical pneumonitis after irradiation. Conclusion: These data could support the previous clinical observations and experimental studies that smoking depresses the frequency of radiation-induced pneumonitis. The present study as well as earlier observations could justify further studies concerning the possibility of an interaction of smoking with cancer treatment, both from the view of therapeutic failures and reduced adverse effects. (Copyright (c) 1998 Elsevier Science B.V., Amsterdam. All rights reserved.)

  7. Targeting tumorigenesis: development and use of mTOR inhibitors in cancer therapy

    Directory of Open Access Journals (Sweden)

    Kay Andrea

    2009-10-01

    Full Text Available Abstract The mammalian target of rapamycin (mTOR is an intracellular serine/threonine protein kinase positioned at a central point in a variety of cellular signaling cascades. The established involvement of mTOR activity in the cellular processes that contribute to the development and progression of cancer has identified mTOR as a major link in tumorigenesis. Consequently, inhibitors of mTOR, including temsirolimus, everolimus, and ridaforolimus (formerly deforolimus have been developed and assessed for their safety and efficacy in patients with cancer. Temsirolimus is an intravenously administered agent approved by the US Food and Drug Administration (FDA and the European Medicines Agency (EMEA for the treatment of advanced renal cell carcinoma (RCC. Everolimus is an oral agent that has recently obtained US FDA and EMEA approval for the treatment of advanced RCC after failure of treatment with sunitinib or sorafenib. Ridaforolimus is not yet approved for any indication. The use of mTOR inhibitors, either alone or in combination with other anticancer agents, has the potential to provide anticancer activity in numerous tumor types. Cancer types in which these agents are under evaluation include neuroendocrine tumors, breast cancer, leukemia, lymphoma, hepatocellular carcinoma, gastric cancer, pancreatic cancer, sarcoma, endometrial cancer, and non-small-cell lung cancer. The results of ongoing clinical trials with mTOR inhibitors, as single agents and in combination regimens, will better define their activity in cancer.

  8. Ixabepilone development across the breast cancer continuum: a paradigm shift

    Directory of Open Access Journals (Sweden)

    Nuhad K Ibrahim

    2010-06-01

    Full Text Available Nuhad K IbrahimDepartment of Breast Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USAAbstract: The epothilone analog ixabepilone exhibits reduced susceptibility to several important tumor survival mechanisms that limit the efficacy of taxanes and anthracyclines. As a single agent, ixabepilone has shown promise in metastatic breast cancer when anthracyclines, taxanes, or capecitabine have failed; and in early-stage breast cancer that is taxane-naïve or has previously received taxanes in the adjuvant or metastatic setting. Compared with capecitabine alone, ixabepilone used in combination with capecitabine in patients previously treated with and resistant to anthracyclines and taxanes produced a 25% reduction in the risk of disease progression. Triple-negative tumors showed particular susceptibility to this doublet. Ixabepilone has also demonstrated efficacy as first-line therapy in combination with targeted agents such as bevacizumab and trastuzumab. Ongoing investigations should provide insight as to how this agent could be integrated into treatment of early-stage disease. In clinical studies, toxicities with ixabepilone were manageable and reversible through dose reduction or delay, even in patients with extensive or heavily-pretreated disease. Thus, ixabepilone represents a useful addition to the therapeutic options available for advanced breast cancer, and it may extend progression-free survival in patients with limited treatment options.Keywords: ixabepilone, breast cancer, efficacy, metastasis, adjuvant

  9. The role of DNA methylation in cancer development.

    Directory of Open Access Journals (Sweden)

    Michał W Luczak

    2006-09-01

    Full Text Available Epigenetic modifications include DNA methylation and covalent modification of histones. These alterations are reversible but very stable and exert a significant impact on the regulation of gene expression. Changes in methylation of promoter or first exon may mimic the effect of mutations of various tumor suppressor genes (TSGs or protooncogenes. Carcinogenesis can also result from aberrations in genomic DNA methylation that include hypermethylation and hypomethylation of promoter or first exon of cancer-related genes. Hypermethylation of promoter of various TSGs causes their transcriptional silencing. However, hypomethylation of regulatory DNA sequences activates transcription of protooncogenes, retrotransposons, as well as genes encoding proteins involved in genomic instability and malignant cell metastasis. The methylation of genomic DNA in malignant cells is catalyzed by DNA methyltransferases DNMT1 and DNMT3B, revealing significantly elevated expression in different types of cancers. The reversibility of hypermethylation can be used as target of therapeutic treatment in cancer. DNMT 1 and DNMT3B inhibitors including 5-Aza-2'-deoxycytidine and antisense oligonucleotides have been applied in clinical trials of such treatment. Identification of aberrations of DNA methylation in cancer cells is a new field of investigation in carcinogenesis. We believe that epigenetic cancer diagnostic and therapy will be achieved in the next decades.

  10. Prediagnostic serum levels of inflammatory biomarkers are correlated with future development of lung and esophageal cancer.

    Science.gov (United States)

    Keeley, Brieze R; Islami, Farhad; Pourshams, Akram; Poustchi, Hossein; Pak, Jamie S; Brennan, Paul; Khademi, Hooman; Genden, Eric M; Abnet, Christian C; Dawsey, Sanford M; Boffetta, Paolo; Malekzadeh, Reza; Sikora, Andrew G

    2014-09-01

    This study tests the hypothesis that prediagnostic serum levels of 20 cancer-associated inflammatory biomarkers correlate directly with future development of head and neck, esophageal, and lung cancers in a high-risk prospective cohort. This is a nested case-control pilot study of subjects enrolled in the Golestan Cohort Study, an ongoing epidemiologic project assessing cancer trends in Golestan, Iran. We measured a panel of 20 21 cytokines, chemokines, and inflammatory molecules using Luminex technology in serum samples collected 2 or more years before cancer diagnosis in 78 aerodigestive cancer cases and 81 controls. Data was analyzed using Wilcoxon rank sum test, odds ratios, receiver operating characteristic areas of discrimination, and multivariate analysis. Biomarkers were profoundly and globally elevated in future esophageal and lung cancer patients compared to controls. Odds ratios were significant for association between several biomarkers and future development of esophageal cancer, including interleukin-1Rα (IL-1Ra; 35.9), interferon α2 (IFN-a2; 34.0), fibroblast growth factor-2 (FGF-2; 17.4), and granulocyte/macrophage colony-stimulating factor (GM-CSF; 17.4). The same pattern was observed among future lung cancer cases for G-CSF (27.7), GM-CSF (13.3), and tumor necrosis factor-α (TNF-a; 8.6). By contrast, the majority of biomarkers studied showed no significant correlation with future head and neck cancer development. This study provides the first direct evidence that multiple inflammatory biomarkers are coordinately elevated in future lung and esophageal cancer patients 2 or more years before cancer diagnosis. PMID:25040886

  11. CANCER

    Directory of Open Access Journals (Sweden)

    N. Kavoussi

    1973-09-01

    Full Text Available There are many carcinogenetic elements in industry and it is for this reason that study and research concerning the effect of these materials is carried out on a national and international level. The establishment and growth of cancer are affected by different factors in two main areas:-1 The nature of the human or animal including sex, age, point and method of entry, fat metabolism, place of agglomeration of carcinogenetic material, amount of material absorbed by the body and the immunity of the body.2 The different nature of the carcinogenetic material e.g. physical, chemical quality, degree of solvency in fat and purity of impurity of the element. As the development of cancer is dependent upon so many factors, it is extremely difficult to determine whether a causative element is principle or contributory. Some materials are not carcinogenetic when they are pure but become so when they combine with other elements. All of this creates an industrial health problem in that it is almost impossible to plan an adequate prevention and safety program. The body through its system of immunity protects itself against small amounts of carcinogens but when this amount increases and reaches a certain level the body is not longer able to defend itself. ILO advises an effective protection campaign against cancer based on the Well –equipped laboratories, Well-educated personnel, the establishment of industrial hygiene within factories, the regular control of safety systems, and the implementation of industrial health principles and research programs.

  12. Recommendations for cervical cancer screening programs in developing countries: the need for equity and technological development

    Directory of Open Access Journals (Sweden)

    Lazcano-Ponce Eduardo

    2003-01-01

    Full Text Available The cervical cancer screening programs (CCSP have not been very efficient in the developing countries. This explains the need to foster changes on policies, standards, quality control mechanisms, evaluation and integration of new screening alternatives considered as low and high cost, as well as to regulate colposcopy practices and the foundation of HPV laboratories. Cervical cancer (CC is a disease most frequently found in poverty-stricken communities and reflecting a problem of equity at both levels gender and regional, and this, is not only due to social and economic development inequalities, but to the infrastructure and human resources necessary for primary care. For this reason, the CCSP program must be restructured, a to primarily address unprivileged rural and urban areas; b to foster actions aimed at ensuring extensive coverage as well as a similar quality of that coverage in every region; c to use screening strategies in keeping with the availability of health care services. In countries with a great regional heterogeneity, a variety of screening procedures must be regulated and standardized, including a combination of assisted visual inspection, cervical cytology and HPV detection; d regional community intervention must be set up to assess the effectiveness of using HPV detection as an strategy in addition to cervical cytology (pap smear; e the practice of colposcopy must be regulated to prevent the use of it in healthy women at a population level, thus preventing unnecessary diagnosis and treatment which not only are expensive but also causes unnecessary anxiety to women at risk; f the operation of those clinical laboratories using HPV as a detection strategy must likewise be accredited and regulated and g the CCSP program for assuring health care quality should meet the expectations of its beneficiaries, and increase the knowledge in cervical cancer related matters. Finally, though a variety of clinical tests on prophylactic and

  13. Impact of stress and levels of corticosterone on the development of breast cancer in rats

    Science.gov (United States)

    De la Roca-Chiapas, José María; Barbosa-Sabanero, Gloria; Martínez-García, Jorge Antonio; Martínez-Soto, Joel; Ramos-Frausto, Víctor Manuel; González-Ramírez, Leivy Patricia; Nowack, Ken

    2016-01-01

    Stress is experienced during cancer, and impairs the immune system’s ability to protect the body. Our aim was to investigate if isolation stress has an impact on the development of tumors in rats, and to measure the size and number of tumors and the levels of corticosterone. Breast cancer was induced in two groups of female rats (N=20) by administration of a single dose of N-methyl-N-nitrosourea 50 mg/kg. Rats in the control group (cancer induction condition) were allowed to remain together in a large cage, whereas in the second group, rats were also exposed to a stressful condition, that is, isolation (cancer induction and isolation condition, CIIC). The CIIC group displayed anxious behavior after 10 weeks of isolation. In the CIIC group, 16 tumors developed, compared with only eleven tumors in the control cancer induction condition group. In addition, compared with the control group, the volume of tumors in the CIIC group was greater, and more rats had more than one tumor and cells showed greater morphological damage. Levels of corticosterone were also significantly different between the two groups. This study supports the hypothesis that stress can influence the development of cancer, but that stress itself is not a sufficient factor for the development of cancer in rats. The study also provides new information for development of experimental studies and controlled environments. PMID:26793009

  14. Breast cancer with different prognostic characteristics developing in Danish women using hormone replacement therapy

    DEFF Research Database (Denmark)

    Stahlberg, Claudia; Pedersen, A T; Andersen, Zorana Jovanovic;

    2004-01-01

    The aim of this study is to investigate the risk of developing prognostic different types of breast cancer in women using hormone replacement therapy (HRT). A total of 10 874 postmenopausal Danish Nurses were followed since 1993. Incident breast cancer cases and histopathological information were...... retrieved through the National Danish registries. The follow-up ended on 31 December 1999. Breast cancer developed in 244 women, of whom 172 were invasive ductal carcinomas. Compared to never users, current users of HRT had an increased risk of a hormone receptor-positive breast cancer, but a neutral risk...... of receptor-negative breast cancer, relative risk (RR) 3.29 (95% confidence interval (CI): 2.27-4.77) and RR 0.99 (95% CI: 0.42-2.36), respectively (P for difference=0.013). The risk of being diagnosed with low histological malignancy grade was higher than high malignancy grade with RR 4.13 (95% CI...

  15. Two cases of colorectal cancer developed more than 30 years after pelvic radiation therapy

    International Nuclear Information System (INIS)

    We experienced two cases of advanced colorectal cancer developed after radiation therapy. One case was a 66-year old female who had received irradiation for her uterine cancer 35 years before. She was treated for a radiation colitis and a radiation dermatitis 6 years ago. Sigmoid colon cancer was pointed out by barium enema and colonoscopy, and Hartmann's operation was performed. The other case was a 68-year old man who had received irradiation for left malignant orchionous 30 years before. He had the radiation dermatitis in both inguinal region, and had received skin graft for the left inguinal dermatitis. He complained of anal bleeding, and rectal cancer was found out by the colonoscopy. Low anterior resection was performed. Their pathological findings showed mucinous adenocarcinoma. In a review of the Japanese literature, colorectal cancers developed more than 30 years after pelvic radiation therapy have been reported in only 8 cases including these two cases. (author)

  16. Radioimmunotherapy of Non-Hodgkin's Lymphoma. The interaction of radiation and antibody with lymphoma cells

    International Nuclear Information System (INIS)

    Whilst many patients with indolent Non-Hodgkin's Lymphoma (NHL) can achieve clinical remissions to first-line chemotherapy and/or radiotherapy, most will relapse. Current treatment options for relapsing patients are limited since most patients become resistant to repeated chemotherapy. Death usually occurs within 10 years of diagnosis. Overall, these disappointing results have not changed significantly in a quarter of a century and clearly advocate the urgent priority to research into potential new therapeutic approaches into this diverse and increasingly prevalent group of human tumours. Radioimmunotherapy (RIT) is currently under investigation as a new approach for the treatment of this disease. In this form of treatment, radionuclide-labeled monoclonal antibodies are able to deliver selective systemic irradiation by recognising tumour-associated antigens. The use of RIT with radiolabeled anti-CD20 antibodies in patients with recurrent B-cell lymphoma has resulted in extremely high rates of durable complete remissions. The optimal approach and mechanisms of action of successful RIT remain however largely unknown. The work described in this thesis has focused on clarifying some of the important determinants and mechanisms of effective RIT of syngeneic B-cell lymphoma, both in vivo and in vitro. A successful animal model of RIT in B cell lymphomas was established by initially generating a panel of antibodies against mouse B cell antigens. The in vitro characteristics of these antibodies have been compared with their subsequent performance, in biodistribution studies and RIT in vivo. For the first time in an in vivo model the relative contributions of antibody and irradiation are described. Some antibodies including anti-MHC Class II were shown to be effective delivery vehicles of low doses of Iodine-131. These antibodies, which appear to be inactive delivery vehicles can cure animals with low burdens of tumour. However antibodies such as anti-idiotype and anti-CD40

  17. Radioimmunotherapy of fungal infection with 213-Bi- and 188-Re-labeled antibody

    International Nuclear Information System (INIS)

    Aim: Radioimmunotherapy (RIT) is a therapeutic modality that utilizes monoclonal antibodies (mAb) radiolabeled with therapeutic radioisotopes to selectively deliver lethal doses of radiation to cells. We hypothesized that 18B7 mAb (murine IgG1), specific for Cryptoccocus neoformans (CN) polysaccharide capsule, may be used to deliver fungicidal doses of radioisotopes to the sites of CN infection in vitro and in vivo. Materials and Methods: 18B7 mAb was radiolabeled with either the beta-emitter 188-Rhenium (188Re) or with the alpha-emitter 213-Bismuth (213Bi). The biodistribution of radiolabeled 18B7 was measured in BALB/c mice with and without intratracheal CN infection. For in vitro killing assays 105 CN cells/well were treated with 0-3.2 μCi 213Bi-18B7 (3 h incubation), 32 μCi 188Re-18B7 (48 h incubation) or with radiolabeled IgG1 MOPC21 as a control and minimal inhibitory concentrations (MIC) were determined. To compare the activity of radiolabeled mAb's against CN infection with an established antifungal drug, we evaluated the susceptibility of CN strain to Amphoterecin B. In vivo therapy of CN was conducted in groups of 10 A/JCr mice infected intravenously with 105 CN cells 24 h prior to treatment with 50-200 μCi 213Bi- or 188Re-18B7, 213Bi- or 188Re-MOPC21, unlabeled 18B7 or saline. Student's t test for unpaired data was used to analyze in vitro data, and log-rank test - for animal survival data. Results: MAb 18B7 preserved its immunoreactivity post-labeling and delivered 10% ID/g to the lungs of the CN-infected BALB/c mice in 24 h after injection. Two-log reduction in colony forming units (CFU) was achieved in treatment of CN with 213Bi-18B7 and 188Re-18B7, which compared favorably with Amphoterecin B. MIC's were determined to be 0.4 μCi/1.5 mg and 4 μCi/1.25 mg mAb for 213Bi-18B7 and 188Re-18B7, respectively. The fungicidal activity of irrelevant mAb 213Bi-or 188Re-MOPC21 was negligible (P213Bi-18B7 and of 100 μCi 188Re-18B7 significantly (P<0

  18. Update on the rational use of tositumomab and iodine-131 tositumomab radioimmunotherapy for the treatment of non-Hodgkin’s lymphoma

    OpenAIRE

    Burdick, Michael J; Macklis, Roger M.

    2009-01-01

    Targeted radioimmunotherapy in non-Hodgkin’s B-cell lymphoma (NHL) offers an efficacious therapy and minimal toxicity compared to conventional chemotherapy. Iodine 131 tositumomab (131I-TST) is a murine monoclonal antibody against the CD20 cell surface protein and is directly covalently conjugated to 131I, a radioactive β and γ emitter. While initially approved for use in relapsed, refractory, or transformed low grade B-cell NHL, investigational uses with promising results include autologous ...

  19. Anti-CD45 Radioimmunotherapy with 90Y but Not 177Lu Is Effective Treatment in a Syngeneic Murine Leukemia Model

    OpenAIRE

    Orozco, Johnnie J.; Ethan R. Balkin; Gooley, Ted A.; Kenoyer, Aimee; Hamlin, Donald K.; Wilbur, D. Scott; Fisher, Darrell R.; Hylarides, Mark D.; Shadman, Mazyar; Green, Damian J.; Gopal, Ajay K.; Press, Oliver W.; Pagel, John M.

    2014-01-01

    Radioimmunotherapy (RIT) for treatment of hematologic malignancies has primarily employed monoclonal antibodies (Ab) labeled with 131I or 90Y which have limitations, and alternative radionuclides are needed to facilitate wider adoption of RIT. We therefore compared the relative therapeutic efficacy and toxicity of anti-CD45 RIT employing 90Y and 177Lu in a syngeneic, disseminated murine myeloid leukemia (B6SJLF1/J) model. Biodistribution studies showed that both 90Y- and 177Lu-anti-murine CD4...

  20. Role of TET enzymes in DNA methylation, development, and cancer

    DEFF Research Database (Denmark)

    Rasmussen, Kasper Dindler; Helin, Kristian

    2016-01-01

    .TETgenes, and especiallyTET2, are frequently mutated in various cancers, but how the TET proteins contribute to prevent the onset and maintenance of these malignancies is largely unknown. Here, we highlight recent advances in understanding the physiological function of the TET proteins and their role in...

  1. [Development of molecular targeted therapies in lung cancers].

    Science.gov (United States)

    Suda, Kenichi; Mitsudomi, Tetsuya

    2014-05-01

    Human cancers usually possess cumulative genetic aberrations. However, recent studies have revealed that the proliferation and survival of specific subsets of lung cancer depend on a few somatic mutation(s), so-called driver mutations. Representative driver mutations include the EGFR mutation and ALK translocation identified in about 40% and 3% of lung adenocarcinomas in Japan, respectively. These tumors are extremely sensitive to the respective tyrosine kinase inhibitors. This sensitivity has encouraged researchers and clinicians to explore novel driver mutations in lung cancers as future molecular targets. Driver mutations reported so far include the HER2 mutation, BRAF mutation, ROS1 translocation, RET translocation, and NTRK translocation in lung adenocarcinomas, and FGFR1 amplification, DDR2 mutation, and FGFR3 translocation in lung squamous cell carcinomas. However, despite initial dramatic responses, the acquisition of resistance to molecular targeted drugs is almost inevitable. Overcoming resistance to molecular targeted drugs, the key drugs at this time, is an urgent issue to improve the outcomes of lung cancer patients. PMID:24946519

  2. miR-10 in development and cancer

    DEFF Research Database (Denmark)

    Lund, Anders Henrik

    2010-01-01

    transcripts. In addition, members of the miR-10 family are de-regulated in several cancer forms. Aside from acting in translational repression, miR-10 was recently found to bind a group of transcripts containing a terminal oligo-pyrimidine (TOP) motif and to induce their translation, thereby adding a new...

  3. Surveillance of Individuals at High Risk for Developing Pancreatic Cancer

    NARCIS (Netherlands)

    F. Harinck (Femme)

    2014-01-01

    markdownabstract__Abstract__ We still face great difficulties to treat and cure patients with pancreatic ductal adenocarcinoma (henceforth referred to as pancreatic cancer). The survival is dismal even in those who undergo intended curative surgery in case of a localized tumor. Despite the relative

  4. Development and evaluation of a support program for prostate cancer survivors in Alaska

    Directory of Open Access Journals (Sweden)

    Stacy Kelley

    2015-11-01

    Full Text Available Background: Prostate cancer survivors in Alaska and elsewhere have unmet support needs. The Men's Prostate Cancer Survivorship Retreat, or “men's retreat,” was developed targeting Alaska Native and non-Native men who were survivors of prostate cancer. The program brought together survivors in a supportive environment to discuss and share their experiences. Objective: Despite the proven effectiveness of support groups for improving quality of life for cancer patients, men typically do not participate in formal support groups. This descriptive study was conducted to explore the needs of Alaska Native and non-Native prostate cancer survivors and assess satisfaction and acceptability of a men's cancer survivorship retreat in Alaska. Methods: Prostate cancer survivors (N=80 who attended men's retreats during 2009–2013 were asked to complete a retreat application and post-retreat evaluation. Comments regarding social support, helpful and valuable aspects of the retreat including overall satisfaction were reported. Results: A men's retreat with activities that engage men can be successful for prostate cancer survivors. Many men returned for successive retreats. After the retreat, 97% of the participants said they would continue with support activities. Conclusion: The men's retreat provides a valued opportunity for men to interact with other survivors and access information from health professionals. The results from this study highlight a successful model for social support and resources specific to male prostate cancer survivors.

  5. Development and Pilot Evaluation of Native CREST – a Cancer Research Experience and Student Training Program for Navajo Undergraduate Students

    OpenAIRE

    Hughes, Christine A; Bauer, Mark C.; Horazdovsky, Bruce F.; Garrison, Edward R.; Patten, Christi A.; Petersen, Wesley O.; Bowman, Clarissa N.; Vierkant, Robert A.

    2013-01-01

    The Mayo Clinic Cancer Center and Diné College received funding for a 4-year collaborative P20 planning grant from the National Cancer Institute in 2006. The goal of the partnership was to increase Navajo undergraduates’ interest in and commitment to biomedical coursework and careers, especially in cancer research. This paper describes the development, pilot testing and evaluation of Native CREST (Cancer Research Experience & Student Training), a 10-week cancer research training program provi...

  6. Association of GSTM1 and GSTT1 deletion with lung cancer development in Pakistani population

    Directory of Open Access Journals (Sweden)

    Nosheen Masood

    2016-01-01

    Conclusion: Results revealed that certain environmental factors may be considered as a risk factor but deletion of GSTM1 and GSTT1 are not associated with the development of lung cancer; however, studies including >500 patient samples is suggested.

  7. The development of an evidence-based physical self-management rehabilitation programme for cancer survivors

    NARCIS (Netherlands)

    van Weert, Ellen; Hoekstra-Weebers, Josette E. H. M.; May, Anne M.; Korstjens, Irene; Ros, Wynand J. G.; van der Schans, Cees P.

    2008-01-01

    Objective: This paper describes the development of a physical training programme for cancer patients. Four related but conceptually and empirically distinct physical problems are described: decreased aerobic capacity, decreased muscle strength, fatigue and impaired role physical functioning. The stu

  8. Macrophage inhibitory cytokine-1 (MIC-1/GDF15 slows cancer development but increases metastases in TRAMP prostate cancer prone mice.

