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1. Kamuhabwa AA, Roskams T, D'Hallewin MA, Baert L, Van Poppel H, de Witte PA: Whole bladder wall photodynamic therapy of transitional cell carcinoma rat bladder tumors using intravesically administered hypericin. Int J Cancer; 2003 Nov 10;107(3):460-7
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  • [Title] Whole bladder wall photodynamic therapy of transitional cell carcinoma rat bladder tumors using intravesically administered hypericin.
  • Whole-bladder wall photodynamic therapy (PDT) is a promising treatment for carcinoma in situ (CIS) and diffuse premalignant changes of the bladder.
  • After the results of our clinical studies showing that intravesical hypericin selectively accumulates in superficial bladder tumors, we investigated the hypericin-PDT efficacy in an AY-27 orthotopic transitional cell carcinoma rat bladder tumor model.
  • After the instillation of hypericin (30 microM, 2 hr) in the bladder, tumors were irradiated (25-50 mW/cm 6-48 J/cm(2)) using 595 nm laser light.
  • Histological assessment of bladder sections 2 days after PDT showed tumor destruction, with tumor cells shrinking and detaching from the bladder wall.
  • There were tumor regrowth 1-3 weeks after treatment.
  • The in vivo/in vitro clonogenic assay results revealed up to 98% of tumor cell kill by hypericin PDT.
  • A small percentage (2-5%) of tumor cells that survive the photodynamic treatment resulting in tumor regrowth after a prolonged period of time is likely due to oxygen depletion during light irradiation.
  • [MeSH-major] Carcinoma, Transitional Cell / drug therapy. Perylene / administration & dosage. Perylene / analogs & derivatives. Photochemotherapy. Urinary Bladder Neoplasms / drug therapy

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  • [Copyright] Copyright 2003 Wiley-Liss, Inc.
  • (PMID = 14506748.001).
  • [ISSN] 0020-7136
  • [Journal-full-title] International journal of cancer
  • [ISO-abbreviation] Int. J. Cancer
  • [Language] eng
  • [Publication-type] Journal Article; Research Support, Non-U.S. Gov't
  • [Publication-country] United States
  • [Chemical-registry-number] 5QD5427UN7 / Perylene; 7V2F1075HD / hypericin
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2. Estrada CR, Salanga M, Bielenberg DR, Harrell WB, Zurakowski D, Zhu X, Palmer MR, Freeman MR, Adam RM: Behavioral profiling of human transitional cell carcinoma ex vivo. Cancer Res; 2006 Mar 15;66(6):3078-86
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  • [Title] Behavioral profiling of human transitional cell carcinoma ex vivo.
  • Outcome studies of many types of cancer have revealed that tumors of indistinguishable histologic appearance may differ significantly in aggressiveness and in their response to therapy.
  • A strategy that would enable early identification of patients at high risk for disease progression and allow screening of multiple therapeutic agents simultaneously for efficacy would improve clinical management.
  • We have developed an orthotopic organ culture model of bladder cancer in which quantum dot-based fluorescent imaging approaches are used to obtain quantitative measurements of tumor cell behavior.
  • Human transitional cell carcinoma (TCC) cells are labeled with quantum dot nanoparticles, and the cells instilled into the rat bladder in vivo, after which the bladder is excised and cultured ex vivo.
  • Cell implantation, proliferation, and invasion into the organ wall are monitored using epifluorescence imaging and two-photon laser scanning confocal microscopy.
  • Using this approach, we were able to assign distinct phenotypes to two metastatic bladder cancer cell lines based on different patterns of invasiveness into the bladder wall.
  • We also showed that established tumor cell masses regressed following intravesical administration of the chemotherapeutic drug thiotepa.
  • [MeSH-major] Carcinoma, Transitional Cell / pathology. Urinary Bladder Neoplasms / pathology
  • [MeSH-minor] Animals. Cell Growth Processes / physiology. Female. Humans. Microscopy, Fluorescence. Neoplasm Invasiveness. Neoplasm Transplantation. Organ Culture Techniques / methods. Quantum Dots. Rats. Tumor Cells, Cultured

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  • (PMID = 16540657.001).
