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107 results on '"TUMOR XENOGRAFTS"'

101. Examination of Potential Anti-Tumor Activity of N-Thiolated b-Lactam Antibiotics in Nude Mice Bearing Human Breast Tumors

Author

WAYNE STATE UNIV DETROIT MI, Dou, Q. P., WAYNE STATE UNIV DETROIT MI, and Dou, Q. P.

Abstract

Activation of the cellular apoptotic program is a current strategy for the prevention and treatment of human cancer including breast cancer. Because of the ease of synthesis and structural manipulation, small molecules with apoptosis-inducing ability have great potential to be developed into chemotherapeutic drugs. The beta-lactam antibiotics have for the past 60 years played an essential role in treating bacterial infections without causing toxic side effects in the host. We hypothesized that active N-thiolated beta-lactams can damage DNA and induce apoptosis in human breast cancer cells in nude mice. In this final report. we have first evaluated potencies of many novel synthetic beta-lactams to inhibit proliferation and induce apoptosis in human cancer cell. We then determined whether several of these beta-lactam, L1, HY2, HY14, HY15 and SC4, could damage breast tumor cell DNA and inhibit breast tumor growth in vivo. We have found that these beta-lactams inhibited growth of implanted MDA-MB-231 breast tumors in a concentration-dependent manner, associated with their DNA-damaging activities. Our studies have provided strong support for proof-of-concept of the potential use of these N-thiolated beta-lactams in breast cancer prevention and treatment.

Published
2006

102. Examination pf Potential Anti-Tumor Activity of N-Thiolated B-Lactam Antibiotics in Nude Mice Bearing Human Breast Tumors

Author

WAYNE STATE UNIV DETROIT MI, Dou, Q. P., WAYNE STATE UNIV DETROIT MI, and Dou, Q. P.

Abstract

Activation of the cellular apoptotic program is a current strategy for the prevention and treatment of human cancer including breast cancer. Because of the ease of synthesis and structural manipulation, small molecules with apoptosis-inducing ability have great potential to be developed into chemotherapeutic drugs. The beta-lactam antibiotics have for the past 60 years played an essential role in treating bacterial infections without causing toxic side effects in the host. We hypothesized that active N-thiolated b-lactams can damage DNA and induce apoptosis in human breast cancer cells in nude mice. In this summary report, we have first evaluated potencies of several novel synthetic beta-lactams to inhibit proliferation and induce apoptosis in human cancer cells. We then determined whether one of these b-lactams, HY14, could inhibit breast tumor growth in vivo. We have found that HY14 inhibited growth of implanted MDA-MB-231 breast tumors in a concentrationdependent manner, associated with its DNA-damaging activity. We are currently testing more novel beta-lactams in nude mice bearing human breast tumors. Our studies have provided strong support for proof-of-concept of the potential use of these Nthiolated beta-lactams in breast cancer prevention and treatment., The original document contains color images.

Published
2005

103. Driving p53 response to Bax activation greatly enhances sensitivity to taxol by inducing massive apoptosis

Author

Tatiana Mincioni, Sara Vignati, Raffaella Giavazzi, Massimo Broggini, Paola De Feudis, Cosmo Rossi, and Maurizio D'Incalci

Subjects
p53, Cancer Research, endocrine system diseases, Paclitaxel, Brief Article, Transplantation, Heterologous, tumor xenografts, Mice, Nude, Apoptosis, lcsh:RC254-282, anticancer agents, chemistry.chemical_compound, Mice, Bcl-2-associated X protein, In vivo, Proto-Oncogene Proteins, Tumor Cells, Cultured, Animals, Humans, bcl-2-Associated X Protein, biology, lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens, Antineoplastic Agents, Phytogenic, In vitro, Transplantation, chemistry, Proto-Oncogene Proteins c-bcl-2, Cell culture, biology.protein, Cancer research, Female, Tumor Suppressor Protein p53, transcription, Neoplasm Transplantation, P53 binding
Abstract