    Directory of Open Access Journals (Sweden)

    Yasmin Husaini

    Full Text Available Macrophage inhibitory cytokine-1 (MIC-1/GDF15, a divergent member of the TGF-β superfamily, is over-expressed by many common cancers including those of the prostate (PCa and its expression is linked to cancer outcome. We have evaluated the effect of MIC-1/GDF15 overexpression on PCa development and spread in the TRAMP transgenic model of spontaneous prostate cancer. TRAMP mice were crossed with MIC-1/GDF15 overexpressing mice (MIC-1(fms to produce syngeneic TRAMP(fmsmic-1 mice. Survival rate, prostate tumor size, histopathological grades and extent of distant organ metastases were compared. Metastasis of TC1-T5, an androgen independent TRAMP cell line that lacks MIC-1/GDF15 expression, was compared by injecting intravenously into MIC-1(fms and syngeneic C57BL/6 mice. Whilst TRAMP(fmsmic-1 survived on average 7.4 weeks longer, had significantly smaller genitourinary (GU tumors and lower PCa histopathological grades than TRAMP mice, more of these mice developed distant organ metastases. Additionally, a higher number of TC1-T5 lung tumor colonies were observed in MIC-1(fms mice than syngeneic WT C57BL/6 mice. Our studies strongly suggest that MIC-1/GDF15 has complex actions on tumor behavior: it limits local tumor growth but may with advancing disease, promote metastases. As MIC-1/GDF15 is induced by all cancer treatments and metastasis is the major cause of cancer treatment failure and cancer deaths, these results, if applicable to humans, may have a direct impact on patient care.

  9. Review of (90Y-ibritumomab tiuxetan as first-line consolidation radio-immunotherapy for B-cell follicular non-Hodgkin’s lymphoma

    Directory of Open Access Journals (Sweden)

    Christos Emmanouilides

    2009-10-01

    Full Text Available Christos EmmanouilidesDepartment of Medical Oncology, Interbalkan Hospital, Thessaloniki, GreeceAbstract: Several studies have indicated that radioimmunotherapy is an effective and clinically relevant complementary therapeutic approach for patients with B-cell non-Hodgkin’s lymphoma (NHL and may convert partial to complete response when given as consolidation after induction chemotherapy. Yttrium-90(90Y-ibritumomab tiuxetan (90Υ-ΙΤ, Zevalin®, Y2B8 has documented efficacy for both indolent and aggressive NHL. Patients considered eligible for 90Y-IT treatment should satisfy several screening criteria. A recently completed randomized study for patients with follicular lymphoma has demonstrated that 90Y-ibritumomab consolidation also produced a marked prolongation of the median time to progression from 13.5 to 37 months, while partial responders seem to derive relatively more benefit. Other published and ongoing studies explore a similar use for patients with aggressive lymphoma. Studies are comparing the use of 90Y-IT consolidation with the anti-CD20 antibody rituximab maintenance, which is also gaining acceptance. In conclusion, the documented benefit of radioimmunotherapy should be viewed in the context of the goals of treatment and the changing standards of care for lymphoma. Keywords: radioimmunotherapy, 90Y-ibritumomab tiuxetan, follicular lymphoma, consolidation

  10. Preliminary report on the clinical application of 131I-chTNT monoclonal antibody radio-immunotherapy in patients with re-operated glioma

    International Nuclear Information System (INIS)

    Objective: To study the safety and therapeutic efficacy of 131I-chTNT monoclonal antibody radio-immunotherapy (RIT) via intratumoral Ommaya reservoir placed during re-operation in patients with glioma. Methods: Twelve patients with recurrent glioma (WHO stage III-IV) underwent second operation(tumor de-bulking) and Ommaya reservoir was placed in the residual cavity. 131I-chimeric tumor necrosis treatment (131I-chTNT) monoclonal antibody 1.5 ml (1110 MBq) was injected into the reservoir as radio-immunotherapy two weeks after the operation and the injection was repeated another two weeks later. Blood chemistry (with hepatic, renal and thyroid functions), brain CT and MR imaging were studied before operation, 3 months and 6 months later. The karnofsky scores were noticed. Results: As shown with the imaging studies, the total treatment response rate was 66.67% (CR 50% and PR 16.67%). General condition was satisfactory and laboratory studies were within normal ranges. There were no serious untoward reactions. Conclusion: Administration of 131I-chTNT monoclonal antibody via Ommaya reservoir as radio-immunotherapy post-operatively was safe and effective in patients with recurrent glioma. The process warranted further study. (authors)

  11. The role of intestinal microflora and probiotic bacteria in prophylactic and development of colorectal cancer

    Directory of Open Access Journals (Sweden)

    Ewa Wasilewska

    2013-08-01

    Full Text Available The gut microbiota comprises a large and diverse range of microorganisms whose activities have a significant impact on health. It interacts with its host at both the local and systemic level, resulting in a broad range of beneficial or detrimental outcomes for nutrition, infections, xenobiotic metabolism, and cancer. The current paper reviews research on the role of intestinal microflora in colorectal cancer development. Especially a protective effect of beneficial bacteria and probiotics on the risk of cancer development is highly discussed. There is substantial experimental evidence that the beneficial gut bacteria and their metabolism have the potential to inhibit the development and progression of neoplasia in the large intestine. Most of the data derive, however, from experimental and animal trials. Over a dozen well-documented animal studies have been published, wherein it has been clearly revealed that some lactic acid bacteria, especially lactobacilli and bifidobacteria, inhibit initiation and progression of colorectal cancer. Studies on cancer suppression in humans as a result of the consumption of probiotics are still sparse. Nevertheless, some epidemiological and interventional studies seem to confirm the bacterial anticancerogenic activity also in human gut. The mechanism by which probiotics may inhibit cancer development is unknown. Probiotics increase the amount of beneficial bacteria and decrease the pathogen level in the gut, consequently altering metabolic, enzymatic and carcinogenic activity in the intestine, decreasing inflammation and enhancing immune function, which may contribute to cancer defense.

  12. Radiotherapy for cancer treatment: A growing priority for developing countries

    International Nuclear Information System (INIS)

    During the 50s Costa Rica started an intensive program of primary health care, because infectious diseases such as diarrhea, parasitosis, tuberculosis and malaria were the main cause of mortality among the population. At that time, the infant mortality rate was 90.2 per 100 live births. Investment in primary care demanded huge economic resources, especially in infrastructure. In 1964, the National Children's Hospital was dedicated. This medical center modified the hospital concept of Costa Rica's pioneers in social security. It joined the existing centers: the San Juan de Dios Hospital (1845) and the Dr. Rafael Angel Calderon Guardia Hospital (1943). In, 1969 the newest national hospital, the Mexico Hospital, was built. The epidemiological profile completely changed: the infant mortality rate dropped, life expectancy at birth increased, and many infectious and parasitic diseases were eliminated. However, there was at the same time an increase in degenerative and cardiovascular diseases, and in cancer. It was not until the 70s, 30 years after the first effort to fight cancer began, that the first cobalt teletherapy unit was purchased to assist cancer patients. This unit was a THERATRON 80, installed at the Mexico Hospital shortly after its opening. In 1975, a campaign to purchase a second cobalt unit was organized. The so-called 'March of One Colon-coin' consisted of voluntarily contributing $0.05 per person. At the end, the goal was reached and the unit was installed at the San Juan de Dios Hospital, in the capital city. With these two cobalt units, plus a third one donated in 1992, Costa Rica was poised to address the radiotherapy needs of its 2 million inhabitants. However, in 1995 a team of physicians of the Calderon Guardia Hospital noted with great concern that despite earlier efforts, mortality associated with the five most frequent cancer types had not decreased. A study of cancer incidence in the country was started. However, just as the study was beginning

  13. Identification of Gene and MicroRNA Signatures for Oral Cancer Developed from Oral Leukoplakia

    OpenAIRE

    Guanghui Zhu; Yuan He; Shaofang Yang; Beimin Chen; Min Zhou; Xin-Jian Xu

    2015-01-01

    In clinic, oral leukoplakia (OLK) may develop into oral cancer. However, the mechanism underlying this transformation is still unclear. In this work, we present a new pipeline to identify oral cancer related genes and microRNAs (miRNAs) by integrating both gene and miRNA expression profiles. In particular, we find some network modules as well as their miRNA regulators that play important roles in the development of OLK to oral cancer. Among these network modules, 91.67% of genes and 37.5% of ...

  14. It's all in the details: methods in breast development and cancer

    OpenAIRE

    Bentires-Alj, Mohamed; Clarke, Robert B.; Jonkers, Jos; Smalley, Matthew; Stein, Torsten

    2009-01-01

    The inaugural European Network for Breast Development and Cancer (ENBDC) meeting on 'Methods in Mammary Gland Development and Cancer' was held in Weggis, Switzerland last April. The goal was to discuss the details of techniques used to study mammary gland biology and tumourigenesis. Highlights of this meeting included the use of four-colour fluorescence for protein co-localisation in tissue microarrays, genome analysis at single cell resolution, technical issues in the isolation of normal and...

  15. Histone deacetylase 1 is required for exocrine pancreatic epithelial proliferation in development and cancer

    OpenAIRE

    Zhou, Weiqiang; Liang, I-Chau; Nelson S. Yee

    2011-01-01

    Histone deacetylases (HDACs) play important roles in the epigenetic control of development and aberrant expression of HDACs has been implicated in human diseases including cancer. Among the mammalian HDACs, HDAC1 has been extensively studied, but its role in exocrine pancreatic morphogenesis and cancer is still poorly understood. The goal of this study is to determine the functional role of HDAC1 in normal development of exocrine pancreas using zebrafish as the model organism as well as in hu...

  16. Treatment of cancer of the uterus in developing countries: Proposals for a programme

    International Nuclear Information System (INIS)

    Cancer of the uterus is one of the most common forms of cancer in developing countries. It may be successfully treated or favourably influenced by intracavitary treatment. For this therapy there are commercially available systems. Three levels of complexity (according to the equipment of the hospital) are recommended for the application of this procedure in the developing countries and the procedure for its introduction is suggested

  17. Psychosocial status of childhood cancer survivors who develop one or more secondary malignancies

    OpenAIRE

    Roman Korenjak; Mojca Čižek Sajko; Berta Jereb

    2011-01-01

    Objective. Childhood cancer survivors can develop physical, emotionaland psychosocial adversities, a secondary malignancy (SM) beingone of the most serious among them. Th e aim of our research was tostudy whether the development of SM was related to the psychosocialfunctioning of survivors, especially whether any psychic trauma fromthe first experience would be aggravated by SM. Patients and methods.Seventy – five childhood cancer survivors with SM were matched with75 survivors who did not de...

  18. Development of botanical principles for clinical use in cancer: Where are we lacking?

    OpenAIRE

    R J Poojari; A G Patil; V S Gota

    2012-01-01

    Development of drugs from plant sources (botanicals) for the treatment of cancer has not been successful in India, despite a plethora of medicinal plants and an equal number of experiments demonstrating anti-cancer activity of plant principles in vitro. There are several pitfalls in our approach to botanical drug development. Foremost is the lack of industry-academia collaborations in this field. Research goals in Indian academic institutions are generally short-term and mostly aimed at fulfi...

  19. Synthesis of chelating agents for actinium 225 complexation and its application in radioimmunotherapy

    International Nuclear Information System (INIS)

    Immunotherapy with radiolabeled antibodies should allow fairly specific targeting of certain cancers. However, iodine 131 may not be the best isotope for tumor therapy because of its limited specific activity, low beta-energy, relatively long half life and strong gamma emission. Another approach to improve therapeutic efficacy is the use of replacement isotopes with better physical properties. Chelator that can hold radio-metals with high stability under physiological conditions are essential to avoid excessive damage to non-target cells; Moreover, the development of new bifunctional chelating agents is essential for this purpose. Accordingly, our efforts have been directed, for several years, to the synthesis of original chelating agents likely to form stable complexes in vivo with the numerous potential candidates for such applications. Therefore, we have developed a new simple and efficient synthesis pathway of 2-(4-iso-thio-cyanate-benzyl)-1,4,7,10,13,16- hexa-aza-cyclo-hexadecane- 1,4,7,10,13,16-hexa-acetic acid, though functionalized on the cycle by a termination allowed coupling to an antibody or any other biological substance such as a hapten. (author)

  20. Development and Validation of a Prediction Model to Estimate Individual Risk of Pancreatic Cancer.

    Directory of Open Access Journals (Sweden)

    Ami Yu

    Full Text Available There is no reliable screening tool to identify people with high risk of developing pancreatic cancer even though pancreatic cancer represents the fifth-leading cause of cancer-related death in Korea. The goal of this study was to develop an individualized risk prediction model that can be used to screen for asymptomatic pancreatic cancer in Korean men and women.Gender-specific risk prediction models for pancreatic cancer were developed using the Cox proportional hazards model based on an 8-year follow-up of a cohort study of 1,289,933 men and 557,701 women in Korea who had biennial examinations in 1996-1997. The performance of the models was evaluated with respect to their discrimination and calibration ability based on the C-statistic and Hosmer-Lemeshow type χ2 statistic.A total of 1,634 (0.13% men and 561 (0.10% women were newly diagnosed with pancreatic cancer. Age, height, BMI, fasting glucose, urine glucose, smoking, and age at smoking initiation were included in the risk prediction model for men. Height, BMI, fasting glucose, urine glucose, smoking, and drinking habit were included in the risk prediction model for women. Smoking was the most significant risk factor for developing pancreatic cancer in both men and women. The risk prediction model exhibited good discrimination and calibration ability, and in external validation it had excellent prediction ability.Gender-specific risk prediction models for pancreatic cancer were developed and validated for the first time. The prediction models will be a useful tool for detecting high-risk individuals who may benefit from increased surveillance for pancreatic cancer.

  1. Cancer, stem cells and cancer stem cells: old ideas, new developments

    OpenAIRE

    Ghaffari, Saghi

    2011-01-01

    It has been suggested that, at least in some forms of cancer, a sub-population of slow-cycling, therapy-resistant cancer stem cells exists that has the ability to reconstitute the tumor in its entirety. If true, this model implies that conventional therapies based on targeting highly cycling cells within the tumor will leave the slow-cycling stem cell population intact, giving them the opportunity to reinitiate the tumor at a later date. This review discusses the evidence for this model and t...

  2. Special event launches new partnership. IAEA and NFCR join forces to fight cancer in developing world

    International Nuclear Information System (INIS)

    Full text: IAEA Director General and Nobel Laureate Mohamed ElBaradei will join more than 100 leading public figures, philanthropists and cancer experts at the United Nations Headquarters in New York on 29 October to mark the launch of a new partnership between the IAEA and the US based National Foundation for Cancer Research (NFCR). Through this partnership, and the endowment fund called the PACT Fund at NFCR, Americans can support the IAEA and its partners in helping poor countries to combat the looming cancer epidemic. 'The IAEA has long provided radiotherapy machines and expertise to developing countries, but the growing cancer crisis cannot be fought with radiotherapy alone,' says Mohamed ElBaradei. 'Our Programme of Action for Cancer Therapy (PACT), which draws on the Agency's long experience in radiation therapy, is building international partnerships to assist in cancer prevention, early detection, treatment and palliative care. Now, through the PACT Fund at NFCR, Americans have the opportunity to support these efforts and bring hope to millions of cancer patients in developing nations.' According to the World Health Organization (WHO), the world is on the brink of a cancer crisis. New cases are expected to double to more than 16 million a year by 2020, unless action is taken now. Hardest hit will be low-income countries, whose health systems are already overburdened by infectious diseases such as HIV/AIDS, Tuberculosis and Malaria. PACT, which was created within the IAEA in 2004, is forging international partnerships with other cancer organizations in both the public and private sectors. Together with partners such as WHO, the American Cancer Society (ACS), the National Cancer Institute (NCI) and the International Agency for Research on Cancer (IARC), it has established pilot projects called Model Demonstration Sites (PMDS) in six countries (Albania, Nicaragua, Sri Lanka, Tanzania, Vietnam and Yemen) to develop and implement comprehensive, integrated

  3. Development of cancer care and use of radiotherapy equipment in a small country - The Finnish model

    International Nuclear Information System (INIS)

    This presentation describes the development of cancer care in Finland focusing on development in the use of radiotherapy and comprehensive QA systems. Finland is a small country in Northern Europe, where health care system has been actively developed to current equal and cost free or low cost treatment for all inhabitants. Radiotherapy, cancer care organizations, screening and awareness of cancer have been systematically developed in Finland since the 1960s. Five university hospitals are responsible for development of diagnostics, treatment and research; The Finnish Cancer Registry is responsible for reliable national statistics on cancer, and through collaboration with other statistical centers for epidemiological and follow up research; The National Radiation and Nuclear Safety Authority (STUK) regulates the use of radiation in Finland. The hospitals must have responsible physicists to maintain suitable instruments and skills to perform high standard quality assurance for the equipment. The Finnish Cancer Society is working on people's awareness and fund raising to support research and rehabilitation. The source for cancer statistics is the population based cancer registry (FCR), which was started in Finland in 1952. The registration of all cancer cases has been mandatory in Finland since the 1960s. Therefore, the currently available data are considered reliable in providing the data on cancer incidences and trends in Finland. Furthermore, the follow up data on treatments, survival and occurrence of new cancer cases among the patients is invaluable for assessing the long term effects of different treatment systems. The Mass Screening Registry is part of the FCR, screening of cervical cancer for 30 to 60 year old women was commenced in the mid 1960s, for 50-59 year old women of breast cancer in the mid 1980s, and screening of colorectal cancer with occult faecal blood tests for 60-69 year old subjects in 2004. Some centres have participated in studies for

  4. Methods in Mammary Gland Development and Cancer: the second ENDBC meeting - intravital imaging, genomics, modeling and metastasis

    OpenAIRE

    Stingl, John; Matthew J Smalley; Glukhova, Marina A.; Bentires-Alj, Mohamed

    2010-01-01

    The second meeting of the European Network for Breast Development and Cancer (ENBDC) on 'Methods in Mammary Gland Development and Cancer' was held in April 2010 in Weggis, Switzerland. The focus was on genomics and bioinformatics, extracellular matrix and stroma-epithelial cell interactions, intravital imaging, the search for metastasis founder cells and mouse models of breast cancer.

  5. Chemoprevention or mastectomy for women at high risk of developing breast cancer.

    Science.gov (United States)

    Sismondi, Piero; D'Alonzo, Marta; Pecchio, Silvia; Bounous, Valentina Elisabetta; Robba, Elisabetta; Biglia, Nicoletta

    2015-11-01

    Breast cancer (BC) is the most commonly diagnosed invasive cancer among women; in developed countries, BC occurs in one out of eight women during her lifetime. Many factors, both genetic and non-genetic, determine a woman's risk of breast cancer and several mathematical models have been proposed that determine the risk. It is important to identify those at high risk, as there are now effective preventive strategies, such as chemoprevention therapy and risk-reduction surgery. Risk-reduction agents are recommended for women aged 35 years or more who are at high risk of breast cancer. Tamoxifen is presently deemed to be the agent of choice. However, raloxifene may be preferable, at least for some postmenopausal women, because of its lack of effect on the endometrium and the reduced incidence of venous thromboembolic events compared with tamoxifen. Prophylactic surgery has been widely investigated. Bilateral mastectomy decreases the risk of developing breast cancer by approximately 90% in women at moderate or high risk and in known BRCA1/2 mutation carriers. This review summarizes the recent advances in the identification of women at high risk of developing breast cancer and reports on the strategies used to prevent breast cancer; the risk-benefit balance of such preventive choices is also briefly analyzed. PMID:26276104

  6. Indigenous development of integrated medical Linac system for cancer therapy - Jai Vigyan programme

    International Nuclear Information System (INIS)

    6 MV integrated medical LINAC system was developed for cancer therapy jointly by CSIR-CSIO Chandigarh and SAMEER Mumbai under the Jai Vigyan Programme of the Government of India. Six machines were originally planned to be commissioned in six cancer hospitals in the country. Two machines, namely SIDDARTH I and SIDDARTH II, have already been developed and deployed at MGIMS, Sevagram, Wardha (Maharashtra) and at Cancer Institute (WIA), Adyar, Chennai. These machines are working satisfactorily since their installation. Four more machines namely SIDDARTH III-IV, are underway which will be commissioned in four national cancer institutes by the end of next year. This paper describes in brief the scientific principles of LINAC machines and technological challenges involved in the design and development of such a system of multi-disciplinary activities. (author)

  7. Design elements for the development of cancer education print materials for a Latina/o audience.

    Science.gov (United States)

    Buki, Lydia P; Salazar, Silvia I; Pitton, Viviana O

    2009-10-01

    Health educators can help reduce cancer disparities in Latino populations through the creation of effective print materials. In this effort, the National Cancer Institute conducted a comprehensive needs assessment to identify key design elements of cancer education programs and create a cost-effective process that would ensure consistency in the development of materials. This article introduces the Checklist of Design Elements for the Development of Cancer Education Print Materials for Latina/o Audiences (CEMLA), which includes a total of 10 design elements related to the process of developing materials and content. Using social learning theory as a theoretical framework, design elements are included that reflect cultural sensitivity at the surface and deep structure levels. This is the most comprehensive effort to date to integrate and synthesize theory and application in the design of materials for this audience. PMID:19098265

  8. The role of NANOG transcriptional factor in the development of malignant phenotype of cancer cells.

    Science.gov (United States)

    Gawlik-Rzemieniewska, Natalia; Bednarek, Ilona

    2016-01-01

    NANOG is a transcription factor that is involved in the self-renewal of embryonic stem cells (ES) and is a critical factor for the maintenance of the undifferentiated state of pluripotent cells. Extensive data in the literature show that the NANOG gene is aberrantly expressed during the development of malignancy in cancer cells. ES and cancer stem cells (CSCs), a subpopulation of cancer cells within the tumor, are thought to share common phenotypic properties. This review describes the role of NANOG in cancer cell proliferation, epithelial-mesenchymal transition (EMT), apoptosis and metastasis. In addition, this paper illustrates a correlation between NANOG and signal transducer and activator of transcription 3 (STAT3) in the maintenance of cancer stem cell properties and multidrug resistance. Together, the available data demonstrate that NANOG is strictly involved in the process of carcinogenesis and is a potential prognostic marker of malignant tumors. PMID:26618281

  9. Development of a distress inventory for cancer: preliminary results.

    OpenAIRE

    Thomas B; Mohan V; Thomas I; Pandey M

    2002-01-01

    CONTEXT: Advances in cancer treatment have led to cure and prolongation of patients′ lives; however associated psychosocial problems, including distress, can detrimentally affect patients′ compliance with treatment and ultimately, their outcome. Symptom distress has been well addressed in many studies; however, psychological distress has only been quantified by using depression or anxiety scales/checklists or quality of life scales containing a distress sub scale/component or by...

  10. The role of chromosome missegregation in cancer development: a theoretical approach using agent-based modelling.

    Directory of Open Access Journals (Sweden)

    Arturo Araujo

    Full Text Available Many cancers are aneuploid. However, the precise role that chromosomal instability plays in the development of cancer and in the response of tumours to treatment is still hotly debated. Here, to explore this question from a theoretical standpoint we have developed an agent-based model of tissue homeostasis in which to test the likely effects of whole chromosome mis-segregation during cancer development. In stochastic simulations, chromosome mis-segregation events at cell division lead to the generation of a diverse population of aneuploid clones that over time exhibit hyperplastic growth. Significantly, the course of cancer evolution depends on genetic linkage, as the structure of chromosomes lost or gained through mis-segregation events and the level of genetic instability function in tandem to determine the trajectory of cancer evolution. As a result, simulated cancers differ in their level of genetic stability and in their growth rates. We used this system to investigate the consequences of these differences in tumour heterogeneity for anti-cancer therapies based on surgery and anti-mitotic drugs that selectively target proliferating cells. As expected, simulated treatments induce a transient delay in tumour growth, and reveal a significant difference in the efficacy of different therapy regimes in treating genetically stable and unstable tumours. These data support clinical observations in which a poor prognosis is correlated with a high level of chromosome mis-segregation. However, stochastic simulations run in parallel also exhibit a wide range of behaviours, and the response of individual simulations (equivalent to single tumours to anti-cancer therapy prove extremely variable. The model therefore highlights the difficulties of predicting the outcome of a given anti-cancer treatment, even in cases in which it is possible to determine the genotype of the entire set of cells within the developing tumour.