  • [ISSN] 0008-5472
  • [Journal-full-title] Cancer research
  • [ISO-abbreviation] Cancer Res.
  • [Language] eng
  • [Grant] United States / NIDDK NIH HHS / DK / P50 DK65298; United States / NIDDK NIH HHS / DK / R01 DK57691; United States / NIDDK NIH HHS / DK / R21 DK66412; United States / NIDDK NIH HHS / DK / R37 DK47556
  • [Publication-type] Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't
  • [Publication-country] United States
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3. Perabo FG, Demant AW, Wirger A, Schmidt DH, Sitia M, Wardelmann E, Müller SC, Kohn EC: Carboxyamido-triazole (CAI) reverses the balance between proliferation and apoptosis in a rat bladder cancer model. Anticancer Res; 2005 Mar-Apr;25(2A):725-9
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  • [Title] Carboxyamido-triazole (CAI) reverses the balance between proliferation and apoptosis in a rat bladder cancer model.
  • Carboxyamido-triazole (CAI) is an orally bioavailable calcium influx and signal transduction inhibitor that has been shown to be anti-invasive, anti-angiogenic and anti-metastatic in different human tumors including transitional cell carcinoma.
  • This study was undertaken to further evaluate the activity of CAI in a rat bladder cancer model.
  • A transitional cell carcinoma (TCC) was chemically induced by intravesical installation of methyl-nitrosurea (MNU) in the bladder of female Fischer 344 rats.
  • For treatment, a dose of 100 mg/kg CAI dissolved in PEG-400 vehicle was chosen.
  • Under CAI treatment, the apoptotic rate in tumors increased, whereas the proliferation rate decreased, as shown by TUNEL assay and KI-67-immunhistochemistry, respectively.
  • This animal model confirms the anti-tumor effect of CAI and shows induction of apoptosis and growth inhibition in bladder cancer by the drug.
  • [MeSH-major] Antineoplastic Agents / pharmacology. Apoptosis / drug effects. Carcinoma, Transitional Cell / drug therapy. Carcinoma, Transitional Cell / pathology. Triazoles / pharmacology. Urinary Bladder Neoplasms / drug therapy. Urinary Bladder Neoplasms / pathology
  • [MeSH-minor] Animals. Carcinogens. Cell Proliferation / drug effects. Female. Methylnitrosourea. Rats. Rats, Inbred F344

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  • (PMID = 15868902.001).
  • [ISSN] 0250-7005
  • [Journal-full-title] Anticancer research
  • [ISO-abbreviation] Anticancer Res.
  • [Language] eng
  • [Publication-type] Journal Article; Research Support, Non-U.S. Gov't
  • [Publication-country] Greece
  • [Chemical-registry-number] 0 / Antineoplastic Agents; 0 / Carcinogens; 0 / Triazoles; 684-93-5 / Methylnitrosourea; 99519-84-3 / carboxyamido-triazole
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4. Sejima T, Isoyama T, Miyagawa I: Comparative study of apoptotic antitumor effect between angiogenesis inhibitor AGM-1470 and MVAC chemotherapy on rat urinary bladder cancer. Urol Int; 2004;73(3):226-33
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  • [Title] Comparative study of apoptotic antitumor effect between angiogenesis inhibitor AGM-1470 and MVAC chemotherapy on rat urinary bladder cancer.
  • OBJECTIVES: To investigate the antitumor apoptotic effect of AGM-1470 by comparing it to that induced by methotrexate, vinblastine, doxorubicin, and cisplatin (MVAC) therapy, currently the standard chemotherapy for bladder cancer, in a rat bladder cancer model.
  • MATERIALS AND METHODS: A total of 45 six-week-old female rats were divided into 3 equal groups: those receiving AGM-1470 treatment; those receiving MVAC treatment, and controls.
  • All rats were cystectomized to evaluate the therapeutic effect with regard to macroscopic tumor findings, hematoxylin and eosin pathology, apoptosis detection, and immunohistochemistry (IHC) for bcl-2.