The proapoptotic gene bax is one of the downstream effectors of p53. The p53 binding site in the bax promoter is less responsive to p53 than the one in the growth arrest mediating gene p21. We introduced the bax gene under the control of 13 copies of a strong p53 responsive element into two ovarian cancer cell lines. The clones expressing bax under the control of p53 obtained from the wild-type (wt) p53-expressing cell line A2780 were much more sensitive (500- to 1000-fold) to the anticancer agent taxol than the parent cell line, with a higher percentage of cells undergoing apoptosis after drug treatment that was clearly p53-dependent and bax-mediated. Xenografts established in nude mice from one selected clone (A2780/C3) were more responsive to taxol than the parental line and the apoptotic response of A2780/C3 tumors was also increased after treatment. Introduction of the same plasmid into the p53 null SKOV3 cell line did not alter the sensitivity to taxol or the induction of apoptosis. In conclusion, driving the p53 response (after taxol treatment) by activating the bax gene rather than the p21 gene results in induction of massive apoptosis, in vitro and in vivo, and greatly enhances sensitivity to the drug.

Published
2000

104. Experimental evaluation of functional imaging for radiotherapy.

Author

Zips, Daniel, Yaromina, Ala, Schütze, Christina, Wüllrich, Katharina, Krause, Marie, Krause, Mechthild, Hessel, Franziska, Eicheler, Wolfgang, Dörfler, Annegret, Brüchner, Kerstin, Menegakis, Apostolos, Xuanjing Zhou, Bergmann, Ralf, Hoff, Jörg, Beuthien-Baumann, Bettina, Baumann, Michael, Schütze, Christina, Wüllrich, Katharina, Dörfler, Annegret, and Brüchner, Kerstin

Subjects
MEDICAL research, MEDICAL radiology, RADIOTHERAPY, HYPOXEMIA, CELL proliferation, LABORATORY mice
Abstract

The article provides information on several studies that evaluate the functional imaging for radiotherapy. These research used xenotransplanted tumors in nude mice which were carried out in laboratories. Meanwhile, the researchers also used local tumor control after single dose irradiation and uptake with proliferation and hypoxia determined by functional histology.

Published
2007
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105. ER maleate is a novel anticancer agent in oral cancer: implications for cancer therapy.

Author

Fu G, Somasundaram RT, Jessa F, Srivastava G, MacMillan C, Witterick I, Walfish PG, and Ralhan R

Subjects
Adult, Aged, Aged, 80 and over, Animals, Apoptosis drug effects, Carcinoma, Squamous Cell enzymology, Carcinoma, Squamous Cell mortality, Cell Cycle Proteins biosynthesis, Cell Movement drug effects, Cell Proliferation drug effects, Female, Head and Neck Neoplasms enzymology, Head and Neck Neoplasms mortality, Humans, Kaplan-Meier Estimate, Male, Mice, Mice, Inbred NOD, Mice, SCID, Middle Aged, Mouth Neoplasms enzymology, Mouth Neoplasms mortality, Protein Kinase Inhibitors pharmacology, Protein Serine-Threonine Kinases biosynthesis, Proto-Oncogene Proteins biosynthesis, Squamous Cell Carcinoma of Head and Neck, Syk Kinase biosynthesis, Xenograft Model Antitumor Assays, Polo-Like Kinase 1, Antineoplastic Agents pharmacology, Carcinoma, Squamous Cell drug therapy, Cell Cycle Proteins antagonists & inhibitors, Head and Neck Neoplasms drug therapy, Mouth Neoplasms drug therapy, Protein Serine-Threonine Kinases antagonists & inhibitors, Proto-Oncogene Proteins antagonists & inhibitors, Syk Kinase antagonists & inhibitors
Abstract

ER maleate [10-(3-Aminopropyl)-3, 4-dimethyl-9(10H)-acridinone maleate] identified in a kinome screen was investigated as a novel anticancer agent for oral squamous cell carcinoma (OSCC). Our aim was to demonstrate its anticancer effects, identify putative molecular targets and determine their clinical relevance and investigate its chemosensitization potential for platinum drugs to aid in OSCC management. Biologic effects of ER maleate were determined using oral cancer cell lines in vitro and oral tumor xenografts in vivo. mRNA profiling, real time PCR and western blot revealed ER maleate modulated the expression of polo-like kinase 1 (PLK1) and spleen tyrosine kinase (Syk). Their clinical significance was determined in oral SCC patients by immunohistochemistry and correlated with prognosis by Kaplan-Meier survival and multivariate Cox regression analyses. ER maleate induced cell apoptosis, inhibited proliferation, colony formation, migration and invasion in oral cancer cells. Imagestream analysis revealed cell cycle arrest in G2/M phase and increased polyploidy, unravelling deregulation of cell division and cell death. Mechanistically, ER maleate decreased expression of PLK1 and Syk, induced cleavage of PARP, caspase9 and caspase3, and increased chemosensitivity to carboplatin; significantly suppressed tumor growth and increased antitumor activity of carboplatin in tumor xenografts. ER maleate treated tumor xenografts showed reduced PLK1 and Syk expression. Clinical investigations revealed overexpression of PLK1 and Syk in oral SCC patients that correlated with disease prognosis. Our in vitro and in vivo findings provide a strong rationale for pre-clinical efficacy of ER maleate as a novel anticancer agent and chemosensitizer of platinum drugs for OSCC.