  11. Targeting autophagy in cancer management – strategies and developments

    Directory of Open Access Journals (Sweden)

    Ozpolat B

    2015-09-01

    Full Text Available Bulent Ozpolat,1 Doris M Benbrook2 1Department of Experimental Therapeutics, The University of Texas – Houston, MD Anderson Cancer Center, Houston, TX, 2Department of Obstetrics and Gynecology, University of Oklahoma HSC, Oklahoma City, OK, USA Abstract: Autophagy is a highly regulated catabolic process involving lysosomal degradation of intracellular components, damaged organelles, misfolded proteins, and toxic aggregates, reducing oxidative stress and protecting cells from damage. The process is also induced in response to various conditions, including nutrient deprivation, metabolic stress, hypoxia, anticancer therapeutics, and radiation therapy to adapt cellular conditions for survival. Autophagy can function as a tumor suppressor mechanism in normal cells and dysregulation of this process (ie, monoallelic Beclin-1 deletion may lead to malignant transformation and carcinogenesis. In tumors, autophagy is thought to promote tumor growth and progression by helping cells to adapt and survive in metabolically-challenged and harsh tumor microenvironments (ie, hypoxia and acidity. Recent in vitro and in vivo studies in preclinical models suggested that modulation of autophagy can be used as a therapeutic modality to enhance the efficacy of conventional therapies, including chemo and radiation therapy. Currently, more than 30 clinical trials are investigating the effects of autophagy inhibition in combination with cytotoxic chemotherapies and targeted agents in various cancers. In this review, we will discuss the role, molecular mechanism, and regulation of autophagy, while targeting this process as a novel therapeutic modality, in various cancers. Keywords: autophagy inhibition, chemotherapy, tumor microenvironment

  12. Ixabepilone development across the breast cancer continuum: a paradigm shift

    International Nuclear Information System (INIS)

    The epothilone analog ixabepilone exhibits reduced susceptibility to several important tumor survival mechanisms that limit the efficacy of taxanes and anthracyclines. As a single agent, ixabepilone has shown promise in metastatic breast cancer when anthracyclines, taxanes, or capecitabine have failed; and in early-stage breast cancer that is taxane-naïve or has previously received taxanes in the adjuvant or metastatic setting. Compared with capecitabine alone, ixabepilone used in combination with capecitabine in patients previously treated with and resistant to anthracyclines and taxanes produced a 25% reduction in the risk of disease progression. Triple-negative tumors showed particular susceptibility to this doublet. Ixabepilone has also demonstrated efficacy as first-line therapy in combination with targeted agents such as bevacizumab and trastuzumab. Ongoing investigations should provide insight as to how this agent could be integrated into treatment of early-stage disease. In clinical studies, toxicities with ixabepilone were manageable and reversible through dose reduction or delay, even in patients with extensive or heavily-pretreated disease. Thus, ixabepilone represents a useful addition to the therapeutic options available for advanced breast cancer, and it may extend progression-free survival in patients with limited treatment options

  13. PERK Integrates Oncogenic Signaling and Cell Survival During Cancer Development.

    Science.gov (United States)

    Bu, Yiwen; Diehl, J Alan

    2016-10-01

    Unfolded protein responses (UPR), consisting of three major transducers PERK, IRE1, and ATF6, occur in the midst of a variety of intracellular and extracellular challenges that perturb protein folding in the endoplasmic reticulum (ER). ER stress occurs and is thought to be a contributing factor to a number of human diseases, including cancer, neurodegenerative disorders, and various metabolic syndromes. In the context of neoplastic growth, oncogenic stress resulting from dysregulation of oncogenes such as c-Myc, Braf(V600E) , and HRAS(G12V) trigger the UPR as an adaptive strategy for cancer cell survival. PERK is an ER resident type I protein kinase harboring both pro-apoptotic and pro-survival capabilities. PERK, as a coordinator through its downstream substrates, reprograms cancer gene expression to facilitate survival in response to oncogenes and microenvironmental challenges, such as hypoxia, angiogenesis, and metastasis. Herein, we discuss how PERK kinase engages in tumor initiation, transformation, adaption microenvironmental stress, chemoresistance and potential opportunities, and potential opportunities for PERK targeted therapy. J. Cell. Physiol. 231: 2088-2096, 2016. © 2016 Wiley Periodicals, Inc. PMID:26864318

  14. The Kanker Nazorg Wijzer (Cancer Aftercare Guide) protocol: the systematic development of a web-based computer tailored intervention providing psychosocial and lifestyle support for cancer survivors

    OpenAIRE

    Willems, Roy A; Bolman, Catherine AW; Mesters, Ilse; Kanera, Iris M.; Beaulen, Audrey AJM; Lechner, Lilian

    2015-01-01

    Background After primary treatment, many cancer survivors experience psychosocial, physical, and lifestyle problems. To address these issues, we developed a web-based computer tailored intervention, the Kanker Nazorg Wijzer (Cancer Aftercare Guide), aimed at providing psychosocial and lifestyle support for cancer survivors. The purpose of this article is to describe the systematic development and the study design for evaluation of this theory and empirical based intervention. Methods/design F...

  15. Development of cancer-initiating cells and immortalized cells with genomic instability.

    Science.gov (United States)

    Yoshioka, Ken-Ichi; Atsumi, Yuko; Nakagama, Hitoshi; Teraoka, Hirobumi

    2015-03-26

    Cancers that develop after middle age usually exhibit genomic instability and multiple mutations. This is in direct contrast to pediatric tumors that usually develop as a result of specific chromosomal translocations and epigenetic aberrations. The development of genomic instability is associated with mutations that contribute to cellular immortalization and transformation. Cancer occurs when cancer-initiating cells (CICs), also called cancer stem cells, develop as a result of these mutations. In this paper, we explore how CICs develop as a result of genomic instability, including looking at which cancer suppression mechanisms are abrogated. A recent in vitro study revealed the existence of a CIC induction pathway in differentiating stem cells. Under aberrant differentiation conditions, cells become senescent and develop genomic instabilities that lead to the development of CICs. The resulting CICs contain a mutation in the alternative reading frame of CDKN2A (ARF)/p53 module, i.e., in either ARF or p53. We summarize recently established knowledge of CIC development and cellular immortality, explore the role of the ARF/p53 module in protecting cells from transformation, and describe a risk factor for genomic destabilization that increases during the process of normal cell growth and differentiation and is associated with the downregulation of histone H2AX to levels representative of growth arrest in normal cells. PMID:25815132

  16. Effects of Honey and Its Mechanisms of Action on the Development and Progression of Cancer

    Directory of Open Access Journals (Sweden)

    Omotayo O. Erejuwa

    2014-02-01

    Full Text Available Honey is a natural product known for its varied biological or pharmacological activities—ranging from anti-inflammatory, antioxidant, antibacterial, antihypertensive to hypoglycemic effects. This review article focuses on the role of honey in modulating the development and progression of tumors or cancers. It reviews available evidence (some of which is very recent with regards to the antimetastatic, antiproliferative and anticancer effects of honey in various forms of cancer. These effects of honey have been thoroughly investigated in certain cancers such as breast, liver and colorectal cancer cell lines. In contrast, limited but promising data are available for other forms of cancers including prostate, bladder, endometrial, kidney, skin, cervical, oral and bone cancer cells. The article also underscores the various possible mechanisms by which honey may inhibit growth and proliferation of tumors or cancers. These include regulation of cell cycle, activation of mitochondrial pathway, induction of mitochondrial outer membrane permeabilization, induction of apoptosis, modulation of oxidative stress, amelioration of inflammation, modulation of insulin signaling and inhibition of angiogenesis. Honey is highly cytotoxic against tumor or cancer cells while it is non-cytotoxic to normal cells. The data indicate that honey can inhibit carcinogenesis by modulating the molecular processes of initiation, promotion, and progression stages. Thus, it may serve as a potential and promising anticancer agent which warrants further experimental and clinical studies.

  17. Risk factors for skin cancer development in patients after organ transplantation 

    Directory of Open Access Journals (Sweden)

    Beata Imko-Walczuk

    2012-11-01

    Full Text Available Cancer has become the second most common cause of death in patients after organ transplantation. Among all cancers arising de novo after transplantation skin cancers are the most common, accounting for 95�0of all skin neoplasms.Due to the significantly higher morbidity, aggressive, rapid progression of cancer and unfavorable prognosis, the population requires a specific oncological approach. Therefore, special attention should be paid to factors predisposing to the development of cancer, including skin cancer, in patients after organ transplantation. Some of these factors are well understood, while the role of others is still ambiguous. Among the etiological factors mentioned are those that are associated with the recipient. These include genetic factors such as male sex, fair skin and inability to be tanned, and compatibility of the HLA system, and non genetic factors such as patient age, chronic skin ulcers and scars, the type of transplanted organ, immunosuppression, and particularly the type and cumulative doses of drugs. In addition, the pathogenesis of cancer is influenced by environmental factors such as exposure to sunlight and therefore latitude, ionizing radiation, chemical carcinogens and viral infections.Knowledge of etiological factors and mechanisms of etiopathogenesis allow for indication and observation of patients with increased risk of cancer as well as faster healing in these patients. 

  18. Development of the M. D. Anderson Cancer Center Gynecologic Applicators for the Treatment of Cervical Cancer: Historical Analysis

    International Nuclear Information System (INIS)

    Purpose: To provide historical background on the development and initial studies of the gynecological (gyn) applicators developed by Dr. Gilbert H. Fletcher, a radiation oncologist and chairperson from 1948 to 1981 of the department at the M.D. Anderson Hospital (MDAH) for Cancer Research in Houston, TX, and to acknowledge the previously unrecognized contribution that Dr. Leonard G. Grimmett, a radiation physicist and chairperson from 1949 to 1951 of the physics department at MDAH, made to the development of the gynecological applicators. Methods and Materials: We reviewed archival materials from the Historical Resource Center and from the Department of Radiation Physics at University of Texas M. D. Anderson Cancer Center, as well as contemporary published papers, to trace the history of the applicators. Conclusions: Dr. Fletcher’s work was influenced by the work on gynecologic applicators in the 1940s in Europe, especially work done at the Royal Cancer Hospital in London. Those efforts influenced not only Dr. Fletcher’s approach to the design of the applicators but also the methods used to perform in vivo measurements and determine the dose distribution. Much of the initial development of the dosimetry techniques and measurements at MDAH were carried out by Dr. Grimmett.

  19. Improving quality of breast cancer surgery through development of a national breast cancer surgical outcomes (BRCASO research database

    Directory of Open Access Journals (Sweden)

    Aiello Bowles Erin J

    2012-04-01

    Full Text Available Abstract Background Common measures of surgical quality are 30-day morbidity and mortality, which poorly describe breast cancer surgical quality with extremely low morbidity and mortality rates. Several national quality programs have collected additional surgical quality measures; however, program participation is voluntary and results may not be generalizable to all surgeons. We developed the Breast Cancer Surgical Outcomes (BRCASO database to capture meaningful breast cancer surgical quality measures among a non-voluntary sample, and study variation in these measures across providers, facilities, and health plans. This paper describes our study protocol, data collection methods, and summarizes the strengths and limitations of these data. Methods We included 4524 women ≥18 years diagnosed with breast cancer between 2003-2008. All women with initial breast cancer surgery performed by a surgeon employed at the University of Vermont or three Cancer Research Network (CRN health plans were eligible for inclusion. From the CRN institutions, we collected electronic administrative data including tumor registry information, Current Procedure Terminology codes for breast cancer surgeries, surgeons, surgical facilities, and patient demographics. We supplemented electronic data with medical record abstraction to collect additional pathology and surgery detail. All data were manually abstracted at the University of Vermont. Results The CRN institutions pre-filled 30% (22 out of 72 of elements using electronic data. The remaining elements, including detailed pathology margin status and breast and lymph node surgeries, required chart abstraction. The mean age was 61 years (range 20-98 years; 70% of women were diagnosed with invasive ductal carcinoma, 20% with ductal carcinoma in situ, and 10% with invasive lobular carcinoma. Conclusions The BRCASO database is one of the largest, multi-site research resources of meaningful breast cancer surgical quality data

  20. Improving quality of breast cancer surgery through development of a national breast cancer surgical outcomes (BRCASO) research database

    International Nuclear Information System (INIS)

    Common measures of surgical quality are 30-day morbidity and mortality, which poorly describe breast cancer surgical quality with extremely low morbidity and mortality rates. Several national quality programs have collected additional surgical quality measures; however, program participation is voluntary and results may not be generalizable to all surgeons. We developed the Breast Cancer Surgical Outcomes (BRCASO) database to capture meaningful breast cancer surgical quality measures among a non-voluntary sample, and study variation in these measures across providers, facilities, and health plans. This paper describes our study protocol, data collection methods, and summarizes the strengths and limitations of these data. We included 4524 women ≥18 years diagnosed with breast cancer between 2003-2008. All women with initial breast cancer surgery performed by a surgeon employed at the University of Vermont or three Cancer Research Network (CRN) health plans were eligible for inclusion. From the CRN institutions, we collected electronic administrative data including tumor registry information, Current Procedure Terminology codes for breast cancer surgeries, surgeons, surgical facilities, and patient demographics. We supplemented electronic data with medical record abstraction to collect additional pathology and surgery detail. All data were manually abstracted at the University of Vermont. The CRN institutions pre-filled 30% (22 out of 72) of elements using electronic data. The remaining elements, including detailed pathology margin status and breast and lymph node surgeries, required chart abstraction. The mean age was 61 years (range 20-98 years); 70% of women were diagnosed with invasive ductal carcinoma, 20% with ductal carcinoma in situ, and 10% with invasive lobular carcinoma. The BRCASO database is one of the largest, multi-site research resources of meaningful breast cancer surgical quality data in the United States. Assembling data from electronic

  1. Multifunctional DDX3: dual roles in various cancer development and its related signaling pathways

    Science.gov (United States)

    Zhao, Luqing; Mao, Yitao; Zhou, Jianhua; Zhao, Yuelong; Cao, Ya; Chen, Xiang

    2016-01-01

    DEAD-box RNA helicase 3 (DDX3) is a highly conserved family member of DEAD-box protein, which is a cluster of ATP-dependent and the largest family of RNA helicase. DEAD-box family is characterized by the regulation of ATPase and helicase activities, the modulation of RNA metabolism, and the actors of RNA binding proteins or molecular chaperones to interact with other proteins or RNA. For DDX3, it exerts its multifaceted roles in viral manipulation, stress response, hypoxia, radiation response and apoptosis, and is closely related to cancer development and progression. DDX3 has dual roles in different cancer types and can act as either an oncogene or tumor suppressor gene during cancer progression. In the present review, we mainly provide an overview of current knowledge on dual roles of DDX3 in various types of cancer, including breast cancer, lung cancer, colorectal cancer, hepatocellular carcinoma, oral squamous cell carcinoma, Ewing sarcoma, glioblastoma multiforme and gallbladder carcinoma, and illustrate the regulatory mechanisms for leading these two controversial biological effects. Furthermore, we summarize the essential signaling pathways that DDX3 participated, especially the Wnt/β-catenin signaling and EMT related signaling (TGF-β, Notch, Hedgehog pathways), which are crucial to DDX3 mediated cancer metastasis process. Thoroughly exploring the dual roles of DDX3 in cancer development and the essential signaling pathways it involved, it will help us open new perspectives to develop novel promising targets to elevate therapeutic effects and facilitate the “Personalized medicine” or “Precision medicine” to come into clinic.

  2. Impact of stress and levels of corticosterone on the development of breast cancer in rats

    Directory of Open Access Journals (Sweden)

    De la Roca-Chiapas JM

    2016-01-01

    Full Text Available José María De la Roca-Chiapas,1 Gloria Barbosa-Sabanero,2 Jorge Antonio Martínez-García,3 Joel Martínez-Soto,1 Víctor Manuel Ramos-Frausto,1 Leivy Patricia González-Ramírez,1 Ken Nowack4 1Department of Psychology, 2Department of Medical Sciences, Division of Health Sciences, Campus Leon-University of Guanajuato, Guanajuato, 3General Regional Hospital of Leon, Guanajuato, Mexico; 4Envisia Learning, Inc., Santa Monica, CA, USA Abstract: Stress is experienced during cancer, and impairs the immune system's ability to protect the body. Our aim was to investigate if isolation stress has an impact on the development of tumors in rats, and to measure the size and number of tumors and the levels of corticosterone. Breast cancer was induced in two groups of female rats (N=20 by administration of a single dose of N-methyl-N-nitrosourea 50 mg/kg. Rats in the control group (cancer induction condition were allowed to remain together in a large cage, whereas in the second group, rats were also exposed to a stressful condition, that is, isolation (cancer induction and isolation condition, CIIC. The CIIC group displayed anxious behavior after 10 weeks of isolation. In the CIIC group, 16 tumors developed, compared with only eleven tumors in the control cancer induction condition group. In addition, compared with the control group, the volume of tumors in the CIIC group was greater, and more rats had more than one tumor and cells showed greater morphological damage. Levels of corticosterone were also significantly different between the two groups. This study supports the hypothesis that stress can influence the development of cancer, but that stress itself is not a sufficient factor for the development of cancer in rats. The study also provides new information for development of experimental studies and controlled environments. Keywords: breast cancer, corticosterone, isolation condition, psychoneuroimmunology, stress

  3. Current Challenges in Development of Differentially Expressed and Prognostic Prostate Cancer Biomarkers

    Directory of Open Access Journals (Sweden)

    Steven M. Lucas

    2012-01-01

    Full Text Available Introduction. Predicting the aggressiveness of prostate cancer at biopsy is invaluable in making treatment decisions. In this paper we review the differential expression of genes and microRNAs identified through microarray analysis as potentially useful markers for prostate cancer prognosis and discuss some of the challenges associated with their development. Methods. A review of the literature was conducted through Medline. Articles were identified through searches of the following terms: “prostate cancer AND differential expression”, “prostate cancer prognosis”, and “prostate cancer AND microRNAs”. Results. Though numerous differentially expressed genes and microRNAs were identified as possible prognostic markers, the significance of several of these genes is either debated due to conflicting results or is not validated in other study populations. A few of the articles constructed predictive nomograms using a panel of biomarkers which require further validation. Challenges to the development of useful markers include different methodology, cancer heterogeneity, and sampling error. These can be overcome by categorizing prognostic factors into particular gene pathways or by supplementing biopsy information with blood or urine-based biomarkers. Conclusion. Though biomarkers based on differential expression offer the potential to improve decision making concerning prostate cancer, further validation of their utility and accuracy at the biopsy level is needed.

  4. Novel compounds in the treatment of lung cancer: current and developing therapeutic agents

    Science.gov (United States)

    Bao, Rudi; Chan, Pokman

    2011-01-01

    Lung cancer is the leading cause of cancer-related death in the United States. Though incremental advances have been made in the treatment of this devastating disease during the past decade, new therapies are urgently needed. Traditional cytotoxic agents have been combined with other modalities with improved survival for early-stage patients. Newer cytotoxic agents targeting the same or different mechanisms have been developed at different stages. Optimization of various chemotherapy regimens in different settings is one of the aims of current clinical trials. Some predictive biomarkers (eg, excision repair cross-complementing 1, ERCC1) and histotypes (eg, adenocarcinoma) are found to be associated with resistance/response to some cytotoxic drugs. Another notable advance is the addition of targeted therapy to lung cancer treatment. Targeted agents such as erlotinib and bevacizumab have demonstrated clinical benefits and gained Food and Drug Administration approval for lung cancer. More agents targeting various signaling pathways critical to lung cancer are at different stages of development. Along with the effort of new targeted drug discovery, biomarkers such as epidermal growth factor receptor and anaplastic lymphoma kinase mutations have proven useful for patient selection, and more predictive biomarkers have been actively evaluated in non-small cell lung cancer. The paradigm of lung cancer treatment has shifted towards biomarker-based personalized medicine.

  5. Development of an Oncolytic Adenovirus with Enhanced Spread Ability through Repeated UV Irradiation and Cancer Selection.

    Science.gov (United States)

    Wechman, Stephen L; Rao, Xiao-Mei; Cheng, Pei-Hsin; Gomez-Gutierrez, Jorge G; McMasters, Kelly M; Zhou, H Sam

    2016-01-01

    Oncolytic adenoviruses (Ads) have been shown to be safe and have great potential for the treatment of solid tumors. However, the therapeutic efficacy of Ads is antagonized by limited spread within solid tumors. To develop Ads with enhanced spread, viral particles of an E1-wildtype Ad5 dl309 was repeatedly treated with UV type C irradiation and selected for the efficient replication and release from cancer cells. After 72 cycles of treatment and cancer selection, AdUV was isolated. This vector has displayed many favorable characteristics for oncolytic therapy. AdUV was shown to lyse cancer cells more effectively than both E1-deleted and E1-wildtype Ads. This enhanced cancer cell lysis appeared to be related to increased AdUV replication in and release from infected cancer cells. AdUV-treated A549 cells displayed greater expression of the autophagy marker LC3-II during oncolysis and formed larger viral plaques upon cancer cell monolayers, indicating increased virus spread among cancer cells. This study indicates the potential of this approach of irradiation of entire viral particles for the development of oncolytic viruses with designated therapeutic properties. PMID:27314377

  6. Development of an Oncolytic Adenovirus with Enhanced Spread Ability through Repeated UV Irradiation and Cancer Selection

    Directory of Open Access Journals (Sweden)

    Stephen L. Wechman

    2016-06-01

    Full Text Available Oncolytic adenoviruses (Ads have been shown to be safe and have great potential for the treatment of solid tumors. However, the therapeutic efficacy of Ads is antagonized by limited spread within solid tumors. To develop Ads with enhanced spread, viral particles of an E1-wildtype Ad5 dl309 was repeatedly treated with UV type C irradiation and selected for the efficient replication and release from cancer cells. After 72 cycles of treatment and cancer selection, AdUV was isolated. This vector has displayed many favorable characteristics for oncolytic therapy. AdUV was shown to lyse cancer cells more effectively than both E1-deleted and E1-wildtype Ads. This enhanced cancer cell lysis appeared to be related to increased AdUV replication in and release from infected cancer cells. AdUV-treated A549 cells displayed greater expression of the autophagy marker LC3-II during oncolysis and formed larger viral plaques upon cancer cell monolayers, indicating increased virus spread among cancer cells. This study indicates the potential of this approach of irradiation of entire viral particles for the development of oncolytic viruses with designated therapeutic properties.

  7. Bioinformatic Screening of Key Genes Controlling the Development 
and Progression of Lung Cancer

    Directory of Open Access Journals (Sweden)

    Junlong WANG

    2012-11-01

    Full Text Available Background and objective Lung cancer is the most common cancer in the world. The gene expression profiling of lung cancer has been extensively investigated. However, only a few studies have identified the possible pathways and significant genes related to lung cancer. The aim of this study is to explore the large number of lung cancer-related microarray datasets and identify the crucial genes that can benefit the understanding of the progression and development of this disease. Methods To identify the genes that effected lung cancer at the mRNA level, gene set enrichment analysis was used to analyze six selected gene expression datasets. Results Among the six gene expression datasets, 3 up-regulated and 26 down-regulated pathways were found by gene set enrichment analysis. We found 11 significant genes with P<0.05 from the results of tight junction meta-analysis of the six data sets. Conclusion The tight junction pathway plays an important role in the study of the occurrence and development of lung cancer. Significant genes within the pathways will be further discussed in future studies.

  8. SALL4, the missing link between stem cells, development and cancer.

    Science.gov (United States)

    Tatetsu, Hiro; Kong, Nikki R; Chong, Gao; Amabile, Giovanni; Tenen, Daniel G; Chai, Li

    2016-06-15

    There is a growing body of evidence supporting that cancer cells share many similarities with embryonic stem cells (ESCs). For example, aggressive cancers and ESCs share a common gene expression signature that includes hundreds of genes. Since ESC genes are not present in most adult tissues, they could be ideal candidate targets for cancer-specific diagnosis and treatment. This is an exciting cancer-targeting model. The major hurdle to test this model is to identify the key factors/pathway(s) within ESCs that are responsible for the cancer phenotype. SALL4 is one of few genes that can establish this link. The first publication of SALL4 is on its mutation in a human inherited disorder with multiple developmental defects. Since then, over 300 papers have been published on various aspects of this gene in stem cells, development, and cancers. This review aims to summarize our current knowledge of SALL4, including a SALL4-based approach to classify and target cancers. Many questions about this important gene still remain unanswered, specifically, on how this gene regulates cell fates at a molecular level. Understanding SALL4's molecular functions will allow development of specific targeted approaches in the future. PMID:26892498

  9. Cancer

    Science.gov (United States)

    ... Blood tests (which look for chemicals such as tumor markers) Bone marrow biopsy (for lymphoma or leukemia) Chest ... the case with skin cancers , as well as cancers of the lung, breast, and colon. If the tumor has spread ...

  10. Cancer

    Science.gov (United States)

    Cancer begins in your cells, which are the building blocks of your body. Normally, your body forms ... be benign or malignant. Benign tumors aren't cancer while malignant ones are. Cells from malignant tumors ...

  11. Development, implementation and evaluation of a multidisciplinary cancer rehabilitation programme : The CANSURVIVOR Project : meeting post-treatment cancer survivors’ needs

    LENUS (Irish Health Repository)

    Ivers, Mary E.