  • RESULTS: Our experimental protocol succeeded in producing invasive bladder tumors in the majority of rats.
  • Tumor volume was significantly reduced in the AGM-1470 and MVAC treatment groups compared with that in the control group.
  • The apoptotic indices of tumor cells was significantly higher in the AGM-1470 and MVAC treatment groups than in the control group.
  • CONCLUSIONS: AGM-1470 and MVAC appear to exert a prominent mass reduction effect via tumor cell apoptosis in cases of invasive bladder tumor, although these therapies did not demonstrate any obvious modulation of bcl-2 protein expression status.
  • Bcl-2 overexpression might be an obstacle to AGM-1470 therapy because of its significant inhibitory effect on apoptosis.
  • [MeSH-major] Angiogenesis Inhibitors / therapeutic use. Antineoplastic Combined Chemotherapy Protocols / therapeutic use. Carcinoma, Transitional Cell / drug therapy. Cisplatin / therapeutic use. Doxorubicin / therapeutic use. Methotrexate / therapeutic use. Sesquiterpenes / therapeutic use. Urinary Bladder Neoplasms / drug therapy. Vinblastine / therapeutic use
  • [MeSH-minor] Animals. Apoptosis / drug effects. Carcinoma, Squamous Cell / drug therapy. Cyclohexanes. Female. Gene Expression. Genes, bcl-2. Hyperplasia. Models, Animal. Papilloma / drug therapy. Rats. Rats, Wistar. Treatment Outcome. Urinary Bladder / pathology

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  • [Copyright] copyright 2004 S. Karger AG, Basel
  • (PMID = 15539841.001).
  • [ISSN] 0042-1138
  • [Journal-full-title] Urologia internationalis
  • [ISO-abbreviation] Urol. Int.
  • [Language] eng
  • [Publication-type] Comparative Study; Evaluation Studies; Journal Article
  • [Publication-country] Switzerland
  • [Chemical-registry-number] 0 / Angiogenesis Inhibitors; 0 / Cyclohexanes; 0 / Sesquiterpenes; 129298-91-5 / O-(chloroacetylcarbamoyl)fumagillol; 5V9KLZ54CY / Vinblastine; 80168379AG / Doxorubicin; Q20Q21Q62J / Cisplatin; YL5FZ2Y5U1 / Methotrexate; M-VAC protocol
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5. Derycke AS, Kamuhabwa A, Gijsens A, Roskams T, De Vos D, Kasran A, Huwyler J, Missiaen L, de Witte PA: Transferrin-conjugated liposome targeting of photosensitizer AlPcS4 to rat bladder carcinoma cells. J Natl Cancer Inst; 2004 Nov 3;96(21):1620-30
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  • [Title] Transferrin-conjugated liposome targeting of photosensitizer AlPcS4 to rat bladder carcinoma cells.
  • BACKGROUND: The efficacy and safety of photodynamic therapy for superficial bladder cancer depend on tumor-selective accumulation of the photosensitizer.
  • Bladder transitional-cell carcinoma cells overexpress the transferrin receptor on their surface.
  • The accumulation of free AlPcS4, Lip-AlPcS4, and Tf-Lip-AlPcS4 in human AY-27 transitional-cell carcinoma cells and in an orthotopic rat bladder tumor model was visualized by fluorescence microscopy.
  • In vitro AlPcS4 accumulation was quantified by fluorescence measurements following drug extraction, and the photodynamic efficacy of AlPcS4 was measured in a clonogenic assay.
  • Among rats bearing AY-27 cell-derived bladder tumors, intravesical instillation with Tf-Lip-AlPcS4 resulted in mean AlPcS4 fluorescence in tumoral tissue, normal urothelium, and submucosa/muscle of 77.9 fluorescence units (fu) (95% CI = 69.1 to 86.8 fu), 4.3 fu (95% CI = 4.0 to 4.5 fu), and 1.0 (95% CI = 0.1 to 1.9 fu), respectively, whereas instillation of free AlPcS4 resulted in nonselective accumulation throughout the whole bladder wall, and Lip-AlPcS4 instillation resulted in no tissue accumulation.