Published
2016
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106. Uncovering Metabolic Effects of Anti-angiogenic Therapy in Tumors by Induced Metabolic Bioluminescence Imaging.

Author

Indraccolo S, Walenta S, and Mueller-Klieser W

Subjects
Angiogenesis Inhibitors pharmacology, Animals, Bevacizumab pharmacology, Cell Line, Tumor, Female, Glycolysis drug effects, Humans, Mice, Mice, SCID, Ovarian Neoplasms metabolism, Xenograft Model Antitumor Assays, Angiogenesis Inhibitors administration & dosage, Bevacizumab administration & dosage, Luminescent Measurements methods, Ovarian Neoplasms drug therapy
Abstract

Induced metabolic bioluminescence imaging (imBI) is an imaging technique which enables detection of various metabolites associated with glycolysis in tumor sections. Signals captured by imBI can be used to chart the topographic distribution of lactate, glucose, pyruvate, and ATP and quantify their absolute amount. ImBi can enable us to perform metabolic classification of tumors as well as to detect metabolic changes in the glycolytic pathway associated with certain therapies, such as anti-angiogenic drugs.

Published
2016
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107. 68Ga-Chloride PET Reveals Human Pancreatic Adenocarcinoma Xenografts in Rats—Comparison with FDG

Author

Tiina Ujula, Pertti Lehikoinen, Hannu Sipilä, Tapio Viljanen, Anne Roivainen, Anu Autio, Pirkko Härkönen, Tuula Tolvanen, Satu Salomäki, and Pauliina Luoto

Subjects
Cancer Research, Pathology, medicine.medical_specialty, Gallium, Gallium Radioisotopes, Chloride, 030218 nuclear medicine & medical imaging, 03 medical and health sciences, 0302 clinical medicine, Text mining, Tumor xenografts, Fluorodeoxyglucose F18, Cell Line, Tumor, medicine, Animals, Humans, Tissue Distribution, Radiology, Nuclear Medicine and imaging, Medicine(all), business.industry, Gallium-68, medicine.disease, Immunohistochemistry, Rats, 3. Good health, Pancreatic Neoplasms, PET, Oncology, Positron-Emission Tomography, 030220 oncology & carcinogenesis, Autoradiography, Adenocarcinoma, business, Nuclear medicine, Neoplasm Transplantation, Research Article, Fluorine-18 FDG, medicine.drug
Abstract

Purpose The aim of the study was to compare 68Ga-chloride with 2-[18F]fluoro-2-deoxy-d-glucose (FDG) for the imaging of pancreatic xenografts. Procedures Rats with subcutaneous human pancreatic adenocarcinoma xenografts were evaluated in vivo by dynamic positron emission tomography (PET) and ex vivo by measuring radioactivity of excised tissues and by digital autoradiography of tumor cryosections. Results Both tracers were capable of delineating all subcutaneous tumors from surrounding tissues by PET. The standardized uptake values of tumors by PET were 0.9 ± 0.3 (mean ± SD) for 68Ga-chloride (n = 13) and 1.8 ± 1.2 for FDG (n = 11). Ex vivo studies showed tumor-to-muscle ratio of 4.0 ± 0.3 for 68Ga-chloride (n = 4) and 7.9 ± 3.2 for FDG (n = 4). Conclusions 68Ga-chloride delineated subcutaneously implanted pancreatic adenocarcinoma xenografts by PET, but the uptake was lower than FDG. Further studies to clarify the value of 68Ga-chloride for PET imaging of tumors are warranted.

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