    2009-01-01

    Cancer survivor numbers in Ireland are increasing due to the success of modern treatments. Although most survivors have a good quality of life not all survivors return to \\'normal\\' after treatment. The HSE funded CANSURVIVOR research project has found that many survivors have difficulties and need help to recover and adjust after cancer treatment. Over a number of exploratory studies using interviews, focus groups and a survey of 262 breast, prostate, colorectal and lung cancer survivors, the researchers found that over 25% of survivors experienced significant difficulties with physical, emotional and social functioning, including symptoms such as insomnia and fatigue, while 33% experienced high levels of anxiety. Of particular concern were the findings that over 50% of survivors were overweight, 35% had reduced their physical activity levels and 13% continued to smoke after cancer, putting them at risk for further health problems. This evidence led to the development of an 8-week multi-disciplinary pilot rehabilitation programme. Significant quality of life improvements were achieved with increases in strength and fitness as well as a reduction in anxiety levels and dietary improvements. The researchers highlight the need for a structured, co-ordinated survivorship service, education of health professionals about survivorship and the provision of high quality information to survivors. This research was led by the School of Psychology at UCD in collaboration with the Physiotherapy and Nutrition departments of St. Vincent\\'s hospital.

  12. Development of Therapeutic Modality of Esophageal Cancer Using Ho-166 Stent

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Jong Doo; Park, Kwang Kyun; Lee, Min Geol [Yonsei University Medical College, Seoul (Korea, Republic of); Park, Kyung Bae [Korea Atomic Energy Research Institute, Taejon (Korea, Republic of)

    1997-09-01

    The prognosis of esophageal cancer is poor due absence of serosa which prevent local invasion to the surrounding organs such as aorta, mediastinum, trachea, and bronchi. We developed a Ho-166 Coated Radioactive Self-Expandable Metallic Stent which is a new herapeutic device in the treatment of esophageal cancer and underwent an animal experiment in mongrel dogs. We observed mucosal destruction by 4-6 mCi of Ho-166 without serious complications such as perforation of esophageal wall. Therefore, Ho-166 coated self-expandable stent appears to be an effective therapeutic device in the palliative treatment of esophageal cancer. 17 refs., 4 figs. (author)

  13. Development of the Fibulin-3 protein therapeutics of non small cell lung cancer stem cells

    International Nuclear Information System (INIS)

    This study focuses on developing an efficient bioprocess for large-scale production of fibulin-3 using Chinese Hamster Ovary cell expression system and evaluating its therapeutic potential for the treatment of cancer. The specific aims are as follows: Isolation and establishment of CSCs using FACS based on cell surface markers and high ALDH1 activity. Identification and characterization of lung cancer stem cells that acquire features of CSC upon exposure to ionizing radiation. Evaluation of the fibulin-3 effects on the stem traits and signaling pathways required for the generation and maintenance of CSCs. In vivo validation of fivulin-3 for tumor prognosis and therapeutic efficacy against lung cancer using animal model

  14. Development of the Fibulin-3 protein therapeutics of non small cell lung cancer stem cells

    Energy Technology Data Exchange (ETDEWEB)

    Kim, In Gyu; Kim, Kugchan; Jung, Il Lae; Kim, Seo Yeon; Choi, Su Im; Lee, Jae Ha

    2013-09-15

    This study focuses on developing an efficient bioprocess for large-scale production of fibulin-3 using Chinese Hamster Ovary cell expression system and evaluating its therapeutic potential for the treatment of cancer. The specific aims are as follows: Isolation and establishment of CSCs using FACS based on cell surface markers and high ALDH1 activity. Identification and characterization of lung cancer stem cells that acquire features of CSC upon exposure to ionizing radiation. Evaluation of the fibulin-3 effects on the stem traits and signaling pathways required for the generation and maintenance of CSCs. In vivo validation of fivulin-3 for tumor prognosis and therapeutic efficacy against lung cancer using animal model.

  15. Tocotrienols are good adjuvants for developing cancer vaccines

    International Nuclear Information System (INIS)

    Dendritic cells (DCs) have the potential for cancer immunotherapy due to their ability to process and present antigens to T-cells and also in stimulating immune responses. However, DC-based vaccines have only exhibited minimal effectiveness against established tumours in mice and humans. The use of appropriate adjuvant enhances the efficacy of DC based cancer vaccines in treating tumours. In this study we have used tocotrienol-rich fraction (TRF), a non-toxic natural compound, as an adjuvant to enhance the effectiveness of DC vaccines in treating mouse mammary cancers. In the mouse model, six-week-old female BALB/c mice were injected subcutaneously with DC and supplemented with oral TRF daily (DC+TRF) and DC pulsed with tumour lysate from 4T1 cells (DC+TL). Experimental mice were also injected with DC pulsed with tumour lysate and supplemented daily with oral TRF (DC+TL+TRF) while two groups of animal which were supplemented daily with carrier oil (control) and with TRF (TRF). After three times vaccination, mice were inoculated with 4T1 cells in the mammary breast pad to induce tumour. Our study showed that TRF in combination with DC pulsed with tumour lysate (DC+TL+TRF) injected subcutaneously significantly inhibited the growth of 4T1 mammary tumour cells as compared to control group. Analysis of cytokines production from murine splenocytes showed significant increased productions of IFN-γ and IL-12 in experimental mice (DC+TL+TRF) compared to control, mice injected with DC without TRF, mice injected with DC pulsed with tumour lysate and mice supplemented with TRF alone. Higher numbers of cytotoxic T cells (CD8) and natural killer cells (NK) were observed in the peripheral blood of TRF adjuvanted DC pulsed tumour lysate mice. Our study show that TRF has the potential to be an adjuvant to augment DC based immunotherapy

  16. Tocotrienols are good adjuvants for developing cancer vaccines

    Directory of Open Access Journals (Sweden)

    Radhakrishnan Ammu

    2010-01-01

    Full Text Available Abstract Background Dendritic cells (DCs have the potential for cancer immunotherapy due to their ability to process and present antigens to T-cells and also in stimulating immune responses. However, DC-based vaccines have only exhibited minimal effectiveness against established tumours in mice and humans. The use of appropriate adjuvant enhances the efficacy of DC based cancer vaccines in treating tumours. Methods In this study we have used tocotrienol-rich fraction (TRF, a non-toxic natural compound, as an adjuvant to enhance the effectiveness of DC vaccines in treating mouse mammary cancers. In the mouse model, six-week-old female BALB/c mice were injected subcutaneously with DC and supplemented with oral TRF daily (DC+TRF and DC pulsed with tumour lysate from 4T1 cells (DC+TL. Experimental mice were also injected with DC pulsed with tumour lysate and supplemented daily with oral TRF (DC+TL+TRF while two groups of animal which were supplemented daily with carrier oil (control and with TRF (TRF. After three times vaccination, mice were inoculated with 4T1 cells in the mammary breast pad to induce tumour. Results Our study showed that TRF in combination with DC pulsed with tumour lysate (DC+TL+TRF injected subcutaneously significantly inhibited the growth of 4T1 mammary tumour cells as compared to control group. Analysis of cytokines production from murine splenocytes showed significant increased productions of IFN-γ and IL-12 in experimental mice (DC+TL+TRF compared to control, mice injected with DC without TRF, mice injected with DC pulsed with tumour lysate and mice supplemented with TRF alone. Higher numbers of cytotoxic T cells (CD8 and natural killer cells (NK were observed in the peripheral blood of TRF adjuvanted DC pulsed tumour lysate mice. Conclusion Our study show that TRF has the potential to be an adjuvant to augment DC based immunotherapy.

  17. Process and results of the development of an ICNP® Catalogue for Cancer Pain

    Directory of Open Access Journals (Sweden)

    Marisaulina Wanderley Abrantes de Carvalho

    2013-10-01

    Full Text Available This was a methodological study conducted to describe the process and results of the development of an International Classification for Nursing Practice (ICNP® Catalogue for Cancer Pain. According to the International Council of Nurses (ICN, this catalogue contains a subset of nursing diagnoses, outcomes, and interventions to document the implementation of the nursing process in cancer patients. This catalogue was developed in several steps according to the guidelines recommended by the ICN. As a result, 68 statements on nursing diagnoses/outcomes were obtained, which were classified according to the theoretical model for nursing care related to cancer pain into physical (28, psychological (29, and sociocultural and spiritual (11 aspects. A total of 116 corresponding nursing interventions were obtained. The proposed ICNP® Catalogue for Cancer Pain aims to provide safe and systematic orientation to nurses who work in this field, thus improving the quality of patient care and facilitating the performance of the nursing process.

  18. PREVENT Cancer Preclinical Drug Development Program (PREVENT) | Division of Cancer Prevention

    Science.gov (United States)

    The PREVENT program provides a structure for the introduction of new agents, drugs and vaccines to inhibit, retard or reverse the cancer process. The program was designed to optimize translational opportunities from discovery to the clinic, and provide a mechanism to identify and study efficacy and pharmacodynamics biomarkers that will help in phase II trials to evaluate drug effects.  | Research pipeline for new prevention interventions and biomarkers headed toward clinical trials.

  19. Radiopharmaceuticals based on 177LU for radionuclide therapy. Development of labeling procedures and Quality control methods

    International Nuclear Information System (INIS)

    The cancer in Cuba constitutes a fundamental problem of health and it occupies the second place as cause of death. It is known that the use of labeled biomolecules (like monoclonal antibodies-mAb- and peptides) with radioisotopes has become a viable and promissory alternative for the cancer. The monoclonal antibodies production in Cuba for different uses enjoys national and international prestige. Some years ago, the Center of Molecular Immunology (CIM) and the Isotope Center (CENTIS) joined efforts to develop the applications of the Cuban monoclonal antibodies. Different clinical trials have been carried out to explore the possibilities of the radioimmunotherapy in humans using monoclonal antibodies. We have been developed different radiopharmaceuticals based on monoclonal antibodies labeled with β emitters (131I, 188Re and 90Y). Because of 177Lu is one of the isotopes emerging as a clear choice for therapy, we expect that we can develop a 177Lu radiopharmaceutical based on h-R3 monoclonal antibody (Nimotuzumab). DOTA-conjugated monoclonal antibody could be radiolabelled with 177Lu with high yields, however our main focus will be to further optimize radiolabelling conditions to avoid side reactions. Labeling yields using different DOTA derivatives (DOTA-NHS, DOTA-SCN) were higher than 90%. Quality control evaluation was performed by HPLC and ITLC-SG. . (Author)

  20. Development of new therapeutic methods of lung cancer through team approach study

    Energy Technology Data Exchange (ETDEWEB)

    Park, Jong Ho; Zo, Jae Ill; Baek, Hee Jong; Jung, Jin Haeng; Lee, Jae Cheol; Ryoo, Baek Yeol; Kim, Mi Sook; Choi, Du Hwan; Park, Sun Young; Lee, Hae Young

    2000-12-01

    The aims of this study were to make the lung cancer clinics in Korea Cancer Center Hospital, and to establish new therapeutic methods of lung cancer for increasing the cure rate and survival rate of patients. Also another purpose of this study was to establish a common treatment method in our hospital. All patients who were operated in Korea Cancer Center Hospital from 1987 due to lung cancer were followed up and evaluated. And we have been studied the effect of postoperative adjuvant therapy in stage I, II, IIIA non-small cell lung cancer patients from 1989 with the phase three study form. Follow-up examinations were scheduled in these patients and interim analysis was made. Also we have been studied the effect of chemo-therapeutic agents in small cell lung cancer patients from 1997 with the phase two study form. We evaluated the results of this study. Some important results of this study were as follows. 1. The new therapeutic method (surgery + MVP chemotherapy) was superior to the standard therapeutic one in stage I Non-small cell lung cancer patients. So, we have to change the standard method of treatment in stage I NSCLC. 2. Also, this new therapeutic method made a good result in stage II NSCLC patients. And this result was reported in The Annals of Thoracic Surgery. 3. However, this new therapeutic method was not superior to the standard treatment method (surgery only) in stage IIIA NSCLC patients. So, we must develop new chemo-therapeutic agents in the future for advanced NSCLC patients. 4. In the results of the randomized phase II studies about small cell lung cancer, there was no difference in survival between Etoposide + Carboplatin + Ifosfamide + Cisplatin group and Etoposide + Carboplatin + Ifosfamide + Cisplatin + Tamoxifen group in both the limited and extended types of small cell lung cancer patients.

  1. Development of new therapeutic methods of lung cancer through team approach study

    International Nuclear Information System (INIS)

    The aims of this study were to make the lung cancer clinics in Korea Cancer Center Hospital, and to establish new therapeutic methods of lung cancer for increasing the cure rate and survival rate of patients. Also another purpose of this study was to establish a common treatment method in our hospital. All patients who were operated in Korea Cancer Center Hospital from 1987 due to lung cancer were followed up and evaluated. And we have been studied the effect of postoperative adjuvant therapy in stage I, II, IIIA non-small cell lung cancer patients from 1989 with the phase three study form. Follow-up examinations were scheduled in these patients and interim analysis was made. Also we have been studied the effect of chemo-therapeutic agents in small cell lung cancer patients from 1997 with the phase two study form. We evaluated the results of this study. Some important results of this study were as follows. 1. The new therapeutic method (surgery + MVP chemotherapy) was superior to the standard therapeutic one in stage I Non-small cell lung cancer patients. So, we have to change the standard method of treatment in stage I NSCLC. 2. Also, this new therapeutic method made a good result in stage II NSCLC patients. And this result was reported in The Annals of Thoracic Surgery. 3. However, this new therapeutic method was not superior to the standard treatment method (surgery only) in stage IIIA NSCLC patients. So, we must develop new chemo-therapeutic agents in the future for advanced NSCLC patients. 4. In the results of the randomized phase II studies about small cell lung cancer, there was no difference in survival between Etoposide + Carboplatin + Ifosfamide + Cisplatin group and Etoposide + Carboplatin + Ifosfamide + Cisplatin + Tamoxifen group in both the limited and extended types of small cell lung cancer patients

  2. Clinical endpoints for developing pharmaceuticals to manage patients with sporadic or genetic risk of colorectal cancer

    OpenAIRE

    Rial, Nathaniel S; Zell, Jason A.; Cohen, Alfred M.; Gerner, Eugene W.

    2012-01-01

    To reduce the morbidity and mortality from colorectal cancer, current clinical practice focuses on screening for early detection and polypectomy as a form of secondary prevention, complemented with surgical interventions when appropriate. No pharmaceutical agent is currently approved for use in clinical practice for the management of patients with risk of colorectal cancer. This article will review earlier attempts to develop pharmaceuticals for use in managing patients with sporadic or genet...

  3. Myeloid-derived suppressor cells in the development of lung cancer

    OpenAIRE

    Ortiz, Myrna L.; Lu, Lily; Ramachandran, Indu; Gabrilovich, Dmitry I.

    2013-01-01

    Myeloid-derived suppressor cells (MDSC) are widely implicated in immune suppression associated with tumor progression and chronic inflammation. However, very little is known about their possible role in tumor development. Here, we evaluated the role of MDSC in two experimental models of lung cancer: inflammation-associated lung cancer caused by chemical carcinogen urethane in combination with exposure to cigarette smoke (CS); and transgenic CC10Tg model not associated with inflammation. Expos...

  4. 2015 Guidance on cancer immunotherapy development in early‐phase clinical studies

    OpenAIRE

    ,; Arato, Teruyo; Daimon, Takashi; Heike, Yuji; Ishii, Ken; Itho, Kyogo; KAGEYAMA, SHINICHI; Kawakami, Yutaka; Nakayama, Eiichi; Ozawa, Keiya; Sato, Noriyuki; Shiku, Hiroshi; Takeuchi, Masahiro; Tani, Kenzaburo; Tamada, Koji

    2015-01-01

    The development of cancer immunotherapies is progressing rapidly with a variety of technological approaches. They consist of “cancer vaccines”, which are based on the idea of vaccination, “effector cell therapy”, classified as passive immunotherapy, and “inhibition of immunosuppression”, which intends to break immunological tolerance to autoantigens or immunosuppressive environments characterizing antitumor immune responses. Recent reports showing clinical evidence of efficacy of immune check...

  5. Breast cancer surface receptors predict risk for developing brain metastasis and subsequent prognosis

    OpenAIRE

    Grewal, Jai; Kesari, Santosh

    2008-01-01

    Determining the status of breast cancer surface receptors (estrogen receptor, progesterone receptor, HER2/neu) has become routine in the care of patients with this disease and has proven to be helpful in guiding treatment. For this reason, breast cancer has become a model for molecularly guided therapy in solid tumors. Emerging data support that these receptors are associated with risk for developing brain metastases. Additionally, once brain metastases have occurred these receptors may also ...

  6. Potential of Drug Interactions among Hospitalized Cancer Patients in a Developing Country

    OpenAIRE

    Tavakoli-Ardakani, Maria; Kazemian, Kaveh; Salamzadeh, Jamshid; Mehdizadeh, Mahshid

    2013-01-01

    Cancer patients are more susceptible to adverse drug-drug interactions (DDIs) due to receiving multiple medications especially chemotherapy medications, hormonal agents and supportive care drugs. The aim of this study is to describe the prevalence of potential DDIs and to identify risk factors for these potential interactions in hospitalized cancer patients in a developing country. A cross-sectional study conducted by reviewing charts of 224 consecutive in hospitalized patients in hematology-...

  7. Novel compounds in the treatment of lung cancer: current and developing therapeutic agents

    OpenAIRE

    Bao, Rudi; Chan, PokMan

    2011-01-01

    Lung cancer is the leading cause of cancer-related death in the United States. Though incremental advances have been made in the treatment of this devastating disease during the past decade, new therapies are urgently needed. Traditional cytotoxic agents have been combined with other modalities with improved survival for early-stage patients. Newer cytotoxic agents targeting the same or different mechanisms have been developed at different stages. Optimization of various chemotherapy regimens...

  8. 131I-Tositumomab Myeloablative Radioimmunotherapy for Non-Hodgkin's Lymphoma: Radiation Dose to the Testes

    Energy Technology Data Exchange (ETDEWEB)

    Hattori, Naoya; Gopal, Ajay K.; Shields, Andrew T.; Fisher, Darrell R.; Gooley, Ted; Pagel, John M.; Press, Oliver W.; Rajendran, Joseph G.

    2012-12-01

    To investigate radiation dose to testes delivered by radiolabeled anti-CD20 antibody and its effects on male sex hormone levels. METHODS: We evaluated dosimetry results for 67 male patients (54 ± 11 years old) with non-Hodgkin lymphoma who underwent myeloablative radioimmunotherapy (RIT) using 131I-tositumomab. In a subset of patients, male sex hormones were measured before and one year after the therapy. RESULTS: Absorbed dose to testes showed greater variability (range = 4.4 to 70.2 Gy) than did dose to lungs (9.5 to 28.4 Gy, p < 0.0001) or liver (6.5 to 27.2 Gy, p < 0.0001). Absorbed dose to the testes per 131I administered (1.18 ± 0.59 mGy/MBq) was not significantly different from that to the liver (1.03 ± 0.29 mGy/MBq, p = 0.08), or to the lungs (1.19 ± 0.50 mGy/MBq, p = 0.889). Pre-therapy levels of total testosterone were below the lower limit of the reference range, and post-therapy evaluation demonstrated further reduction (4.6 ± 1.8 nmol/L (pre-RIT) vs. 3.8 ± 2.9 nmol/L (post-RIT), p < 0.05). Patients receiving higher radiation doses to the testes (≥ 25 Gy) showed a greater reduction (4.7 ± 1.6 nmol/L (pre RIT) vs. 3.3 ± 2.7 nmol/L (post-RIT), p < 0.05) than did patients receiving lower doses (< 25 Gy), who showed no significant change in total testosterone levels. CONCLUSION: The testicular radiation absorbed dose varied highly among individual patients. Patients receiving higher doses to testes were more likely to show post-RIT suppression of testosterone levels. Key Words: 131I-tositumomab, follicular lymphoma, radioimmunotherapy, radiation dosimetry, male sex hormones.  

  9. Targeted alpha therapy in vivo: direct evidence for single cancer cell kill using {sup 149}Tb-rituximab

    Energy Technology Data Exchange (ETDEWEB)

    Beyer, G.J.; Soloviev, D.; Buchegger, F. [Division of Nuclear Medicine, University Hospital of Geneva, 24 Rue Micheli du Crest, 1211, Geneva 14 (Switzerland); Miederer, M. [Department of Molecular Pharmacology and Chemistry, Memorial Sloan-Kettering Cancer Center, New York (United States); Vranjes-Duric, S. [Laboratory of Radioisotopes, Vinca Institute of Nuclear Sciences, Belgrade (Czechoslovakia); Comor, J.J. [Laboratory of Physics, Vinca Institute of Nuclear Sciences, Belgrade (Czechoslovakia); Kuenzi, G.; Hartley, O. [Department of Medical Biochemistry, University Medical Center, Geneva (Switzerland); Senekowitsch-Schmidtke, R. [Clinic of Nuclear Medicine, Technical University of Munich, Munich (Germany)

    2004-04-01

    This study demonstrates high-efficiency sterilisation of single cancer cells in a SCID mouse model of leukaemia using rituximab, a monoclonal antibody that targets CD20, labelled with terbium-149, an alpha-emitting radionuclide. Radio-immunotherapy with 5.5 MBq labelled antibody conjugate (1.11 GBq/mg) 2 days after an intravenous graft of 5.10{sup 6} Daudi cells resulted in tumour-free survival for >120 days in 89% of treated animals. In contrast, all control mice (no treatment or treated with 5 or 300 {mu}g unlabelled rituximab) developed lymphoma disease. At the end of the study period, 28.4%{+-}4% of the long-lived daughter activity remained in the body, of which 91.1% was located in bone tissue and 6.3% in the liver. A relatively high daughter radioactivity concentration was found in the spleen (12%{+-}2%/g), suggesting that the killed cancer cells are mainly eliminated through the spleen. This promising preliminary in vivo study suggests that targeted alpha therapy with {sup 149}Tb is worthy of consideration as a new-generation radio-immunotherapeutic approach. (orig.)

  10. Targeting autophagy in cancer management – strategies and developments

    International Nuclear Information System (INIS)

    Autophagy is a highly regulated catabolic process involving lysosomal degradation of intracellular components, damaged organelles, misfolded proteins, and toxic aggregates, reducing oxidative stress and protecting cells from damage. The process is also induced in response to various conditions, including nutrient deprivation, metabolic stress, hypoxia, anticancer therapeutics, and radiation therapy to adapt cellular conditions for survival. Autophagy can function as a tumor suppressor mechanism in normal cells and dysregulation of this process (ie, monoallelic Beclin-1 deletion) may lead to malignant transformation and carcinogenesis. In tumors, autophagy is thought to promote tumor growth and progression by helping cells to adapt and survive in metabolically-challenged and harsh tumor microenvironments (ie, hypoxia and acidity). Recent in vitro and in vivo studies in preclinical models suggested that modulation of autophagy can be used as a therapeutic modality to enhance the efficacy of conventional therapies, including chemo and radiation therapy. Currently, more than 30 clinical trials are investigating the effects of autophagy inhibition in combination with cytotoxic chemotherapies and targeted agents in various cancers. In this review, we will discuss the role, molecular mechanism, and regulation of autophagy, while targeting this process as a novel therapeutic modality, in various cancers

  11. The effect of folic acid on the development of stomach and other gastrointestinal cancers

    Institute of Scientific and Technical Information of China (English)

    2003-01-01

    Objective To evaluate the roles of folic acid and β-carotene in the chemoprevention of gastric and other gastrointestinal (GI) cancers. Results A total of 7 new cases of gastrointestinal cancers were diagnosed with 3 stomach, 1 colon and 1 esophageal cancers occurring in the placebo group; 1 stomach cancer in both of the N-βC and S-βC groups, and no cancer occurring in FA group. In terms of GI cancers, there was a significant reduction in the FA group, compared with the placebo group (P=0.04). A similar trend was observed in both N-βC and S-βC groups (P=0.07-0.08). Taken together, the three intervention groups displayed a highly significant decrease in occurrence (P=0.004, vs placebo), and a lower risk for GI cancers (OR=0.12; 95% confidence interval, 0.03-0.51). For development of gastric cancer, any one of the three active-treated groups did not reach statistically significant reduction. The FA group showed obvious improvement of the gastric mucosal lesions with more patients displaying lesions reversed or stable atrophy and inflammation (P=0.04), reversed intestinal metaplasia (P=0.06) at the end of follow-up, and reversed displasia (P=0.017) at 12 months. Two cases of false jaundice were found in β-carotene groups with no influence on administration, and no side-effects were reported in FA group. Conclusions This trial revealed the interventional effect of folic acid on the development of GI cancers, a similar effect of β-carotene was also detected. Also, folic acid may be of use to treat atrophic gastritis by preventing or reversing the precancerous lesions.