  • Photodynamic therapy of AY-27 cells incubated with Lip-AlPcS4 resulted in cell viabilities greater than 90% for all concentrations and incubation times tested; photodynamic therapy of cells incubated with 1 muM Tf-Lip-AlPcS4 or AlPcS4 resulted in cell viabilities of 0.19% (95% CI = 0.02% to 0.36%) and 1.32% (95% CI = 0.46% to 2.19%), respectively.
  • Higher concentrations of either AlPcS4 or Tf-Lip-AlPcS4 resulted in cell kills of more than 3 logs.
  • CONCLUSIONS: Transferrin-mediated liposomal targeting of photosensitizing drugs is a promising potential tool for photodynamic therapy of superficial bladder tumors.
  • [MeSH-major] Antineoplastic Agents / pharmacology. Carcinoma, Transitional Cell / drug therapy. Indoles / pharmacology. Organometallic Compounds / pharmacology. Photochemotherapy / methods. Photosensitizing Agents / pharmacology. Urinary Bladder Neoplasms / drug therapy

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  • (PMID = 15523091.001).
  • [ISSN] 1460-2105
  • [Journal-full-title] Journal of the National Cancer Institute
  • [ISO-abbreviation] J. Natl. Cancer Inst.
  • [Language] eng
  • [Publication-type] Journal Article; Research Support, Non-U.S. Gov't
  • [Publication-country] United States
  • [Chemical-registry-number] 0 / Antineoplastic Agents; 0 / Indoles; 0 / Liposomes; 0 / Organometallic Compounds; 0 / Photosensitizing Agents; 0 / Receptors, Transferrin; 0 / Transferrin; 122170-90-5 / aluminum tetrasulfophthalocyanine; 30IQX730WE / Polyethylene Glycols
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6. Kamuhabwa AR, Agostinis P, D'Hallewin MA, Kasran A, de Witte PA: Photodynamic activity of hypericin in human urinary bladder carcinoma cells. Anticancer Res; 2000 Jul-Aug;20(4):2579-84
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  • [Title] Photodynamic activity of hypericin in human urinary bladder carcinoma cells.
  • Recently, we reported the selective accumulation of hypericin in transitional cell carcinoma cells following intravesical instillation of hypericin in humans.
  • This observation infers that hypericin, a potent photosensitizer, could be used as a selective PDT (photodynamic therapy) tool against superficial bladder cancer.
  • The aim of the present study was to investigate in vitro whether hypericin exhibits specific affinity for TCC transitional cell carcinoma) bladder cells and to assess its photocytotoxic effect.
  • Three human TCC cell lines (J-82, T-24 and RT-4), a chemically induced rat TCC cell line (NBT-II), but also non-bladder carcinoma cells (HeLa, A431, MCF-7 and MCF-***ADR) and normal cells (HEL229, RPE and PHK), were used in this comparative study.
  • Flow cytometric analysis of cells treated with different hypericin-containing vehicles for various incubation times (2 hours or 24 hours) indicated that short exposure of the cells (2 hours) to hypericin in the absence of serum results in the highest intracellular accumulation of the compound.
  • As expected, prolonging the incubation time increased both the cellular accumulation and photocytoxicity of hypericia.
  • With the exception of the RT-4 and MCF-7 cells (which were less sensitive to hypericin), all the other carcinoma cell lines examined showed equal sensitivity to the photoactivated hypericia, independently of their histological origin (bladder or non-bladder).
  • This suggests that in vivo factors other than the cancer cells themselves are responsible for the specific accumulation of hypericin in urothelial carcinoma lesions.
  • [MeSH-major] Antineoplastic Agents / pharmacology. Carcinoma, Transitional Cell / drug therapy. Perylene / analogs & derivatives. Photochemotherapy. Urinary Bladder Neoplasms / drug therapy
  • [MeSH-minor] Drug Resistance, Neoplasm. Fluorescence. Humans. Tumor Cells, Cultured

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  • (PMID = 10953329.001).