  12. 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

  13. The pharmaceuticalization of sexual risk: vaccine development and the new politics of cancer prevention.

    Science.gov (United States)

    Mamo, Laura; Epstein, Steven

    2014-01-01

    Vaccine development is a core component of pharmaceutical industry activity and a key site for studying pharmaceuticalization processes. In recent decades, two so-called cancer vaccines have entered the U.S. medical marketplace: a vaccine targeting hepatitis B virus (HBV) to prevent liver cancers and a vaccine targeting human papillomavirus (HPV) to prevent cervical and other cancers. These viruses are two of six sexually transmissible infectious agents (STIs) that are causally linked to the development of cancers; collectively they reference an expanding approach to apprehending cancer that focuses attention simultaneously "inward" toward biomolecular processes and "outward" toward risk behaviors, sexual practices, and lifestyles. This paper juxtaposes the cases of HBV and HPV and their vaccine trajectories to analyze how vaccines, like pharmaceuticals more generally, are emblematic of contemporary pharmaceuticalization processes. We argue that individualized risk, in this case sexual risk, is produced and treated by scientific claims of links between STIs and cancers and through pharmaceutical company and biomedical practices. Simultaneous processes of sexualization and pharmaceuticalization mark these cases. Our comparison demonstrates that these processes are not uniform, and that the production of risks, subjects, and bodies depends not only on the specificities of vaccine development but also on the broader political and cultural frames within which sexuality is understood. PMID:24560236

  14. 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

  15. 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

    International Nuclear Information System (INIS)

    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 89Zr or 124I, were prepared. 89Zr 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 124I-J591 than for 89Zr-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 89Zr or 124I 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-drug conjugates. Further exploration using the

  16. 124I-L19-SIP for immuno-PET imaging of tumour vasculature and guidance of 131I-L19-SIP radioimmunotherapy

    International Nuclear Information System (INIS)

    The human monoclonal antibody (MAb) fragment L19-SIP is directed against extra domain B (ED-B) of fibronectin, a marker of tumour angiogenesis. A clinical radioimmunotherapy (RIT) trial with 131I-L19-SIP was recently started. In the present study, after GMP production of 124I and efficient production of 124I-L19-SIP, we aimed to demonstrate the suitability of 124I-L19-SIP immuno-PET for imaging of angiogenesis at early-stage tumour development and as a scouting procedure prior to clinical 131I-L19-SIP RIT. 124I was produced in a GMP compliant way via 124Te(p,n)124I reaction and using a TERIMO trademark module for radioiodine separation. L19-SIP was radioiodinated by using a modified version of the IODO-GEN method. The biodistribution of coinjected 124I- and 131I-L19-SIP was compared in FaDu xenograft-bearing nude mice, while 124I PET images were obtained from mice with tumours of 3. 124I was produced highly pure with an average yield of 15.4 ± 0.5 MBq/μAh, while separation yield was ∝90% efficient with 2. Overall labelling efficiency, radiochemical purity and immunoreactive fraction were for 124I-L19-SIP: ∝80, 99.9 and >90%, respectively. Tumour uptake was 7.3±2.1, 10.8±1.5, 7.8±1.4, 5.3±0.6 and 3.1±0.4%ID/g at 3, 6, 24, 48 and 72 h p.i., resulting in increased tumour to blood ratios ranging from 6.0 at 24 h to 45.9 at 72 h p.i. Fully concordant labelling and biodistribution results were obtained with 124I- and 131I-L19-SIP. Immuno-PET with 124I-L19-SIP using a high-resolution research tomograph PET scanner revealed clear delineation of the tumours as small as 50 mm3 and no adverse uptake in other organs. 124I-MAb conjugates for clinical immuno-PET can be efficiently produced. Immuno-PET with 124I-L19-SIP appeared qualified for sensitive imaging of tumour neovasculature and for predicting 131I-L19-SIP biodistribution. (orig.)

  17. α-Imaging Confirmed Efficient Targeting of CD₄₅-Positive Cells After ²¹¹At-Radioimmunotherapy for Hematopoietic Cell Transplantation

    Energy Technology Data Exchange (ETDEWEB)

    Frost, Sophia; Miller, Brian W.; Back, Tom; Santos, E. B.; Hamlin, Donald K.; Knoblaugh, E.; Frayo, Shani; Kenoyer, Aimee L.; Storb, Rainer; Press, O. W.; Wilbur, D. Scott; Pagel, John M.; Sandmaier, B. M.

    2015-09-03

    Alpha-radioimmunotherapy (α-RIT) targeting CD45 may substitute for total body irradiation in hematopoietic cell transplantation (HCT) preparative regimens for lymphoma. Our goal was to optimize the anti-CD45 monoclonal antibody (MAb; CA12.10C12) protein dose for astatine-²¹¹(²¹¹At)-RIT, extending the analysis to include intra-organ ²¹¹At activity distribution and α-imaging-based small-scale dosimetry, along with imunohistochemical staining. Methods: Eight normal dogs were injected with either 0.75 (n=5) or 1.00 mg/kg (n=3) of ²¹¹At-B10-CA12.10C12 (11.5–27.6 MBq/kg). Two were euthanized and necropsied 19–22 hours postinjection (p.i.), and six received autologous HCT three days after ²¹¹At-RIT, following lymph node and bone marrow biopsies at 2–4 and/or 19 hours p.i. Blood was sampled to study toxicity and clearance; CD45 targeting was evaluated by flow cytometry. ²¹¹At localization and small scale dosimetry were assessed using two α-imaging : α-camera and iQID. Results: Uptake of ²¹¹At was highest in spleen (0.31–0.61 %IA/g), lymph nodes (0.02–0.16 %IA/g), liver (0.11–0.12 %IA/g), and marrow (0.06–0.08 %IA/g). Lymphocytes in blood and marrow were efficiently targeted using either MAb dose. Lymph nodes remained unsaturated, but displayed targeted ²¹¹At localization in T lymphocyte-rich areas. Absorbed doses to blood, marrow, and lymph nodes were estimated at 3.9, 3.0, and 4.2 Gy/210 MBq, respectively. All transplanted dogs experienced transient hepatic toxicity. Liver enzyme levels were temporarily elevated in 5 of 6 dogs; 1 treated with 1.00 mg MAb/kg developed ascites and was euthanized 136 days after HCT. Conclusion: ²¹¹At-anti-CD45 RIT with 0.75 mg MAb/kg efficiently targeted blood and marrow without severe toxicity. Dosimetry calculations and observed radiation-induced effects indicated that sufficient ²¹¹At-B10-CA12.10C12 localization was achieved for efficient conditioning for HCT.

  18. Cervical cancer vaccine: Exploring new opportunities and challenges for developing countries

    Directory of Open Access Journals (Sweden)

    Ananya Ray Laskar

    2011-01-01

    Full Text Available Cervical cancer is the second most common cancer in women worldwide, and the burden of the disease is disproportionately high in the developing world (>80%. With the advent of two new vaccines, "Gardasil" developed by Merck & Co. New Jersey, USA and "Cervarix" developed by GlaxoSmithKline (GSK in Philadelphia, USA, the future holds newer promises for prevention and control of the disease. However, various regulatory and policy changes also may be required to be undertaken and the various new challenges need to be addressed.

  19. Awareness that early cancer lump is painless could decrease breast cancer mortality in developing countries

    OpenAIRE

    Garg, Pankaj

    2016-01-01

    There are several factors which contribute to patients’ reporting late to healthcare facility even after detecting the breast lump (patient delay). Amongst these, one of the important factors in low- and middle-income countries is lack of awareness that early cancer lump is painless (ECLIPs). Pain is often taken as a danger sign and absence of pain is often not taken seriously. The studies have shown that up to 98% of women in low-income countries are unaware that a painless lump could be a w...

  20. Development of radioactively labeled cancer seeking biomolecules for targeted radiotherapy

    International Nuclear Information System (INIS)

    As meanwhile demonstrated by different groups a variety of human tumours express a large number of peptide receptors with a high affinity for VIP and SST. Radiolabeled synthetic analogs of this peptide hormones have been shown to be effective in diagnosis of SST receptor positive tumours and metastases. This fact seems to be a promising starting point for the therapeutic use of this cancer seeking tracer molecules for targeted radiotherapy. In this project we have focused our work on the preparation of DOTA-Lanreotide (Mauritius), a novel SST analog, which shows a high affinity to several SST receptors expressed by neuroendocrine tumours. This radiolabeled tracer actually is under evaluation by a European multicenter study for its diagnostic and therapeutic capacity

  1. Differential expression of CHL1 gene during development of major human cancers.

    Directory of Open Access Journals (Sweden)

    Vera N Senchenko

    Full Text Available BACKGROUND: CHL1 gene (also known as CALL on 3p26.3 encodes a one-pass trans-membrane cell adhesion molecule (CAM. Previously CAMs of this type, including L1, were shown to be involved in cancer growth and metastasis. METHODOLOGY/PRINCIPAL FINDINGS: We used Clontech Cancer Profiling Arrays (19 different types of cancers, 395 samples to analyze expression of the CHL1 gene. The results were further validated by RT-qPCR for breast, renal and lung cancer. Cancer Profiling Arrays revealed differential expression of the gene: down-regulation/silencing in a majority of primary tumors and up-regulation associated with invasive/metastatic growth. Frequent down-regulation (>40% of cases was detected in 11 types of cancer (breast, kidney, rectum, colon, thyroid, stomach, skin, small intestine, bladder, vulva and pancreatic cancer and frequent up-regulation (>40% of cases--in 5 types (lung, ovary, uterus, liver and trachea of cancer. Using real-time quantitative PCR (RT-qPCR we found that CHL1 expression was decreased in 61% of breast, 60% of lung, 87% of clear cell and 89% papillary renal cancer specimens (P<0.03 for all the cases. There was a higher frequency of CHL1 mRNA decrease in lung squamous cell carcinoma compared to adenocarcinoma (81% vs. 38%, P = 0.02 without association with tumor progression. CONCLUSIONS/SIGNIFICANCE: Our results suggested that CHL1 is involved in the development of different human cancers. Initially, during the primary tumor growth CHL1 could act as a putative tumor suppressor and is silenced to facilitate in situ tumor growth for 11 cancer types. We also suggested that re-expression of the gene on the edge of tumor mass might promote local invasive growth and enable further metastatic spread in ovary, colon and breast cancer. Our data also supported the role of CHL1 as a potentially novel specific biomarker in the early pathogenesis of two major histological types of renal cancer.

  2. Throat or larynx cancer

    Science.gov (United States)

    Vocal cord cancer; Throat cancer; Laryngeal cancer; Cancer of the glottis; Cancer of oropharynx or hypopharynx ... use tobacco are at risk of developing throat cancer. Drinking too much alcohol over a long time ...

  3. Association between XPG gene polymorphisms and development of gastric cancer risk in a Chinese population.

    Science.gov (United States)

    Feng, Y B; Fan, D Q; Yu, J; Bie, Y K

    2016-01-01

    We conducted a case-control study to investigate the role of three common single nucleotide polymorphisms (SNPs) in the xeroderma pigmentosum complementation group G (XPG) gene (rs2094258, rs751402 and rs17655) in the development of gastric cancer in a Chinese population. Between January 2012 and December 2014, samples from a total of 177 patients with gastric cancer and 237 control subjects were collected from the Ankang City Central Hospital. XPG rs2094258, rs751402 and rs17655 polymorphisms were genotyped using polymerase chain reaction-restriction fragment length polymorphism. Using logistic regression analysis, we found that the CC genotype of rs17655 was associated with an elevated risk of gastric cancer, and the adjusted odds ratio (OR) and 95% confidence intervals (95%CI) were 1.91 and 1.07-3.41, respectively. Moreover, individuals carrying the GC + CC genotype of rs17655 had an increased susceptibility to gastric cancer (OR = 1.61, 95%CI = 1.03-2.54). However, we did not observe a significant association between XPG rs2094258 and rs751402 polymorphisms and development of gastric cancer. In conclusion, our study suggests that the rs17655 polymorphism in XPG is associated with an increased risk of gastric cancer. The results of our findings should be further validated by further large sample size studies. PMID:27323165

  4. 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.

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

    International Nuclear Information System (INIS)

    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.

  6. The Importance of Autophagy Regulation in Breast Cancer Development and Treatment

    Directory of Open Access Journals (Sweden)

    Joanna Magdalena Zarzynska

    2014-01-01

    Full Text Available Breast cancer (BC is a potentially life-threatening malignant tumor that still causes high mortality among women. One of the mechanisms through which cancer development could be controlled is autophagy. This process exerts different effects during the stages of cancer initiation and progression due to the occurring superimposition of signaling pathways of autophagy and carcinogenesis. Chronic inhibition of autophagy or autophagy deficiency promotes cancer, due to instability of the genome and defective cell growth and as a result of cell stress. However, increased induction of autophagy can become a mechanism which allows tumor cells to survive the conditions of hypoxia, acidosis, or chemotherapy. Therefore, in the development of cancer, autophagy is regarded as a double-edged sword. Determination of the molecular mechanisms underlying autophagy regulation and its role in tumorigenesis is an essential component of modern anticancer strategies. Results of scientific studies show that inhibition of autophagy may enhance the effectiveness of currently used anticancer drugs and other therapies (like radiotherapy. However, in some cases, the promotion of autophagy can induce death and, hence, elimination of the cancer cells and reduction of tumor size. This review summarizes the current knowledge on autophagy regulation in BC and up-to-date anticancer strategies correlated with autophagy.

  7. Exploiting Nanotechnology for the Development of MicroRNA-Based Cancer Therapeutics.

    Science.gov (United States)

    Tyagi, Nikhil; Arora, Sumit; Deshmukh, Sachin K; Singh, Seema; Marimuthu, Saravanakumar; Singh, Ajay P

    2016-01-01

    MicroRNAs (miRNAs/miRs) represent a novel class of small non-coding RNAs that post-transcriptionally regulate gene expression by base pairing with complementary sequences in the 3' untranslated region (UTR) of target mRNAs. Functional studies suggest that miRNAs control almost every biological process, and their aberrant expression leads to a disease state, such as cancer. Differential expression of miRNAs in cancerous versus normal cells have generated enormous interest for the development of miRNA-based cancer cell-targeted therapeutics. Depending on the miRNA function and expression in cancer, two types of miRNA-based therapeutic strategies can be utilized that either restore or inhibit miRNA function through exogenous delivery of miRNAs mimics or inhibitors (anti-miRs). However, hydrophilic nature of miRNA mimics/anti-miRs, sensitivity to nuclease degradation in serum, poor penetration and reduced uptake by the tumor cells are chief hurdles in accomplishing their efficient in vivo delivery. To overcome these barriers, several nanotechnology-based systems are being developed and tested for delivery efficacy. This review summarizes the importance of miRNAs-based therapeutics in cancer, associated translational challenges and novel nanotechnology-assisted delivery systems that hold potential for next-generation miRNA-based cancer therapeutics. PMID:27301170

  8. Validation of prospective whole-body bone marrow dosimetry by SPECT/CT multimodality imaging in {sup 131}I-anti-CD20 rituximab radioimmunotherapy of non-Hodgkin's lymphoma

    Energy Technology Data Exchange (ETDEWEB)

    Boucek, Jan A. [Fremantle Hospital, Department of Nuclear Medicine, Fremantle (Australia); Turner, J. Harvey [Fremantle Hospital, Department of Nuclear Medicine, Fremantle (Australia); University of Western Australia, School of Medicine and Pharmacology (Australia)

    2005-04-01

    Radioimmunotherapy (RIT) for relapsed non-Hodgkin's lymphoma is emerging as a promising treatment strategy. Myelosuppression is the dose-limiting toxicity and may be particularly problematic in patients heavily pretreated with chemotherapy. Reliable dosimetry is likely to minimise toxicity and improve treatment efficacy, and the aim of this study was to elucidate the complex problems of dosimetry of RIT by using an integrated SPECT/CT system. As a part of a clinical trial of {sup 131}I-anti-CD20 rituximab RIT of non-Hodgkin's lymphoma, we employed a patient-specific prospective dosimetry method utilising the whole-body effective half-life of antibody and the patient's ideal weight to calculate the administered activity for RIT corresponding to a prescribed radiation absorbed dose of 0.75 Gy to the whole body. A novel technique of quantitation of bone marrow uptake with hybrid SPECT/CT imaging was developed to validate this methodology by using post-RIT extended imaging and data collection. A strong, statistically significant correlation (p=0.001) between whole-body effective half-life of antibody and effective marrow half-life was demonstrated. Furthermore, it was found that bone marrow activity concentration was proportional to administered activity per unit weight, height or body surface area (p<0.001). The results of this study show the proposed whole-body dosimetry method to be valid and clinically applicable for safe, effective RIT. (orig.)

  9. Genomics and premalignant breast lesions: clues to the development and progression of lobular breast cancer

    OpenAIRE

    Mastracci, Teresa L; Boulos, Fouad I; Andrulis, Irene L.; Lam, Wan L.

    2007-01-01

    Advances in genomic technology have improved our understanding of the genetic events that parallel breast cancer development. Because almost all mammary carcinomas develop in the terminal duct lobular units of the breast, understanding the events involved in mammary gland development make it possible to recognize those events that, when altered, contribute to breast neoplasia. In this review we focus on lobular carcinomas, discussing the pathology, development, and progression of premalignant...

  10. About the Chemopreventive Agent Development Research Group | Division of Cancer Prevention

    Science.gov (United States)

    The Chemopreventive Agent Development Research Group promotes and supports research on early chemopreventive agent development, from preclinical studies to phase I clinical trials. The group’s projects aim to identify and develop prevention agents with the potential to block, reverse, or delay the early stages of cancer. The overarching goal is to determine positive and negative predictive values of preclinical models for clinical development. |

  11. Dosimetric evaluation of copper-64 in copper-67-2IT-BAT-Lym-1 for radioimmunotherapy

    International Nuclear Information System (INIS)

    Copper 67 (67Cu) is an attractive radionuclide for radioimmunotherapy because of its favorable physical and biologic characteristics. Current supplies of 67Cu, however, contain as much as 60% of 64Cu at the time of delivery. Scatter photons from 64Cu enter the 67Cu energy window, affecting image resolution and counting accuracy. The radiation dose to tissue is also altered. A line source and a small vial source of 67Cu containing varying amounts of 64Cu were used to evaluate the impact of 64Cu on image resolution and activity quantitation, respectively. Identical pharmacokinetics for 67Cu and 64Cu was assumed, and the radiation dosimetry of 64Cu was assessed using quantitative imaging data for 67Cu because the amount of 64Cu could be calculated for any time after 67Cu production. MIRD formalism was used to estimate the therapeutic index, defined as the ratio of radiation dose to tumor divided by the radiation dose to bone marrow. The shorter physical half-life of 64Cu relative to that of 67Cu and slower uptake and longer retention of antibody by tumor than by marrow result in a lower therapeutic index for 64Cu. The 25% radioimpurity of 64Cu causes less than 10% deviation in activity quantitation and diminution in the therapeutic index. The change in therapeutic index is predictable over time and can be used to determine the optimal time for radiopharmaceutical administration. 34 refs., 4 figs., 2 tabs

  12. 131I-chTNT-mediated radioimmunotherapy for non-uptaking 131I pulmonary metastases from differentiated thyroid carcinoma

    International Nuclear Information System (INIS)

    In this paper, the safety and efficacy of 131I-labeled mouse/human chimeric monoclonal antibody (131I-chTNT)-mediated radioimmunotherapy are evaluated because the patients have non-uptaking 131I pulmonary metastases from differentiated thyroid carcinoma (DTC). The 16 patients were injected intravenously by 29.6±3.7 MBq·kg-1 using 131I-chTNT. The chest computer tomography was performed before treatment, as well as 28 and 70 days after treatment. Responses and safety were assessed during the treatment. The results show that the 131I-chTNT infusion was well tolerated with the 12.5% complete response, 18.8% partial response, 25.0% progressive disease, and the 43.8% stable disease, indicating that most treatment-related adverse effects are mild transient and reversible. The 131I-chTNT is promising for patients with non-uptaking the 131I pulmonary metastases from DTC. (authors)

  13. Use of PET volume determination by fuzzy logic in the follow up of lymphomas treated by radio-immunotherapy

    International Nuclear Information System (INIS)

    Purposes: the aim of this study was to assess if the evaluation of tumoral volumes by fuzzy logic was workable for clinical use. This study was performed with patients followed up for radio-immunotherapy of non-Hodgkin's lymphomas with a comparison of the respective contributions of this quantification and Standardized Uptake Value (S.U.V.). Materials and methods: thirty patients underwent 18F-FDG PET before treatment and then in an iterative way. The analysis of 217 lesions allowed to evaluate their volumes and S.U.V.. The evolution of these parameters of quantification was compared. Results: these two quantitative parameters did not statistically differ but there were important discrepancies in some examinations. The determination of volumes was sometimes limited by tumoral localization or junction of lesions. Conclusion: this study proved the feasibility of the determination of tumoral volumes by fuzzy method in clinical use. Quantification supplemented the subjective visual analysis, which in most cases was sufficient to appreciate the progression of the disease. This quantification, usually given by the value of the S.U.V., could be improved by the volume data either in a separated way, or combining intensity and volume (total lesion glycolysis). Further work is necessary to specify the predictive value of these parameters in this particular indication. (authors)

  14. RadioImmunotherapy for adenoid cystic carcinoma: a single-institution series of combined treatment with cetuximab

    Directory of Open Access Journals (Sweden)

    Weichert Wilko

    2010-11-01

    Full Text Available Abstract Background Local control in adjuvant/definitive RT of adenoid cystic carcinoma (ACC is largely dose-dependent. However, some clinical situations do not allow application of tumouricidal doses (i.e. re-irradiation hence radiation sensitization by exploitation of high endothelial growth factor receptor (EGFR-expression in ACC seems beneficial. This is a single-institution experience of combined radioimmunotherapy (RIT with the EGFR-inhibitor cetuximab. Methods Between 2006 and 2010, 9 pts received RIT for advanced/recurrent ACC, 5/9 pts as re-irradiation. Baseline characteristics as well as treatment parameters were retrieved to evaluate efficacy and toxicity of the combination regimen were evaluated. Control rates (local/distant and overall survival were calculated using Kaplan-Meier estimation. Results Median dose was 65 Gy, pts received a median of 6 cycles cetuximab. RIT was tolerated well with only one °III mucositis/dysphagia. Overall response/remission rates were high (77,8%; 2-year estimate of local control was 80% hence reaching local control levels comparable to high-dose RT. Progression-free survival (PFS at 2 years and median overall survival were only 62,5% and 22,2 mo respectively. Conclusion While local control and treatment response in RIT seems promising, PFS and overall survival are still hampered by distant failure. The potential benefit of RIT with cetuximab warrants exploration in a prospective controlled clinical trial.

  15. Gynaecological cancer

    OpenAIRE

    Jeffcoate, T. N. A.

    1999-01-01

    Gynaecological cancer encompasses a number of tumours with different epidemiology, pathology and treatment strategies. This article reviews the principal clinical advances and areas of development in cancer of the ovary, cervix, endometrium and vulva.


Keywords: ovarian cancer; cervical cancer; endometrial cancer; vulval cancer

  16. Cancer control in developing countries: using health data and health services research to measure and improve access, quality and efficiency

    OpenAIRE

    Kangolle Alfred CT; Hanna Timothy P

    2010-01-01

    Abstract Background Cancer is a rapidly increasing problem in developing countries. Access, quality and efficiency of cancer services in developing countries must be understood to advance effective cancer control programs. Health services research can provide insights into these areas. Discussion This article provides an overview of oncology health services in developing countries. We use selected examples from peer-reviewed literature in health services research and relevant publicly availab...

  17. Is quality of colorectal cancer care good enough? Core measures development and its application for comparing hospitals in Taiwan

    OpenAIRE

    Cheng Skye H; Kuo Raymond; Lai Mei-Shu; Chang Yun-Jau; Chung Kuo-Piao; Chen Li-Tzong; Tang Reiping; Liu Tsang-Wu; Shieh Ming-Jium

    2010-01-01

    Abstract Background Although performance measurement for assessing care quality is an emerging area, a system for measuring the quality of cancer care at the hospital level has not been well developed. The purpose of this study was to develop organization-based core measures for colorectal cancer patient care and apply these measures to compare hospital performance. Methods The development of core measures for colorectal cancer has undergone three stages including a modified Delphi method. Th...

  18. Studies on the optimization of leukemia and non-Hodgkin lymphoma therapies using opioids, chemotherapy and radioimmunotherapy; Studien zur Optimierung von Leukaemie- und non-Hodgkin-Lymphom-Therapien durch den Einsatz von Opioiden, Chemotherapeutika und Radioimmuntherapien

    Energy Technology Data Exchange (ETDEWEB)

    Roscher, Mareike

    2013-05-24

    Despite complex treatment schedules for cancer, the occurrence of resistances and relapses is a major concern in oncology. Hence, novel treatment options are needed. In this thesis, different approaches using radioimmunotherapy and the opioid D,L-methadone alone or in combination with doxorubicin were analyzed regarding their cytotoxic potential and the triggered signalling pathways in sensitive and resistant leukaemia and non-Hodgkin lymphoma (NHL). The radioimmunoconjugates [Bi-213]anti-CD33 and [Bi-213]anti-CD20 for treatment of acute myeloid leukaemia (AML) or NHL, respectively, were applied exemplary for the use of targeted alpha-therapies (TAT). Depending on the analyzed cell lines, the used activity concentrations and specific activities (MBq/μg antibody) apoptosis was induced abrogating radio- and chemo-cross-resistances specifically. The cell death was caspase-dependent activating the mitochondrial pathway and was executed by downregulation of the anti-apoptotic proteins XIAP and Bcl-xL. D,L-Methadone induces apoptosis in vitro and in vivo in opioid-receptor (OR) expressing cells depending on the OR density and the used concentrations. Resistances could be overcome and proliferation was inhibited. In combination with doxorubicin, a synergistic effect regarding cytotoxicity in ex vivo patient cells and cell lines was observed. This effect depends on the increase of doxorubicin uptake co-administering D,L-methadone whereas doxorubicin enhances OR expression. The activation of OR leads to the downregulation of cAMP playing a pivotal role in apoptosis induction. In vivo, the therapeutic potential of D,L-methadone alone or in combination with doxorubicin could be proven as mice transplanted with human T-ALL-cells could be identified as tumour free. In summary, these studies show that TAT using [Bi-213]anti-CD33 and [Bi-213]anti-CD20 as well as the opioid D,L-methadone harbour the potential to optimize conventional treatment modalities for leukaemia and NHL.

  19. Physicists develop more powerful tools to combat cancer

    CERN Document Server

    Antonella Del Rosso and Fabio Capello

    2012-01-01

    The tools physicists are currently sharing with doctors to defeat cancer are high-tech sensors for early detection and particles for use as sharp projectiles. The latest advances in medical physics and some of the most sophisticated devices for imaging, monitoring and treatment were presented at the ICTR-PHE 2012 conference. They will shape the future of advanced healthcare.   @font-face { font-family: "Cambria Math"; }@font-face { font-family: "Cambria"; }p.MsoNormal, li.MsoNormal, div.MsoNormal { margin: 0cm 0cm 0.0001pt; font-size: 12pt; font-family: Cambria; }p.MsoCommentText, li.MsoCommentText, div.MsoCommentText { margin: 0cm 0cm 0.0001pt; font-size: 10pt; font-family: Cambria; }span.MsoCommentReference { }a:link, span.MsoHyperlink { color: blue; text-decoration: underline; }a:visited, span.MsoHyperlinkFollowed { color: purple; text-decoration: underline; }span.CommentTextChar { }.MsoChpDefault { font-size: 10pt; font-family: Cambria; }div.WordSection1 { page: WordSection1; } So...

  20. Childhood cancer in developing society: A roadmap of health care

    Directory of Open Access Journals (Sweden)

    P M Ramesh

    2011-01-01

    Full Text Available Background: We assessed referral patterns of children with hematological malignancies (HM in North India. Materials and Methods: The parents/guardians were interviewed at presentation, in the period between October 2001 and November 2002. Patient delay (symptom-contact, health system delay (contact-diagnosis, total delay (symptom-diagnosis, and number of contacts were compared between high- and standard-risk disease group. Results: Of the 79 children (55 boys; 69.6% with HM, 47 (59.5% had Acute Lymphoblastic Leukemia (ALL. Forty-four children had high-risk disease. The patient, system and total delay were a median of 2 days (with Interquartile range IQR of 1−6, 37 days (IQR 13−55, and 38 days (IQR 15−60 respectively. Majority of patients (64/79; 81% went to private sector (non governmental health care providers for health care. Number of contacts, which was the most significant, correlate with system delay. Conclusions: Sensitizing the private sector practitioners about cancer in symptomatic children (pallor, bleeding, fever may be effective.

  1. Development magnet for portable MRI device: Investigate skin cancer

    Science.gov (United States)

    Dogan, Nurcan

    2013-03-01

    Nuclear magnetic resonance (NMR) is well known from diagnostic medical imaging and analytical chemical spectroscopy. The sample is brought into the laboratory to be investigated with radio-waves inside stationary magnets. This paper describes a new approach useful to reduce the gradient strength of the magnetic field. Despite of the recent progress in magnet design, homogeneity of permenant magnet is still very limited. Fortunately for medical applications usually there is need in high-field homogeneity to obtain the high-resolution spectra that provide the detailed chemical shift and coupling-constant. In this work we discuss various permanent magnet design-without cooling system- for magnetic imaging. The magnet used for the present application consists of two units. The main unit is built from static magnet blocks and generates the main magnetic field. The second one is the shim unit. It consists of smaller movable magnets used to correct in a controlled manner the magnetic field generated by the main unit. By combining the two units, magnetic fields with defined spatial dependence can be generated with high accuracy. The performance of the magnet in terms of resolution and sensitivity is first evaluated and compared with conventional other magnets of higher gradient strength using phantoms of known geometry and relaxation times. After integration of magnet with spectrometer, Our new system is used to profile the structures of healty and unhealthy (cancer) human skins in vivo. To understand the contrast between the different skin type, the distribution of relaxation times T1 is spatially investigated.

  2. Developing community based rehabilitation for cancer survivors: Organizing for coordination and coherence in practice

    DEFF Research Database (Denmark)

    la Cour, Karen; Cutchin, Malcolm

    2013-01-01

    Background. Increasing incidence of cancer combined with prolonged survival have raised the need for developing community based rehabilitation. The objectives of the analysis were to describe and interpret the key issues related to coordination and coherence of community-based cancer rehabilitation......-based organization, and informal relationships were fundamental for developing coordination and coherence. Conclusions. Coordination and coherence in community-based rehabilitation relies on increased collaboration, which may best be optimized by use of shared frameworks within and across systems. Results highlight...... the challenges faced in practical implementation of community rehabilitation and point to possible strategies for its enhancement....

  3. MET targeted therapy for lung cancer: clinical development and future directions

    Directory of Open Access Journals (Sweden)

    Feng Y

    2012-08-01

    Full Text Available Yan Feng,1,2 Patrick C Ma1–31Translational Hematology and Oncology Research, 2Solid Tumor Oncology, 3Aerodigestive Oncology Translational Research, Cleveland Clinic Taussig Cancer Institute, Cleveland, OH, USAAbstract: MET, the receptor for hepatocyte growth factor, has been identified as a novel promising target in various human malignancies, including lung cancer. Research studies have demonstrated that MET signaling plays important physiologic roles in embryogenesis and early development, whereas its deregulation from an otherwise quiescent signaling state in mature adult tissues can lead to upregulated cell proliferation, survival, scattering, motility and migration, angiogenesis, invasion, and metastasis in tumorigenesis and tumor progression. The MET pathway can be activated through ligand (hepatocyte growth factor, HGF or MET receptor overexpression, genomic amplification, MET mutations, and alternative splicing. A number of novel therapeutic agents that target the MET/hepatocyte growth factor pathway have been tested in early-phase clinical studies with promising results. Phase III studies of MET targeting agents have recently been initiated. This paper will review the MET signaling pathway and biology in lung cancer, and the recent clinical development and advances of MET/hepatocyte growth factor targeting agents. Emphasis will be placed on discussing various unanswered issues and key strategies needed to optimize further clinical development of MET targeting personalized lung cancer therapy.Keywords: MET, HGF, lung cancer, targeted therapy

  4. A Review of the Recent Developments in Synthetic Anti-Breast Cancer Agents.

    Science.gov (United States)

    Singh, Parvesh; Ngcoya, Nomandla; Kumar, Vipan

    2016-01-01

    The perceptible decrease in the incidence of breast cancer in recent years has not influenced its societal and economic impact and it remains as the most commonly diagnosed malignancies among females. Recent reports of clinical trials in preventive settings suggested chemoprevention as an appealing strategy zeroing heavily on endocrine intervention using selective estrogen receptor modulators (SERMs) and aromatase inhibitors (AIs). Unfortunately, these drugs are only effective in prevention of endocrine responsive lesions with essentially no effect in reducing the risk of estrogen-negative breast cancer. Further, the existing drugs for breast cancer treatment are invariably associated with several drawbacks such as poor oral bioavailability, non-selectivity and poor pharmacodynamics properties, limiting their clinical utility. Thus, the identification of new molecular targets and the development of agents with better pharmacological profiles will streamline the development of rational, effective and safe anticancer drugs with minimal side-effects. Over the past few years, different research groups have been actively involved in the design and synthesis of novel anti-breast cancer agents. In this review article, the recent developments (2013 onwards) made in the direction of synthesis of new scaffolds with promising anti-breast cancer activity, are briefly described. Hopefully, the data compiled in this article will update scientific community with recent endeavors in this field, and will certainly be encouraging for further research in this direction. PMID:26584726

  5. Development of Foot Massage Program on Nausea and Vomiting for Cancer Patients: A Literature Review

    Directory of Open Access Journals (Sweden)

    Ni Ketut Guru Prapti

    2012-08-01

    Full Text Available Objective: This study aims to develop a foot massage program to support care activity in reducing nausea and vomiting for cancer patients undergoing chemotherapy. Two phases, a literature review and the development of a foot massage program were conducted. The literature review was to analyze state of the art massage techniques by reviewing problems, related theories and supporting evidence. Method: Eight published studies in the English language were reviewed. A massage can be performed for different durations, from 10 minutes up to 60 minutes for three to six weeks and can be applied on various body areas. We found that the soft stroke/effleurage seems to be the best method and is most suitable for patients with cancer. It is also evident that foot massaging can be applied as a modality to reduce nausea and vomiting for cancer patients undergoing chemotherapy. Result: We developed a foot massage program specifically for patients with cancer. The foot massage program comprised of three sessions, including 1 education session, 2 preparation session, and 3 foot massage session. In the education session, patients obtain brief information about the definition of a foot massage, the benefits and contraindication of foot massaging. During the preparation phase, foot soaking and warming up are performed. Subsequently, the foot massage is applied and should last for 30 minutes. Further research is recommended to test the effectiveness of the proposed foot massage program for nausea and vomiting in cancer patients across countries including Indonesia. Key Words: Foot massage program, chemotherapy, nausea and vomiting

  6. Glycosylation of Glycolipids in Cancer: Basis for Development of Novel Therapeutic Approaches

    Directory of Open Access Journals (Sweden)

    JoseLuisDaniotti

    2013-12-01

    Full Text Available Altered networks of gene regulation underlie many pathologies, including cancer. There are several proteins in cancer cells that are turned either on or off, which dramatically alters the metabolism and the overall activity of the cell, with the complex machinery of enzymes involved in the metabolism of glycolipids not being an exception. The aberrant glycosylation of glycolipids on the surface of the majority of cancer cells, associated with increasing evidence about the functional role of these molecules in a number of cellular physiological pathways, has received considerable attention as a convenient immunotherapeutic target for cancer treatment. This has resulted in the development of a substantial number of passive and active immunotherapies, which have shown promising results in clinical trials. More recently, antibodies to glycolipids have also emerged as an attractive tool for the targeted delivery of cytotoxic agents, thereby providing a rationale for future therapeutic interventions in cancer. This review first summarizes the cellular and molecular bases involved in the metabolic pathway and expression of glycolipids, both in normal and tumor cells, paying particular attention to sialosylated glycolipids (gangliosides. The current strategies in the battle against cancer in which glycolipids are key players are then described.

  7. Developing a community-based intervention to improve quality of life in people with colorectal cancer: a complex intervention development study

    OpenAIRE

    Gray, N M; Allan, J.L.; Murchie, P; Browne, S; Hall, S.; Hubbard, G.; Johnston, M.; Lee, A.J.; McKinley, A.; Macleod, U; Presseau, J.; Samuel, L; Wyke, S; Campbell, N.C.

    2013-01-01

    Objectives To develop and pilot a theory and evidence-based intervention to improve quality of life (QoL) in people with colorectal cancer. Design A complex intervention development study. Setting North East Scotland and Glasgow. Participants Semistructured interviews with people with colorectal cancer (n=28), cancer specialists (n=16) and primary care health professionals (n=14) and pilot testing with patients (n=12). Interventions A single, 1 h nurse home visit 6–12 week...

  8. Drugs in development for treatment of patients with cancer-related anorexia and cachexia syndrome [Retraction

    OpenAIRE

    Mantovani G.; Madeddu C; Macciò A

    2013-01-01

     The Editor-in-Chief, Dr Pilch, of Drug Design, Development and Therapy has been alerted to unacceptable levels of duplication between a previously published paper: Macciò A, Madeddu C, Mantovani G. Current pharmacotherapy options for cancer anorexia and cachexia. Expert Opin. Pharmacotherapy 2012 13(17) 2453–2472 and one published subsequently in Drug Design, Development and Therapy: Mantovani G, Madeddu C, Macciò A. Drugs in development for treatment...

  9. Challenges to the development of antigen-specific breast cancer vaccines

    International Nuclear Information System (INIS)

    Continued progress in the development of antigen-specific breast cancer vaccines depends on the identification of appropriate target antigens, the establishment of effective immunization strategies, and the ability to circumvent immune escape mechanisms. Methods such as T cell epitope cloning and serological expression cloning (SEREX) have led to the identification of a number target antigens expressed in breast cancer. Improved immunization strategies, such as using dendritic cells to present tumor-associated antigens to T lymphocytes, have been shown to induce antigen-specific T cell responses in vivo and, in some cases, objective clinical responses. An outcome of successful tumor immunity is the evolution of antigen-loss tumor variants. The development of a polyvalent breast cancer vaccine, directed against a panel of tumor-associated antigens, may counteract this form of immune escape

  10. HtrA1 expression associated with the occurrence and development of esophageal cancer

    Directory of Open Access Journals (Sweden)

    Yu Youtao

    2012-08-01

    Full Text Available Abstract Background The purposes of this study were to measure both the mRNA and protein expression levels of high-temperature requirement serine peptidase 1 (HtrA1 in human esophageal cancer tissues and their adjacent, comparatively normal esophageal tissues. Methods The expression levels of HtrA1 mRNA and protein in both tissue types were measured by semi-quantitative RT-PCR (reverse transcription-polymerase chain reaction and Western blotting. The clinical and pathological correlation between HtrA1 expression levels and the occurrence and development of esophageal cancer was analyzed. Results The expression levels of HtrA1 mRNA and protein in esophageal carcinoma were significantly lower than the levels expressed in their adjacent normal esophageal tissue (p p p p  Conclusions HtrA1 expression is associated with the occurrence and development of esophageal cancer.

  11. From milk to malignancy: the role of mammary stem cells in development, pregnancy and breast cancer

    Institute of Scientific and Technical Information of China (English)

    Benjamin Tiede; Yibin Kang

    2011-01-01

    Adult stem cells of the mammary gland (MaSCs) are a highly dynamic population of cells that are responsible for the generation of the gland during puberty and its expansion during pregnancy, in recent years significant advances have been made in understanding how these cells are regulated during these developmentally important processes both in humans and in mice. Understanding how MaSCs are regulated is becoming a particularly important area of research, given that they may be particularly susceptible targets for transformation in breast cancer. Here, we summarize the identification of MaSCs, how they are regulated and the evidence for their serving as the origins of breast cancer, in particular, we focus on how changes in MaSC populations may explain both the increased risk of developing aggressive ERJPR(-) breast cancer shortly after pregnancy and the long-term decreased risk of developing ER/ PR(+) tumors.

  12. The role of natural polyphenols in cell signaling and cytoprotection against cancer development.

    Science.gov (United States)

    Lewandowska, Hanna; Kalinowska, Monika; Lewandowski, Włodzimierz; Stępkowski, Tomasz M; Brzóska, Kamil

    2016-06-01

    The cytoprotective and anticancer action of dietary in-taken natural polyphenols has for long been attributed only to their direct radical scavenging activities. Currently it is well supported that those compounds display a broad spectrum of biological and pharmacological outcomes mediated by their complex metabolism, interaction with gut microbiota as well as direct interactions of their metabolites with key cellular signaling proteins. The beneficial effects of natural polyphenols and their synthetic derivatives are extensively studied in context of cancer prophylaxis and therapy. Herein we focus on cell signaling to explain the beneficial role of polyphenols at the three stages of cancer development: we review the recent proceedings about the impact of polyphenols on the cytoprotective antioxidant response and their proapoptotic action at the premalignant stage, and finally we present data showing how phenolic acids (e.g., caffeic, chlorogenic acids) and flavonols (e.g., quercetin) hamper the development of metastatic cancer. PMID:27142731

  13. Life time risk for development of ten major cancers in India and its trends over the years 1982 to 2000

    Directory of Open Access Journals (Sweden)

    Satyanarayana L

    2008-02-01

    Full Text Available Background : Understanding cancer magnitude, risk and trends will be of help in cancer control programs. Aim : To study trends in cumulative risk up to 64 years of age as lifetime risk of developing major cancers in India during the years 1982 to 2000. Design : Retrospective. Setting : Secondary sources of cancer-registration data. Materials and Methods : Data on age-specific cancer-incidence rates were collected for patients 0-64 years of age of either sex for 10 major cancer sites from the National Cancer Registry Program (NCRP reports of India from Mumbai, Chennai, Bangalore, Bhopal and Delhi; and Barshi registries for the years 1982 or 1988 to 2000. Statistical Analysis : Cumulative risks computed for lifetime development of cancer. Linear trends were studied using simple linear regressions. Results : The lifetime risk among females for the10 cancer sites ranged from 0.02 to 3.3% and from 0.04 to 2.4% for the years 1982 and 2000 respectively; whereas among males, it ranged from 0.04 to 0.89% and from 0.05 to 0.95% respectively. Significant (P < 0.05 increasing trends were observed for breast, non-Hodgkin′s lymphoma (NHL, gallbladder, thyroid and ovary cancers among females; while declining trends were observed for cervix, mouth, stomach, esophagus and tongue cancers. Among males, significant (P < 0.05 increasing trends were observed for NHL and prostate cancer; whereas declining trends were observed for stomach, liver, hypopharynx and tongue cancers. Cancers of mouth and esophagus showed increasing trends (P < 0.05 in some regions and declining trends (P < 0.05 in some other. Conclusion : Significant and higher rates of positive trends in lifetime cancer risks for breast cancer among females and for NHL among both sexes were observed.

  14. Positional Variations in Mammary Gland Development and Cancer

    OpenAIRE

    Veltmaat, Jacqueline M.; Ramsdell, Ann F.; Sterneck, Esta

    2013-01-01

    Most mammals develop their mammary glands in pairs of which the two counterparts are symmetrically displaced away from the ventral midline. Based on this symmetry and the same functional outcome as a milk-producing organ, the mammary glands are easily presumed to be mere copies of one another. Based on our analysis of published data with inclusion of new results related to mammary development and pathology in mice, we argue that this presumption is incorrect: Between and within pairs, mammary...

  15. Mitigating the risk of radiation-induced cancers: limitations and paradigms in drug development

    International Nuclear Information System (INIS)

    The United States radiation medical countermeasures (MCM) programme for radiological and nuclear incidents has been focusing on developing mitigators for the acute radiation syndrome (ARS) and delayed effects of acute radiation exposure (DEARE), and biodosimetry technologies to provide radiation dose assessments for guiding treatment. Because a nuclear accident or terrorist incident could potentially expose a large number of people to low to moderate doses of ionising radiation, and thus increase their excess lifetime cancer risk, there is an interest in developing mitigators for this purpose. This article discusses the current status, issues, and challenges regarding development of mitigators against radiation-induced cancers. The challenges of developing mitigators for ARS include: the long latency between exposure and cancer manifestation, limitations of animal models, potential side effects of the mitigator itself, potential need for long-term use, the complexity of human trials to demonstrate effectiveness, and statistical power constraints for measuring health risks (and reduction of health risks after mitigation) following relatively low radiation doses (<0.75 Gy). Nevertheless, progress in the understanding of the molecular mechanisms resulting in radiation injury, along with parallel progress in dose assessment technologies, make this an opportune, if not critical, time to invest in research strategies that result in the development of agents to lower the risk of radiation-induced cancers for populations that survive a significant radiation exposure incident. (review)

  16. Melanin-targeting antibody as a potential agent for radioimmunotherapy of melanoma

    International Nuclear Information System (INIS)

    Aim: Melanoma is a cancer of increasing incidence for which new methods of treatment and imaging are urgently needed. Currently there is no effective therapy for metastatic melanoma as this tumor is resistant to radiation and chemotherapy. The majority of human melanomas are pigmented with melanin. Here we investigated the possibility of using a melanin-binding antibody (mAb 6D2) which was originally developed against fungal melanin as a delivery vehicle for RIT of pigmented melanoma. Materials and Methods: MAb 6D2 (IgM type) was generated from hybridomas obtained from mice immunized with melanin isolated from Cryptococcus neoformans. The mAb was radiolabeled with 213Bi or 111In via bifunctional chelator CHXA'' and with 188Re - via 'direct labeling'. The immunoreactivity of radiolabeled 6D2 mAb towards fungal melanin was tested by immunofluorescence. Cell binding of 213Bi-6D2, 188Re-6D2 and irrelevant IgM 12A1 was evaluated by incubating 2 μg/mL mAb with 0.23-2 x 106 human slightly pigmented melanoma cells SK-28-MEL (whole or lysed) which were grown with or without 110 μM L-tyrosine to promote melanin formation. In vivo binding of 111In-6D2 was studied by scintigraphic imaging in nude mice injected IP with 2.8 x 106 SK-28-MEL cells 24 h before 111In-6D2; biodistribution of 188Re-6D2 was performed in nude mice bearing SK-28-MEL xenografted tumors. Results: The immunoreactivity of radiolabeled 6D2 mAb to melanin was demonstrated by immunofluorescence. Cell binding of 213Bi-6D2 and 188Re-6D2 was higher for the melanoma cells grown with 110 μM L-tyrosine suggesting melanin-specific binding. There was no significant difference (P>0.05) in binding to the whole or lysed cells which may be due to reactivity with melanin or precursors found on the cell surface. In mice injected IP with SK-28-MEL cells there was more retention of 111In-6D2 in intraperitoneal cavity compared to irrelevant 111In-IgM and control animals with no tumor cells. The biodistribution of 188Re-6D2 m

  17. Overexpression of truncated ERG from TMPRSS2-ERG fusion and prostate cancer development

    Directory of Open Access Journals (Sweden)

    Melanie Leong

    2009-09-01

    Full Text Available Melanie Leong1*, Wen-feng Shi2*, Jun Tian2, Ellen Cho1, Abbas Raza1, Saquib A Siddiqi1, Abdulhafez Selim3, Han-chun Chen4, Dianzheng Zhang1,41Department of Biochemistry and Molecular Biology and Center for Chronic Disorders of Aging, Philadelphia College of Osteopathic Medicine, Philadelphia, PA, USA; 2Department of Renal Transplantation, Qilu Hospital of Shandong University, Jinan, Shandong, People’s Republic of China; 3Osteotech Inc, Eatontown, NJ, USA; 4Department of Biochemistry, School of Biological Science and Technology, Central South University, Changsha, Hunan, People’s Republic of China; *These authors contributed equally to this workAbstract: In men, prostate cancer is one of the most common cancers worldwide and the second leading cause of death among all cancer types in Europe and North America, with the numbers of those affected continuing to increase. Recent studies have identified a recurrent fusion of TMPRSS2 with members of the ETS family of transcription factors in about 80% of prostate cancer tissues. Among them, the TMPRSS2-ERG fusion accounts for approximately 50% of these cases. TMPRSS2 is highly regulated by androgen receptor and the chromosomal rearrangement abnormally induces ERG production by androgen. To investigate the effects of ERG overexpression on its target genes expression and prostate cancer development, plasmids were first constructed by inserting the truncated ERG into an expression vector in the forward or reverse directions. A predicted three-dimensional model of the protein structure of the truncated ERG, along with immunofluorescence assays, suggest that the minor deletion on the N-terminus does not appear to affect the structure or function of ERG. Results from ERG target gene expression profile indicate that TMPRSS2-ERG fusion-induced aberrant ERG overexpression is likely involved in prostate cancer development by enhancing tumor angiogenesis.Keywords: prostate cancer, androgen receptor, TMPRSS2

  18. Development and characterization of multifunctional nanoparticles for drug delivery to cancer cells

    Science.gov (United States)