  • [ISSN] 0250-7005
  • [Journal-full-title] Anticancer research
  • [ISO-abbreviation] Anticancer Res.
  • [Language] eng
  • [Publication-type] Journal Article
  • [Publication-country] GREECE
  • [Chemical-registry-number] 0 / Antineoplastic Agents; 5QD5427UN7 / Perylene; 7V2F1075HD / hypericin
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7. Perabo FG, Willert PL, Wirger A, Schmidt DH, Wardelmann E, Sitzia M, von Ruecker A, Mueller SC: Preclinical evaluation of superantigen (staphylococcal enterotoxin B) in the intravesical immunotherapy of superficial bladder cancer. Int J Cancer; 2005 Jul 1;115(4):591-8
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  • [Title] Preclinical evaluation of superantigen (staphylococcal enterotoxin B) in the intravesical immunotherapy of superficial bladder cancer.
  • In this study, we evaluated a new approach for the intravesical therapy of superficial bladder cancer.
  • We investigated in coculture experiments if staphylococcal enterotoxin B (SEB)-activated PBMCs are able to induce apoptosis in human transitional cell carcinoma (TCC) cells.
  • Additionally, we tested the toxicity and efficacy of SEB dissolved in NaCl 0.9% administered intravesically once weekly for 6 weeks in a rat bladder cancer model.
  • To validate the coculture in vitro findings, we evaluated tumor stage, grade, apoptotic cells in the urothelium and stroma of the bladder and infiltration of the bladder wall by lymphocytes, macrophages and mononuclear cells.
  • The remaining tumors of the therapy group showed a significant amount of apoptosis and granulocytes, mainly in the urothelium, whereas no relevant apoptosis or infiltration of the bladder with lymphocytes or macrophages was found in the control group.
  • [MeSH-major] Antigens, Bacterial / therapeutic use. Enterotoxins / therapeutic use. Urinary Bladder Neoplasms / drug therapy
  • [MeSH-minor] Animals. Apoptosis / drug effects. Cell Line, Tumor. Coculture Techniques. Disease Models, Animal. Female. Humans. Immunotherapy / methods. Jurkat Cells. Leukocytes, Mononuclear / drug effects. Rats. Rats, Inbred F344

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  • [Copyright] Copyright 2005 Wiley-Liss, Inc.
  • (PMID = 15704106.001).
  • [ISSN] 0020-7136
  • [Journal-full-title] International journal of cancer
  • [ISO-abbreviation] Int. J. Cancer
  • [Language] eng
  • [Publication-type] Journal Article; Research Support, Non-U.S. Gov't
  • [Publication-country] United States
  • [Chemical-registry-number] 0 / Antigens, Bacterial; 0 / Enterotoxins; 39424-53-8 / enterotoxin B, staphylococcal
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8. Wirger A, Perabo FG, Burgemeister S, Haase L, Schmidt DH, Doehn C, Mueller SC, Jocham D: Flavopiridol, an inhibitor of cyclin-dependent kinases, induces growth inhibition and apoptosis in bladder cancer cells in vitro and in vivo. Anticancer Res; 2005 Nov-Dec;25(6B):4341-7
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  • [Title] Flavopiridol, an inhibitor of cyclin-dependent kinases, induces growth inhibition and apoptosis in bladder cancer cells in vitro and in vivo.
  • It has been shown to inhibit cyclin-dependent kinases (CDKs), causing cell cycle arrest and growth inhibition.
  • Flavopiridol is reported to have cytotoxic activity against a wide range of cancer cell lines and has demonstrated its efficacy in several clinical trials.
  • Flavopiridol seems a well-suited potential new agent for the treatment of bladder cancer.
  • We, therefore, evaluated whether flavopiridol inhibits growth and induces apoptosis in bladder cancer cells and additionally examined the toxicity and efficacy of this drug in vivo in a rat bladder cancer model.
  • The in vitro experiments showed an IC20 of 50-100 nM in all cell lines tested.