    Nahire, Rahul Rajaram

    Lipid and polymeric nanoparticles, although proven to be effective drug delivery systems compared to free drugs, have shown considerable limitations pertaining to their uptake and release at tumor sites. Spatial and temporal control over the delivery of anticancer drugs has always been challenge to drug delivery scientists. Here, we have developed and characterized multifunctional nanoparticles (liposomes and polymersomes) which are targeted specifically to cancer cells, and release their contents with tumor specific internal triggers. To enable these nanoparticles to be tracked in blood circulation, we have imparted them with echogenic characteristic. Echogenicity of nanoparticles is evaluated using ultrasound scattering and imaging experiments. Nanoparticles demonstrated effective release with internal triggers such as elevated levels of MMP-9 enzyme found in the extracellular matrix of tumor cells, decreased pH of lysosome, and differential concentration of reducing agents in cytosol of cancer cells. We have also successfully demonstrated the sensitivity of these particles towards ultrasound to further enhance the release with internal triggers. To ensure the selective uptake by folate receptor- overexpressing cancer cells, we decorated these nanoparticles with folic acid on their surface. Fluorescence microscopic images showed significantly higher uptake of folate-targeted nanoparticles by MCF-7 (breast cancer) and PANC-1 (pancreatic cancer) cells compared to particles without any targeting ligand on their surface. To demonstrate the effectiveness of these nanoparticles to carry the drugs inside and kill cancer cells, we encapsulated doxorubicin and/or gemcitabine employing the pH gradient method. Drug loaded nanoparticles showed significantly higher killing of the cancer cells compared to their non-targeted counterparts and free drugs. With further development, these nanoparticles certainly have potential to be used as a multifunctional nanocarriers for image

  19. Using intervention mapping to develop a work-related guidance tool for those affected by cancer

    Directory of Open Access Journals (Sweden)

    Munir Fehmidah

    2013-01-01

    Full Text Available Abstract Background Working-aged individuals diagnosed and treated for cancer require support and assistance to make decisions regarding work. However, healthcare professionals do not consider the work-related needs of patients and employers do not understand the full impact cancer can have upon the employee and their work. We therefore developed a work-related guidance tool for those diagnosed with cancer that enables them to take the lead in stimulating discussion with a range of different healthcare professionals, employers, employment agencies and support services. The tool facilitates discussions through a set of questions individuals can utilise to find solutions and minimise the impact cancer diagnosis, prognosis and treatment may have on their employment, sick leave and return to work outcomes. The objective of the present article is to describe the systematic development and content of the tool using Intervention Mapping Protocol (IMP. Methods The study used the first five steps of the intervention mapping process to guide the development of the tool. A needs assessment identified the ‘gaps’ in information/advice received from healthcare professionals and other stakeholders. The intended outcomes and performance objectives for the tool were then identified followed by theory-based methods and an implementation plan. A draft of the tool was developed and subjected to a two-stage Delphi process with various stakeholders. The final tool was piloted with 38 individuals at various stages of the cancer journey. Results The tool was designed to be a self-led tool that can be used by any person with a cancer diagnosis and working for most types of employers. The pilot study indicated that the tool was relevant and much needed. Conclusions Intervention Mapping is a valuable protocol for designing complex guidance tools. The process and design of this particular tool can lend itself to other situations both occupational and more health

  20. Radiotherapy in cancer treatment: Present status, realizable clinical advances, and further development trends in radiooncology

    International Nuclear Information System (INIS)

    Many decades of local cancer therapy have led to the present balance that 35% of all patients can be cured by local measures. Half of the successful cancer treatments are due to high-voltage therapy. With improved local measures, the near future might see a further increase in the cancer healing rate. Surgical treatment has probably reached its limits by now, but further developments in cancer radiotherapy and radiocurability are already in sight. With an optimum development of local cancer therapy, therapy might be successful in more than 50% of all cases. The superiority of radiotherapy with fast neutrons has been clinically proven, and it has become generally applicable by the introduction of neutron generators. Negative pions are extremely expensive and difficult to produce and biologically inferior to fast neutrons. Still, it is possible that they may be used in tumour therapy for a limited range of applications in rare and complex situations in tumour therapy. The application of so-called electron-affine substances of the nitroidimazole type has highly improved the radiocurability of many different tumours in animal experiments. (orig./MG)

  1. Development testing of mobile health interventions for cancer patient self-management: A review.

    Science.gov (United States)

    Darlow, Susan; Wen, Kuang-Yi

    2016-09-01

    As the vision of mobile health (mHealth) is beginning to be realized, rigorous intervention development protocols are needed in order to draw optimal efficacy and effectiveness to support patient-centered oncology care. The purpose of the current study was to conduct a review of published articles that describe the development process of mHealth interventions for patients' cancer care self-management. The review search yielded 11 interventions, reported by 14 manuscripts. The following trends emerged: importance of stakeholder engagement during the development process, addressing the unique needs and experiences of cancer patients and care providers, ensuring user satisfaction with the system, and identifying perceived benefits and limitations of the system. This review provides practical suggestions for mHealth intervention development. Assessments of user perceptions should be both qualitative and quantitative, and researchers should follow an established framework when developing a randomized controlled trial employing mHealth. PMID:25916831

  2. Up-regulation of microRNA-10b is associated with the development of breast cancer brain metastasis

    OpenAIRE

    Ahmad, Aamir; Sethi, Seema; Chen, Wei; Ali-Fehmi, Rouba; Mittal, Sandeep; Fazlul H. Sarkar

    2014-01-01

    Brain metastases from primary breast cancer are difficult to treat and associated with poor prognosis. Our understanding of the molecular basis for the development of such cancers is sparse. We hypothesized that the pro-metastatic microRNA-10b (miR-10b) plays a role in breast cancer brain metastasis. The study cohort comprised of twenty patients with breast cancer and brain metastasis as well as ten control patients (age, stage, and follow-up matched) with breast cancer without brain metastas...

  3. Diverse pathomechanisms leading to the breakdown of cellular estrogen surveillance and breast cancer development: new therapeutic strategies

    OpenAIRE

    Suba Z

    2014-01-01

    Zsuzsanna SubaNational Institute of Oncology, Budapest, HungaryAbstract: Recognition of the two main pathologic mechanisms equally leading to breast cancer development may provide explanations for the apparently controversial results obtained by sexual hormone measurements in breast cancer cases. Either insulin resistance or estrogen receptor (ER) defect is the initiator of pathologic processes and both of them may lead to breast cancer development. Primary insulin resistance induces hyperand...

  4. Harnessing information and communication technologies to leverage scarce resources for cancer education, research and practice in developing countries

    OpenAIRE

    Andela Valentine B

    2006-01-01

    Abstract In developing countries, low levels of awareness, cost and organizational constraints on access to specialized care contribute to inadequate patient help-seeking behavior. As much as 95% of cancer patients in developing countries are diagnosed at late to end stage disease. Consequently, treatment outcome is dismally poor and a vicious cycle sets in, with public mystification of cancer and the admonishment of cancer medicine as a futile effort, all, to the further detriment of patient...

  5. The initial development of the 'Cancer Caregiving Tasks, Consequences and Needs Questionnaire' (CaTCoN)

    DEFF Research Database (Denmark)

    Lund, Line; Ross, Lone; Grønvold, Mogens

    2012-01-01

    To develop a questionnaire for cancer patients' informal caregivers, measuring the caregiving tasks and consequences, and the caregivers' needs with a main focus on the interaction with the health care professionals. Such an instrument is needed to evaluate the efforts directed towards caregivers...

  6. Developing a Culturally Responsive Breast Cancer Screening Promotion with Native Hawaiian Women in Churches

    Science.gov (United States)

    Kaopua, Lana Sue

    2008-01-01

    This article presents findings from research to develop the promotional component of a breast cancer screening program for Native Hawaiian women associated with historically Hawaiian churches in medically underserved communities. The literature on adherence to health recommendations and health promotions marketing guided inquiry on screening…

  7. Ion channels and transporters in the development of drug resistance in cancer cells

    DEFF Research Database (Denmark)

    Hoffmann, Else Kay; Lambert, Ian Henry

    2014-01-01

    Multi-drug resistance (MDR) to chemotherapy is the major challenge in the treatment of cancer. MDR can develop by numerous mechanisms including decreased drug uptake, increased drug efflux and the failure to undergo drug-induced apoptosis. Evasion of drug-induced apoptosis through modulation of ion...

  8. List of gene variants developed for cancer cells from nine tissue types

    Science.gov (United States)

    NCI scientists have developed a comprehensive list of genetic variants for each of the types of cells that comprise what is known as the NCI-60 cell line collection. This new list adds depth to the most frequently studied human tumor cell lines in cancer

  9. Developing a Cancer Prevention Programme for African-American Daughters and Mothers

    Science.gov (United States)

    Annang, Lucy; Spencer, S. Melinda; Jackson, Dawnyéa; Rosemond, Tiara N.; Best, Alicia L.; Williams, Leah R.; Carlos, Bethany

    2015-01-01

    Objective: To describe how nominal group technique was used to inform the development of a breast and cervical cancer awareness programme for African-American adult daughters and mothers. Design: A qualitative approach using nominal group technique. Setting: A mid-sized city in the Southern USA. Method: Nominal group technique was used with 30…

  10. Development of a Brief Survey on Colon Cancer Screening Knowledge and Attitudes Among Veterans

    Directory of Open Access Journals (Sweden)

    Franklin Medio, PhD

    2005-03-01

    Full Text Available Introduction Poor knowledge of and negative attitudes toward available screening tests may account in part for colorectal cancer screening rates being the lowest among 17 quality measures reported for the Department of Veterans Affairs health care system, the largest integrated health system in the United States. The purpose of this study was to develop a brief assessment tool to evaluate knowledge and attitudes among veterans toward colorectal cancer screening options. Methods A 44-item questionnaire was developed to assess knowledge, attitudes, and beliefs about colorectal cancer and screening and was then administered as part of an ongoing randomized controlled trial among 388 veterans receiving care in a general medicine clinic. Sixteen candidate items on colorectal cancer knowledge, attitudes, and beliefs were selected for further evaluation using principal components analysis. Two sets of items were then further analyzed. Results Because the Cronbach a for beliefs was low (a = 0.06, the beliefs subscale was deleted from further consideration. The final scale consisted of seven items: a four-item attitude subscale (a = 0.73 and a three-item knowledge subscale (a = 0.59. Twelve-month follow-up data were used to evaluate predictive validity; improved knowledge and attitudes were significantly associated with completion of flexible sigmoidoscopy (P = .004 and completion of either flexible sigmoidoscopy or colonoscopy (P = .02. Conclusion The two-factor scale offers a parsimonious and reliable measure of colorectal cancer screening knowledge and attitudes among veterans. This colorectal Cancer Screening Survey (CSS may especially be useful as an evaluative tool in developing and testing of interventions designed to improve screening rates within this population.

  11. The characteristics of human antibody targeting the Epidermal Growth Factor Receptor in vivo for radioimmunotherapy in a small animal model

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Eun Jung; Choi, Tae Hyun; Kim, Byoung Soo; Cheon, Gi Jeong [Korea Institue of Radiological and Medical Sciences, Seoul (Korea, Republic of); Hong, Kwang Won; Chang, Ki Hwan; Shin, Yong Won; Ryoo, Kyung Hwan; Shin, Yong Nam; Kim, Se Ho [Green Cross Corp., Yongin (Korea, Republic of)

    2010-05-15

    The identification of epidermal growth factor receptor (EGFR) as an oncogene has led to the development of anticancer therapeutics directed against EGFR, including Erbitux for colon cancer. Many therapeutic approaches are aimed at the EGFR. Erbitux is example of monoclonal antibody inhibitors. The monoclonal antibodies block the extracellular ligand binding domain. EGFR4-2, IgG human monoclonal antibody, has been developed on the basis of human antibody gene library in Green Cross Corp. Small animal imaging is useful for preclinical evaluation of radiolabeled antibody to see biodistribution and targeting ability at serial time points in same animals

  12. Role of JNK in mammary gland development and breast cancer

    OpenAIRE

    Cellurale, Cristina; Girnius, Nomeda; Jiang, Feng; Cavanagh-Kyros, Julie; Lu, Shaolei; Garlick, David S.; Mercurio, Arthur M.; Davis, Roger J

    2011-01-01

    JNK signaling has been implicated in the developmental morphogenesis of epithelial organs. In this study we employed a compound deletion of the murine Jnk1 and Jnk2 genes in the mammary gland to evaluate the requirement for these ubiquitously expressed genes in breast development and tumorigenesis. JNK1/2 was not required for breast epithelial cell proliferation or motility. However, JNK1/2 deficiency caused increased branching morphogenesis and defects in the clearance of lumenal epithelial ...

  13. Mammary development and breast cancer: the role of stem cells

    OpenAIRE

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

    2011-01-01

    The mammary gland is a highly regenerative organ that can undergo multiple cycles of proliferation, lactation and involution, a process controlled by stem cells. The last decade much progress has been made in the identification of signaling pathways that function in these stem cells to control self-renewal, lineage commitment and epithelial differentiation in the normal mammary gland. The same signaling pathways that control physiological mammary development and homeostasis are also often fou...

  14. Developing and evaluating a simple, spreadsheet-based pathology report extraction system for cancer registrars.

    Science.gov (United States)

    Liang, Ya-Fen; Chu, Pei-Yi; Chang, Cheng-Shyong; Wang, Chen-Hsi; Chang, Polun

    2006-01-01

    Surgical pathology reports are essential for cancer registry. However, cancer registrars in Taiwan still code manually from the pathology reports written in unstructured free-text. The purpose of this study was to develop a cost-effective tool to automatically code the free-text reports with Microsoft-û Excel VBA too. The time and accuracy performances between these two approaches were compared. Results showed that the cost-effectiveness and time-saving of the system and the potentials of using spreadsheet tools for healthcare professionals. PMID:17238627

  15. Buried penis: An unrecognized risk factor in the development of invasive penile cancer

    OpenAIRE

    Abdulla, Alym; Daya, Dean; Pinthus, Jehonathan; Davies, Timothy

    2012-01-01

    One of the documented benefits of neonatal circumcision is protection against invasive penile cancer. To date there have been a handful of published cases of invasive penile cancer in men circumcised as neonates. We report a case of a 73-year-old man, with a history of neonatal circumcision with no evidence of previous human papillomavirus exposure, who developed a buried penis secondary to obesity. He was diagnosed with Grade 2, pT3N0 squamous cell carcinoma of the penis. This report suggest...

  16. Review and analysis of external quality assessment of breast cancer services in Europe: Supporting information for the development of a European Quality Assurance scheme for Breast Cancer Services

    OpenAIRE

    DEANDREA SILVIA; LERDA Donata; LOPEZ ALCALDE JESUS; NEAMTIU LUCIANA; SAZ PARKINSON ZULEIKA ESTHER; ULUTURK ASLI

    2015-01-01

    The JRC, the European Commission’s in-house science service, was assigned in December 2012 with the tasks of (i) developing a new version of the European guidelines for breast cancer screening and diagnosis (in the following mentioned as 'the new European Guidelines') and of (ii) developing a voluntary European Quality Assurance scheme for breast cancer services based on the European legislative framework on accreditation (defined in Regulation (EC) No 765/2008) (in the following mentioned as...

  17. Development of personalized treatments in lung cancer: focusing on the EGFR mutations and beyond

    Directory of Open Access Journals (Sweden)

    Suda K

    2013-08-01

    Full Text Available Kenichi Suda,1,2 Tetsuya Mitsudomi1 1Division of Thoracic Surgery, Department of Surgery, Kinki University Faculty of Medicine, Osaka-Sayama, Japan; 2Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan Abstract: Lung cancers with epidermal growth factor receptor (EGFR gene mutation account for ~40% of adenocarcinoma in East Asians and ~15% of that in Caucasians, which makes them one of the most common molecularly defined lung cancer subsets. The role of EGFR mutation as a strong predictive biomarker of response to EGFR-tyrosine kinase inhibitors (TKIs was finally confirmed by the biomarker analysis of Iressa Pan-Asian Study (IPASS. Since the 2004 discovery of EGFR mutation in lung cancer, the EGFR mutation and EGFR-TKI treatment have been widely studied. These include characteristics of lung cancers with EGFR mutations; clinical efficacies and adverse effects of EGFR-TKIs in patients with EGFR-mutated lung cancers; development of novel EGFR-TKIs that may prolong progression-free survival of these patients or overcome resistance to first-generation EGFR-TKIs (gefitinib and erlotinib; optimal treatment schedules for EGFR-TKIs to delay emergence of resistance; molecular mechanisms of acquired resistance to EGFR-TKIs; treatment strategies after patients acquire resistance to EGFR-TKIs; and predictive biomarkers for EGFR-TKIs among patients with EGFR-mutated lung cancers. Some of these results are widely accepted, while others are apparent only in cell line models, preclinical animal models, or retrospective analyses (and sometimes conflict with each other. In this review, we summarize accumulated reports from the past decade, especially focusing on unanswered but important clinical questions in treating patients with EGFR-mutated lung cancers. Keywords: epidermal growth factor receptor mutation, predictive biomarkers, personalized therapy, molecular target, adjuvant therapy, acquired resistance

  18. Affinity peptide developed by phage display selection for targeting gastric cancer

    Institute of Scientific and Technical Information of China (English)

    Wen-Jie Zhang; Yan-Xia Sui; Arun Budha; Jian-Bao Zheng; Xue-Jun Sun; Ying-Chun Hou; Thomas D Wang; Shao-Ying Lu

    2012-01-01

    AIM:To develop an affinity peptide that binds to gastric cancer used for the detection of early gastric cancer.METHODS:A peptide screen was performed by biopanning the PhD-12 phage display library,clearing non-specific binders against tumor-adjacent normal appearing gastric mucosa and obtaining selective binding against freshly harvested gastric cancer tissues.Tumortargeted binding of selected peptides was confirmed by bound phage counts,enzyme-linked immunosorbent assay,competitive inhibition,fluorescence microscopy and semi-quantitative analysis on immunohistochemistry using different types of cancer tissues.RESULTS:Approximately 92.8% of the non-specific phage clones were subtracted from the original phage library after two rounds of biopanning against normalappearing gastric mucosa.After the third round of positive screening,the peptide sequence AADNAKTKSFPV (AAD) appeared in 25% (12/48) of the analyzed phages.For the control peptide,these values were 6.8 ± 2.3,5.1 ± 1.7,3.5 ± 2.1,4.6 ± 1.9 and 1.1 ± 0.5,respectively.The values for AAD peptide were statistically significant (P < 0.01) for gastric cancer as compared with other histological classifications and control peptide.CONCLUSION:A novel peptide is discovered to have a specific binding activity to gastric cancer,and can be used to distinguish neoplastic from normal gastric mucosa,demonstrating the potential for early cancer detection on endoscopy.

  19. Bio-effect model applied to {sup 131}I radioimmunotherapy of refractory non-Hodgkin's lymphoma

    Energy Technology Data Exchange (ETDEWEB)

    Roberson, Peter L.; Amro, Hanan; Schipper, Matthew J. [University of Michigan, Department of Radiation Oncology, Ann Arbor, MI (United States); Wilderman, Scott J.; Avram, Anca M.; Dewaraja, Yuni K. [University of Michigan Medical Center, Department of Radiology, Ann Arbor, MI (United States); Kaminski, Mark S. [University of Michigan Medical Center, Division of Hematology and Oncology, Department of Internal Medicine, Ann Arbor, MI (United States)

    2011-05-15

    Improved data collection methods have improved absorbed dose estimation by tracking activity distributions and tumor extent at multiple time points, allowing individualized absorbed dose estimation. Treatment with tositumomab and {sup 131}I-tositumomab anti-CD20 radioimmunotherapy (BEXXAR) yields a cold antibody antitumor response (cold protein effect) and a radiation response. Biologically effective contributions, including the cold protein effect, are included in an equivalent biological effect model that was fit to patient data. Fifty-seven tumors in 19 patients were followed using 6 single proton emission computed tomography (SPECT)/CT studies, 3 each post tracer (5 mCi) and therapy ({proportional_to}100 mCi) injections with tositumomab and {sup 131}I-tositumomab. Both injections used identical antibody mass, a flood dose of 450 mg plus 35 mg of {sup 131}I tagged antibody. The SPECT/CT data were used to calculate absorbed dose rate distributions and tumor and whole-body time-activity curves, yielding a space-time dependent absorbed dose rate description for each tumor. Tumor volume outlines on CT were used to derive the time dependence of tumor size for tracer and therapy time points. A combination of an equivalent biological effect model and an inactivated cell clearance model was used to fit absorbed dose sensitivity and cold effect sensitivity parameters to tumor shrinkage data, from which equivalent therapy values were calculated. Patient responses were categorized into three groups: standard radiation sensitivity with no cold effect (7 patients), standard radiation sensitivity with cold effect (11 patients), and high radiation sensitivity with cold effect (1 patient). Fit parameters can be used to categorize patient response, implying a potential predictive capability. (orig.)

  20. Bismuth-212-labeled anti-Tac monoclonal antibody: alpha-particle-emitting radionuclides as modalities for radioimmunotherapy

    International Nuclear Information System (INIS)

    Anti-Tac, a monoclonal antibody directed to the human interleukin 2 (IL-2) receptor, has been successfully conjugated to the alpha-particle-emitting radionuclide bismuth-212 by use of a bifunctional ligand, the isobutylcarboxycarbonic anhydride of diethylenetriaminepentaacetic acid. The physical properties of 212Bi are appropriate for radioimmunotherapy in that it has a short half-life, deposits its high energy over a short distance, and can be obtained in large quantities from a radium generator. Antibody specific activities of 1-40 microCi/microgram (1 Ci = 37 GBq) were achieved. Specificity of the 212Bi-labeled anti-Tac was demonstrated for the IL-2 receptor-positive adult T-cell leukemia line HUT-102B2 by protein synthesis inhibition and clonogenic assays. Activity levels of 0.5 microCi or the equivalent of 12 rad/ml of alpha radiation targeted by anti-Tac eliminated greater than 98% the proliferative capabilities of HUT-102B2 cells with more modest effects on IL-2 receptor-negative cell lines. Specific cytotoxicity was blocked by excess unlabeled anti-Tac but not by human IgG. In addition, an irrelevant control monoclonal antibody of the same isotype labeled with 212Bi was unable to target alpha radiation to cell lines. Therefore, 212Bi-labeled anti-Tac is a potentially effective and specific immunocytotoxic reagent for the elimination of IL-2 receptor-positive cells. These experiments thus provide the scientific basis for use of alpha-particle-emitting radionuclides in immunotherapy

  1. Gene therapy of cancer and development of therapeutic target gene

    International Nuclear Information System (INIS)

    We applied HSV-tk/GCV strategy to orthotopic rat hepatoma model and showed anticancer effects of hepatoma. The increased expression of Lac Z gene after adenovirus-mediated gene delivery throughout hepatic artery was thought that is increased the possibility of gene therapy for curing hepatoma. With the construction of kGLP-laboratory, it is possible to produce a good quantity and quality of adenovirus in lage-scale production and purification of adenovirus vector. Also, the analysis of hepatoma related genes by PCR-LOH could be used for the diagnosis of patients and the development of therapeutic gene

  2. Gene therapy of cancer and development of therapeutic target gene

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Chang Min; Kwon, Hee Chung

    1998-04-01

    We applied HSV-tk/GCV strategy to orthotopic rat hepatoma model and showed anticancer effects of hepatoma. The increased expression of Lac Z gene after adenovirus-mediated gene delivery throughout hepatic artery was thought that is increased the possibility of gene therapy for curing hepatoma. With the construction of kGLP-laboratory, it is possible to produce a good quantity and quality of adenovirus in lage-scale production and purification of adenovirus vector. Also, the analysis of hepatoma related genes by PCR-LOH could be used for the diagnosis of patients and the development of therapeutic gene.

  3. Predictive factors for the development of persistent pain after breast cancer surgery

    DEFF Research Database (Denmark)

    Andersen, Kenneth Geving; Duriaud, Helle Molter; Jensen, Helle Elisabeth; Kroman, Niels; Kehlet, Henrik

    2015-01-01

    , and 1 year after surgery. A comprehensive validated questionnaire was used. Handling of the intercostobrachial nerve was registered by the surgeon. Factors known by the first 3 weeks after surgery were modeled in ordinal logistic regression analyses. Five hundred thirty-seven patients with baseline......Previous studies have reported that 15% to 25% of patients treated for breast cancer experience long-term moderate-to-severe pain in the area of surgery, potentially lasting for several years. Few prospective studies have included all potential risk factors for the development of persistent pain...... after breast cancer surgery (PPBCS). The aim of this prospective cohort study was to comprehensively identify factors predicting PPBCS. Patients scheduled for primary breast cancer surgery were recruited. Assessments were conducted preoperatively, the first 3 days postoperatively, and 1 week, 6 months...

  4. Mechanisms of autophagy and apoptosis:Recent developments in breast cancer cells

    Institute of Scientific and Technical Information of China (English)

    Juan; M; Esteve; Erwin; Knecht

    2011-01-01

    Autophagy,the pathway whereby cell components are degraded by lysosomes,is involved in the cell response to environmental stresses,such as nutrient deprivation,hypoxia or exposition to chemotherapeutic agents.Under these conditions,which are reminiscent of certain phases of tumor development,autophagy either promotes cell survival or induces cell death. This strengthens the possibility that autophagy could be an important target in cancer therapy,as has been proposed.Here,we describe the regulation of survival and death by autophagy and apoptosis,especially in cultured breast cancer cells.In particular,we discuss whether autophagy represents an apoptosis-independent process and/or if they share common pathways. We believe that understanding in detail the molecular mechanisms that underlie the relationships between autophagy and apoptosis in breast cancer cells could improve the available treatments for this disease.

  5. A multi-institute case-control study on the risk factors of developing pancreatic cancer.

    Science.gov (United States)

    Mizuno, S; Watanabe, S; Nakamura, K; Omata, M; Oguchi, H; Ohashi, K; Ohyanagi, H; Fujiki, T; Motojima, K

    1992-08-01

    A multi-institute, hospital-based, case-control study on pancreatic cancer was carried out to examine its association with preceding diseases, cigarette smoking, alcohol drinking and dietary factors. Analyses were based on 124 newly diagnosed exocrine pancreatic cancer cases and sex-, age- and institute-matched hospital controls in seven hospitals in Japan. Cigarette smoking showed a positive association with the risk of developing pancreatic cancer. Especially among smokers, a risk enhancing effect of involuntary/passive smoking prior to twenty years of age was observed (P tea or alcohol consumption. Among dietary factors, favoring food of a salty taste and drinking green tea five cups per day or more were positively associated with the risk. Drinking milk and eating fish everyday were inversely associated with the risk. PMID:1434027

  6. Development of botanical principles for clinical use in cancer: Where are we lacking?

    Directory of Open Access Journals (Sweden)

    R J Poojari

    2012-01-01

    Full Text Available Development of drugs from plant sources (botanicals for the treatment of cancer has not been successful in India, despite a plethora of medicinal plants and an equal number of experiments demonstrating anti-cancer activity of plant principles in vitro. There are several pitfalls in our approach to botanical drug development. Foremost is the lack of industry-academia collaborations in this field. Research goals in Indian academic institutions are generally short-term and mostly aimed at fulfilling the minimum requirements of a doctoral/MD or MPharm thesis. Secondly, quality assurance of herbal formulations is difficult to achieve and good manufacturing practices are expensive to implement. This could introduce bias during the biological evaluation of botanicals. A systematic approach covering a wide range of investigations including but not limited to mechanistic studies, potential herb-drug interactions, pharmacokinetics and bioavailability could help in the optimization of herbal formulations in the preclinical stage of development before they can be considered for clinical trials. Government initiatives such as Ayurveda, Unani, Siddha and Homeopathic have encouraged research in these areas, but are insufficient to promote focused and aggressive evaluation of potential herbs. Particular emphasis should be given to clinical pharmacokinetics, drug interactions and clinical trials in specific cancers for the evaluation of dosage, safety, efficacy and concomitant use with chemotherapy. Only such policies can result in meaningful evaluation of botanicals for cancer therapy.

  7. Fighting lung cancer in the developed world - a model of care in a UK hospital

    International Nuclear Information System (INIS)

    To highlight the initial management approach for Lung Cancer in a UK Hospital with the aim of translating the principles of such methodology to a developing country, such as Pakistan. A descriptive observational study was carried out at Stobhill Hospital , Glasgow, UK. The investigator (IMB) observed the Lung Cancer Service, attending the weekly 'New patients Clinic', 'Results Clinic', and 'Multidisciplinary team (MDT) meetings'. The process observations and the factual data describing the details of the service were recorded on a pre designed proforma. Observations relating to two aspects of this service (Results Clinic and MDT) are included in this report. The methodology of communicating results of lung cancer investigations to patients in a pre-planned and staged manner at a dedicated 'Results Clinic' was identified as a useful approach. A format of communication was consistently followed. The MDT consisted of a Respiratory Physician, Clinical Oncologist, Thoracic Surgeon, Radiologist, Pathologist and Palliative Care Specialist. Each patient's case was discussed on an individual basis and the team developed a consensus regarding diagnosis, staging of the disease, further need for diagnostic procedures and treatment options, bearing in mind the patient's performance status, co-morbidity and their wishes. This approach has improved the initial part of the lung cancer patient journey and components of this approach could easily be transferred to a developing country (JPMA 60:93; 2010). (author)

  8. Modifications in Dynamic Contrast-Enhanced Magnetic Resonance Imaging Parameters After α-Particle-Emitting {sup 227}Th-trastuzumab Therapy of HER2-Expressing Ovarian Cancer Xenografts

    Energy Technology Data Exchange (ETDEWEB)

    Heyerdahl, Helen, E-mail: Helen.Heyerdahl@rr-research.no [Department of Radiation Biology, Institute for Cancer Research, Oslo University Hospital - The Norwegian Radium Hospital, Oslo (Norway); Røe, Kathrine [Department of Oncology, Division of Medicine, Akershus University Hospital, Lørenskog (Norway); Brevik, Ellen Mengshoel [Department of Research and Development, Algeta ASA, Oslo (Norway); Dahle, Jostein [Nordic Nanovector AS, Oslo (Norway)

    2013-09-01

    Purpose: The purpose of this study was to investigate the effect of α-particle-emitting {sup 227}Th-trastuzumab radioimmunotherapy on tumor vasculature to increase the knowledge about the mechanisms of action of {sup 227}Th-trastuzumab. Methods and Materials: Human HER2-expressing SKOV-3 ovarian cancer xenografts were grown bilaterally in athymic nude mice. Mice with tumor volumes 253 ± 36 mm{sup 3} (mean ± SEM) were treated with a single injection of either {sup 227}Th-trastuzumab at a dose of 1000 kBq/kg body weight (treated group, n=14 tumors) or 0.9% NaCl (control group, n=10 tumors). Dynamic T1-weighted contrast-enhanced magnetic resonance imaging (DCEMRI) was used to study the effect of {sup 227}Th-trastuzumab on tumor vasculature. DCEMRI was performed before treatment and 1, 2, and 3 weeks after therapy. Tumor contrast-enhancement curves were extracted voxel by voxel and fitted to the Brix pharmacokinetic model. Pharmacokinetic parameters for the tumors that underwent radioimmunotherapy were compared with the corresponding parameters of control tumors. Results: Significant increases of k{sub ep}, the rate constant of diffusion from the extravascular extracellular space to the plasma (P<.05), and k{sub el,} the rate of clearance of contrast agent from the plasma (P<.01), were seen in the radioimmunotherapy group 2 and 3 weeks after injection, compared with the control group. The product of k{sub ep} and the amplitude parameter A, associated with increased vessel permeability and perfusion, was also significantly increased in the radioimmunotherapy group 2 and 3 weeks after injection (P<.01). Conclusions: Pharmacokinetic modeling of MRI contrast-enhancement curves evidenced significant alterations in parameters associated with increased tumor vessel permeability and tumor perfusion after {sup 227}Th-trastuzumab treatment of HER2-expressing ovarian cancer xenografts.

  9. Prevalence and risk factors for development of lymphedema following breast cancer treatment

    OpenAIRE

    Deo S; Ray S; Rath G; Shukla N; Kar M; Asthana S; Raina V

    2004-01-01

    BACKGROUND : Early detection and multimodality therapy has resulted in an overall improvement of survival among breast cancer patients. Despite a significant shift in the treatment approach from radical mastectomy to breast conservation a significant number of patients develop lymphedema. This study was conducted to evaluate the prevalence and risk factors for development of lymphedema. SETTINGS AND DESIGN : Retrospective analysis for prevalence of lymphedema in a tertiary care regional cance...

  10. Development of Foot Massage Program on Nausea and Vomiting for Cancer Patients: A Literature Review

    OpenAIRE

    Ni Ketut Guru Prapti; Wongchan Petpichetchian; Wimonrat Chongcharoen

    2012-01-01

    Objective: This study aims to develop a foot massage program to support care activity in reducing nausea and vomiting for cancer patients undergoing chemotherapy. Two phases, a literature review and the development of a foot massage program were conducted. The literature review was to analyze state of the art massage techniques by reviewing problems, related theories and supporting evidence. Method: Eight published studies in the English language were reviewed. A massage can be performed for ...

  11. Clinical trial designs for rare diseases: Studies developed and discussed by the International Rare Cancers Initiative

    Science.gov (United States)

    Bogaerts, Jan; Sydes, Matthew R.; Keat, Nicola; McConnell, Andrea; Benson, Al; Ho, Alan; Roth, Arnaud; Fortpied, Catherine; Eng, Cathy; Peckitt, Clare; Coens, Corneel; Pettaway, Curtis; Arnold, Dirk; Hall, Emma; Marshall, Ernie; Sclafani, Francesco; Hatcher, Helen; Earl, Helena; Ray-Coquard, Isabelle; Paul, James; Blay, Jean-Yves; Whelan, Jeremy; Panageas, Kathy; Wheatley, Keith; Harrington, Kevin; Licitra, Lisa; Billingham, Lucinda; Hensley, Martee; McCabe, Martin; Patel, Poulam M.; Carvajal, Richard; Wilson, Richard; Glynne-Jones, Rob; McWilliams, Rob; Leyvraz, Serge; Rao, Sheela; Nicholson, Steve; Filiaci, Virginia; Negrouk, Anastassia; Lacombe, Denis; Dupont, Elisabeth; Pauporté, Iris; Welch, John J.; Law, Kate; Trimble, Ted; Seymour, Matthew

    2015-01-01

    Background The past three decades have seen rapid improvements in the diagnosis and treatment of most cancers and the most important contributor has been research. Progress in rare cancers has been slower, not least because of the challenges of undertaking research. Settings The International Rare Cancers Initiative (IRCI) is a partnership which aims to stimulate and facilitate the development of international clinical trials for patients with rare cancers. It is focused on interventional – usually randomised – clinical trials with the clear goal of improving outcomes for patients. The key challenges are organisational and methodological. A multi-disciplinary workshop to review the methods used in ICRI portfolio trials was held in Amsterdam in September 2013. Other as-yet unrealised methods were also discussed. Results The IRCI trials are each presented to exemplify possible approaches to designing credible trials in rare cancers. Researchers may consider these for use in future trials and understand the choices made for each design. Interpretation Trials can be designed using a wide array of possibilities. There is no ‘one size fits all’ solution. In order to make progress in the rare diseases, decisions to change practice will have to be based on less direct evidence from clinical trials than in more common diseases. PMID:25542058

  12. In memoriam: an appreciation for the NCI R25T cancer education and career development program.

    Science.gov (United States)

    Chang, Shine

    2014-06-01

    On September 7, 2013, the NCI R25T award mechanism ended its final "receipt/review/award cycle" after more than two decades shaping the cancer prevention and control workforce. Created in 1991 to respond to a national shortage of cancer prevention and control researchers, the R25T supported innovative institutional programs with specialized curricula preparing individuals for careers as independent scientists for the field. Required elements ensured developing transdisciplinary sensibilities and skills highly suited to team science, including conducting collaborative research with mentors of complementary expertise. R25Ts provided trainee stipends, research, education, and travel funds at levels far higher than T32 National Service Research Awards to attract individuals from diverse disciplines. Graduates are faculty at all academic ranks, and hold leadership positions such as associate directors of cancer prevention and control. Beyond its trainees, R25Ts also recruited into the field other students exposed through courses in specialized prevention curricula, as well as course instructors and trainee mentors, who did not initially consider their work to be relevant to cancer prevention. Although advances are being achieved, prevention efforts are not yet fully realized, and currently unknown is the impact on the workforce of terminating the R25T, including whether it is another barrier to preventing cancer. PMID:24895444

  13. Irregular menses predicts ovarian cancer: Prospective evidence from the Child Health and Development Studies.

    Science.gov (United States)

    Cirillo, Piera M; Wang, Erica T; Cedars, Marcelle I; Chen, Lee-May; Cohn, Barbara A

    2016-09-01

    We tested the hypothesis that irregular menstruation predicts lower risk for ovarian cancer, possibly due to less frequent ovulation. We conducted a 50-year prospective study of 15,528 mothers in the Child Health and Development Studies cohort recruited from the Kaiser Foundation Health Plan from 1959 to 1966. Irregular menstruation was classified via medical record and self-report at age 26. We identified 116 cases and 84 deaths due to ovarian cancer through 2011 via linkage to the California Cancer Registry and Vital Statistics. Contrary to expectation, women with irregular menstrual cycles had a higher risk of ovarian cancer incidence and mortality over the 50-year follow-up. Associations increased with age (p age 70 (95% confidence interval [CI] = 1.1, 3.4) rising to a 3-fold increase by age 77 (95% CI = 1.5, 6.7 for incidence; 95% CI = 1.4, 5.9 for mortality). We also found a 3-fold higher risk of mortality for high-grade serous tumors (95% CI = 1.3, 7.6) that did not vary by age. This is the first prospective study to show an association between irregular menstruation and ovarian cancer-we unexpectedly found higher risk for women with irregular cycles. These women are easy to identify and many may have polycystic ovarian syndrome. Classifying high-risk phenotypes such as irregular menstruation creates opportunities to find novel early biomarkers, refine clinical screening protocols and potentially develop new risk reduction strategies. These efforts can lead to earlier detection and better survival for ovarian cancer. PMID:27082375

  14. Review of 90Y-ibritumomab tiuxetan as first-line consolidation radio-immunotherapy for B-cell follicular non-Hodgkin’s lymphoma

    International Nuclear Information System (INIS)

    Several studies have indicated that radioimmunotherapy is an effective and clinically relevant complementary therapeutic approach for patients with B-cell non-Hodgkin’s lymphoma (NHL) and may convert partial to complete response when given as consolidation after induction chemotherapy. Yttrium-90(90Y)-ibritumomab tiuxetan (90Y-IT, Zevalin®, Y2B8) has documented efficacy for both indolent and aggressive NHL. Patients considered eligible for 90Y-IT treatment should satisfy several screening criteria. A recently completed randomized study for patients with follicular lymphoma has demonstrated that 90Y-ibritumomab consolidation also produced a marked prolongation of the median time to progression from 13.5 to 37 months, while partial responders seem to derive relatively more benefit. Other published and ongoing studies explore a similar use for patients with aggressive lymphoma. Studies are comparing the use of 90Y-IT consolidation with the anti-CD20 antibody rituximab maintenance, which is also gaining acceptance. In conclusion, the documented benefit of radioimmunotherapy should be viewed in the context of the goals of treatment and the changing standards of care for lymphoma

  15. Telomerase as a Cancer Target. Development of New Molecules.

    Science.gov (United States)

    Gomez, D L Mengual; Armando, R G; Cerrudo, C S; Ghiringhelli, P D; Gomez, D E

    2016-01-01

    Telomeres are the terminal part of the chromosome containing a long repetitive and noncodifying sequence that has as function protecting the chromosomes. In normal cells, telomeres lost part of such repetitive sequence in each mitosis, until telomeres reach a critical point, triggering at that time senescence and cell death. However, in most of tumor cells in each cell division a part of the telomere is lost, however the appearance of an enzyme called telomerase synthetize the segment that just has been lost, therefore conferring to tumor cells the immortality hallmark. Telomerase is significantly overexpressed in 80-95% of all malignant tumors, being present at low levels in few normal cells, mostly stem cells. Due to these characteristics, telomerase has become an attractive target for new and more effective anticancer agents. The capability of inhibiting telomerase in tumor cells should lead to telomere shortening, senescence and apoptosis. In this work, we analyze the different strategies for telomerase inhibition, either in development, preclinical or clinical stages taking into account their strong points and their caveats. We covered strategies such as nucleosides analogs, oligonucleotides, small molecule inhibitors, G-quadruplex stabilizers, immunotherapy, gene therapy, molecules that affect the telomere/ telomerase associated proteins, agents from microbial sources, among others, providing a balanced evaluation of the status of the inhibitors of this powerful target together with an analysis of the challenges ahead. PMID:26873194

  16. Telomerase as a Cancer Target. Development of New Molecules

    Science.gov (United States)

    Gomez, D.L. Mengual; Armando, R.G.; Cerrudo, C.S.; Ghiringhelli, P.D.; Gomez, D.E.

    2016-01-01

    Telomeres are the terminal part of the chromosome containing a long repetitive and non-codifying sequence that has as function protecting the chromosomes. In normal cells, telomeres lost part of such repetitive sequence in each mitosis, until telomeres reach a critical point, triggering at that time senescence and cell death. However, in most of tumor cells in each cell division a part of the telomere is lost, however the appearance of an enzyme called telomerase synthetize the segment that just has been lost, therefore conferring to tumor cells the immortality hallmark. Telomerase is significantly overexpressed in 80–95% of all malignant tumors, being present at low levels in few normal cells, mostly stem cells. Due to these characteristics, telomerase has become an attractive target for new and more effective anticancer agents. The capability of inhibiting telomerase in tumor cells should lead to telomere shortening, senescence and apoptosis. In this work, we analyze the different strategies for telomerase inhibition, either in development, preclinical or clinical stages taking into account their strong points and their caveats. We covered strategies such as nucleosides analogs, oligonucleotides, small molecule inhibitors, G-quadruplex stabilizers, immunotherapy, gene therapy, molecules that affect the telomere/telomerase associated proteins, agents from microbial sources, among others, providing a balanced evaluation of the status of the inhibitors of this powerful target together with an analysis of the challenges ahead. PMID:26873194

  17. Engaging African Americans in developing an intervention to reduce breast cancer recurrence: A brief report

    Science.gov (United States)

    Smith, Selina A.; Whitehead, Mary S.; Sheats, Joyce Q.; Fontenot, Brittney; Alema-Mensah, Ernest; Ansa, Benjamin

    2016-01-01

    Background To develop a culturally appropriate lifestyle intervention, involvement of its intended users is needed. Methods Members of an African American (AA) breast cancer support group participated in two 4-hour guided discussions, which were audiotaped, transcribed, and analyzed to guide the content. Results The support group collaborated with researchers to develop 24 experiential nutrition education sessions using a social cognitive framework and incorporating self-regulation skills (goal-setting, self-monitoring, problem-solving, stimulus control) and social support to enhance self-efficacy for changes in dietary intake. Conclusions Community engagement fostered autonomy, built collaboration, and enhanced the capacity of AA breast cancer survivors to participate in developing a lifestyle intervention.

  18. Detection of Prostate Cancer: Quantitative Multiparametric MR Imaging Models Developed Using Registered Correlative Histopathology.

    Science.gov (United States)

    Metzger, Gregory J; Kalavagunta, Chaitanya; Spilseth, Benjamin; Bolan, Patrick J; Li, Xiufeng; Hutter, Diane; Nam, Jung W; Johnson, Andrew D; Henriksen, Jonathan C; Moench, Laura; Konety, Badrinath; Warlick, Christopher A; Schmechel, Stephen C; Koopmeiners, Joseph S

    2016-06-01

    Purpose To develop multiparametric magnetic resonance (MR) imaging models to generate a quantitative, user-independent, voxel-wise composite biomarker score (CBS) for detection of prostate cancer by using coregistered correlative histopathologic results, and to compare performance of CBS-based detection with that of single quantitative MR imaging parameters. Materials and Methods Institutional review board approval and informed consent were obtained. Patients with a diagnosis of prostate cancer underwent multiparametric MR imaging before surgery for treatment. All MR imaging voxels in the prostate were classified as cancer or noncancer on the basis of coregistered histopathologic data. Predictive models were developed by using more than one quantitative MR imaging parameter to generate CBS maps. Model development and evaluation of quantitative MR imaging parameters and CBS were performed separately for the peripheral zone and the whole gland. Model accuracy was evaluated by using the area under the receiver operating characteristic curve (AUC), and confidence intervals were calculated with the bootstrap procedure. The improvement in classification accuracy was evaluated by comparing the AUC for the multiparametric model and the single best-performing quantitative MR imaging parameter at the individual level and in aggregate. Results Quantitative T2, apparent diffusion coefficient (ADC), volume transfer constant (K(trans)), reflux rate constant (kep), and area under the gadolinium concentration curve at 90 seconds (AUGC90) were significantly different between cancer and noncancer voxels (P < .001), with ADC showing the best accuracy (peripheral zone AUC, 0.82; whole gland AUC, 0.74). Four-parameter models demonstrated the best performance in both the peripheral zone (AUC, 0.85; P = .010 vs ADC alone) and whole gland (AUC, 0.77; P = .043 vs ADC alone). Individual-level analysis showed statistically significant improvement in AUC in 82% (23 of 28) and 71% (24 of 34

  19. Radioimmunotherapy for first-line and relapse treatment of aggressive B-cell non-Hodgkin lymphoma: an analysis of 215 patients registered in the international RIT-Network

    International Nuclear Information System (INIS)

    Very few reliable clinical data about the use of radioimmunotherapy in aggressive B-cell lymphoma exist. Patients with aggressive B-cell lymphoma registered in the international RIT-Network were analysed with regard to prior treatment, response and side effects. The RIT-Network is a web-based registry that collects observational data from radioimmunotherapy-treated patients with malignant lymphoma across 13 countries. This analysis included 215 with aggressive B-cell lymphoma out of 232 patients registered in the RIT-Network. Histological subtypes were as follows: 190 diffuse large B-cell, 15 primary mediastinal, 9 anaplastic large cell, and 1 intravascular lymphoma. The median age of the patients was 62 years (range 17 - 88), with 27 % above the age of 70 years. Radioimmunotherapy was mainly used as consolidation after first-line or second-line chemotherapy (56.1 %), as part of third-line to eighth-line therapy for relapse (16.4 %), and in refractory disease (12.2 %). Grade IV neutropenia and thrombopenia and grade III anaemia were observed. The median time to recovery of blood count was 81 days (range 0 - 600 days). The overall response rate was 63.3 %. The complete response rate was 76.4 % in patients treated as part of first-line therapy, and 44.3 % in patients with relapse. Mean overall survival in first-line therapy patients was 32.7 months and 14.0 months in patients with relapse or refractory disease, respectively. Most patients with aggressive B-cell lymphoma in the RIT-Network received radioimmunotherapy as consolidation after first-line therapy with excellent complete remission and overall survival rates compared to published data. In relapsed aggressive B-cell lymphoma, radioimmunotherapy is a safe and feasible treatment leading to satisfactory response rates with acceptable toxicity. (orig.)

  20. Radioimmunotherapy for first-line and relapse treatment of aggressive B-cell non-Hodgkin lymphoma: an analysis of 215 patients registered in the international RIT-Network

    Energy Technology Data Exchange (ETDEWEB)

    Hohloch, Karin; Lankeit, H.K.; Truemper, L. [Georg August University, Hematology and Oncology, Goettingen (Germany); Zinzani, P.L. [University of Bologna, Institute of Hematology and Medical Oncology ' ' L. e A. Seragnoli' ' , Bologna (Italy); Scholz, C.W. [Charite, University Berlin, Hematology, Oncology and Tumor Immunology, Berlin (Germany); Lorsbach, M.; Windemuth-Kieselbach, C. [Alcedis GmbH, Giessen (Germany)

    2014-08-15

    Very few reliable clinical data about the use of radioimmunotherapy in aggressive B-cell lymphoma exist. Patients with aggressive B-cell lymphoma registered in the international RIT-Network were analysed with regard to prior treatment, response and side effects. The RIT-Network is a web-based registry that collects observational data from radioimmunotherapy-treated patients with malignant lymphoma across 13 countries. This analysis included 215 with aggressive B-cell lymphoma out of 232 patients registered in the RIT-Network. Histological subtypes were as follows: 190 diffuse large B-cell, 15 primary mediastinal, 9 anaplastic large cell, and 1 intravascular lymphoma. The median age of the patients was 62 years (range 17 - 88), with 27 % above the age of 70 years. Radioimmunotherapy was mainly used as consolidation after first-line or second-line chemotherapy (56.1 %), as part of third-line to eighth-line therapy for relapse (16.4 %), and in refractory disease (12.2 %). Grade IV neutropenia and thrombopenia and grade III anaemia were observed. The median time to recovery of blood count was 81 days (range 0 - 600 days). The overall response rate was 63.3 %. The complete response rate was 76.4 % in patients treated as part of first-line therapy, and 44.3 % in patients with relapse. Mean overall survival in first-line therapy patients was 32.7 months and 14.0 months in patients with relapse or refractory disease, respectively. Most patients with aggressive B-cell lymphoma in the RIT-Network received radioimmunotherapy as consolidation after first-line therapy with excellent complete remission and overall survival rates compared to published data. In relapsed aggressive B-cell lymphoma, radioimmunotherapy is a safe and feasible treatment leading to satisfactory response rates with acceptable toxicity. (orig.)