  • The IC50 was found to be 150-350 nM in the well-differentiated RT4 and RTI12 cell lines after treatment with flavopiridol, in comparison to a IC50 of 1000 nMfor the poorly-differentiated cell lines T24 and SUP.
  • After exposure to flavopiridol, all tumor cell lines underwent significant apoptosis in comparison to untreated cells, beginning at a dose of 50 nM flavopiridol.
  • The treatment of rat urinary bladder cancer with flavopiridol demonstrated the best efficacy with an intermittent treatment of 0.1 mg/kg, 3 times weekly over a total of 3 weeks, resulting in 7/12 animals tumor-free and a trend for the remaining tumors to have lower stage and grade.
  • In summary, our results indicated that flavopiridol could be a useful therapeutic agent for bladder cancer, inhibiting tumor growth, malignant progression and inducing apoptosis.
  • [MeSH-major] Antineoplastic Agents / pharmacology. Carcinoma, Transitional Cell / drug therapy. Flavonoids / pharmacology. Piperidines / pharmacology. Urinary Bladder Neoplasms / drug therapy
  • [MeSH-minor] Animals. Apoptosis / drug effects. Cell Growth Processes / drug effects. Cell Line, Tumor. Cyclin-Dependent Kinases / antagonists & inhibitors. Dose-Response Relationship, Drug. Female. Flow Cytometry. Humans. Protein Kinase Inhibitors / pharmacology. Rats. Rats, Inbred F344

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  • (PMID = 16309238.001).
  • [ISSN] 0250-7005
  • [Journal-full-title] Anticancer research
  • [ISO-abbreviation] Anticancer Res.
  • [Language] eng
  • [Publication-type] Journal Article
  • [Publication-country] Greece
  • [Chemical-registry-number] 0 / Antineoplastic Agents; 0 / Flavonoids; 0 / Piperidines; 0 / Protein Kinase Inhibitors; 45AD6X575G / alvocidib; EC 2.7.11.22 / Cyclin-Dependent Kinases
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9. Shibata MA, Horiguchi T, Morimoto J, Otsuki Y: Massive apoptotic cell death in chemically induced rat urinary bladder carcinomas following in situ HSVtk electrogene transfer. J Gene Med; 2003 Mar;5(3):219-31
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  • [Title] Massive apoptotic cell death in chemically induced rat urinary bladder carcinomas following in situ HSVtk electrogene transfer.
  • BACKGROUND: Gene delivery in current gene therapy studies relies largely on recombinant viral vectors.
  • The effectiveness of in vivo electrogene transfer as a means of gene therapy for rat bladder cancers using the herpes simplex virus 1 thymidine kinase (HSVtk) gene in combination with ganciclovir (GCV) was therefore investigated.
  • METHODS: The killing effects of HSVtk/GCV therapy were evaluated in transitional cell carcinoma (TCC) cells in vitro and in vivo.
  • In animal experiments, electrogene transfer of HSVtk into N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN)-induced rat bladder tumors was conducted followed by GCV administration.
  • RESULTS: In vitro studies demonstrated that approximately 50-70% of the TCC cells died as a result of transfection with pHSVtk and GCV administration and that this treatment was associated with decreased DNA synthesis and elevated activities of caspase-3, -8 and -9.
  • A direct single injection of HSVtk into bladder tumors using in vivo electrogene transfer followed by GCV i.p. administration resulted in significant increases in the levels of apoptosis and histopathological necrosis accompanied by marked inflammation.
  • Active caspase-3 was strongly expressed in the cell death areas of the TCC in rats given pHSVtk/GCV therapy.
  • CONCLUSIONS: In vivo electrogene transfer results in efficient gene transfer in BBN-induced rat bladder tumors and the HSVtk/GCV prodrug system induces significant cell death which appears to be, at least, mediated via the mitochondrial apoptotic pathway.
  • [MeSH-major] Antiviral Agents / pharmacology. Apoptosis / drug effects. Carcinoma / physiopathology. Ganciclovir / pharmacology. Proto-Oncogene Proteins c-bcl-2. Thymidine Kinase / genetics. Urinary Bladder Neoplasms / physiopathology

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  • [Copyright] Copyright 2002 John Wiley & Sons, Ltd.
  • (PMID = 12666188.001).
  • [ISSN] 1099-498X
  • [Journal-full-title] The journal of gene medicine
  • [ISO-abbreviation] J Gene Med
  • [Language] eng
  • [Publication-type] Journal Article; Research Support, Non-U.S. Gov't
  • [Publication-country] England
  • [Chemical-registry-number] 0 / Antiviral Agents; 0 / Proto-Oncogene Proteins; 0 / Proto-Oncogene Proteins c-bcl-2; 0 / bcl-2-Associated X Protein; EC 2.7.1.21 / Thymidine Kinase; P9G3CKZ4P5 / Ganciclovir
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10. Gronlund-Pakkanen S, Wahlfors J, Makinen K, Pakkanen TM, Talja M, Ala-Opas M, Alhava E, Moore RB: The fluorescence biodistribution and kinetics of aminolevulinic acid induced protoporphyrin IX in the bladder of a rat model with orthotopic urothelial carcinoma. J Urol; 2002 Apr;167(4):1848-53
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  • [Title] The fluorescence biodistribution and kinetics of aminolevulinic acid induced protoporphyrin IX in the bladder of a rat model with orthotopic urothelial carcinoma.
  • PURPOSE: Photodynamic therapy is an alternative intravesical therapy modality for superficial bladder cancer.
  • We compared intravenous versus intravesical administration of ALA and established the proper timing and dose of ALA for photodynamic therapy.
  • To characterize the distribution of ALA in rat bladder tumor and normal bladder layers a cooled charge coupled device camera was used.
  • Three areas of urothelium, submucosa and muscularis of the bladder wall were chosen for analysis.
  • The difference in fluorescence intensity in tumor tissue to normal urothelium was 2:1 to 3:1 at 2 hours.
  • CONCLUSIONS: According to the results of this study a difference in PpIX accumulation in urothelial carcinoma or normal urothelium and the muscular layer of the bladder can be achieved by each route of ALA administration.
  • The effect of this finding on clinical therapy results remains to be resolved in the future.
  • [MeSH-major] Aminolevulinic Acid / pharmacokinetics. Carcinoma, Transitional Cell / drug therapy. Photochemotherapy. Photosensitizing Agents / pharmacokinetics. Protoporphyrins / metabolism. Urinary Bladder Neoplasms / drug therapy
  • [MeSH-minor] Administration, Intravesical. Animals. Female. Fluorescence. Injections, Intravenous. Rats. Rats, Inbred F344. Tissue Distribution

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  • (PMID = 11912446.001).
  • [ISSN] 0022-5347
  • [Journal-full-title] The Journal of urology
  • [ISO-abbreviation] J. Urol.
  • [Language] eng
  • [Publication-type] Comparative Study; Journal Article
  • [Publication-country] United States
  • [Chemical-registry-number] 0 / Photosensitizing Agents; 0 / Protoporphyrins; 553-12-8 / protoporphyrin IX; 88755TAZ87 / Aminolevulinic Acid
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11. Zhang X, Yamashita M, Uetsuki H, Kakehi Y: Short-term effects of TNP-470 in combination with cisplatin in the rat model of bladder cancer. In Vivo; 2002 Sep-Oct;16(5):293-7
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  • [Title] Short-term effects of TNP-470 in combination with cisplatin in the rat model of bladder cancer.
  • PURPOSE: To investigate the short-term effects of TNP-470 in combination with cisplatin in a rat model of bladder cancer.
  • MATERIALS AND METHODS: Following treatment of TNP-470 with or without cisplatin for 7 days, the states of angiogenesis, apoptosis and cell proliferation were evaluated in rat bladder cancer induced by N-butyl-N-(4-hydroxybutyl) nitrosamine.
  • RESULTS: In comparison with untreated tumors, we noted a significantly decreased microvessel density (MVD) in the rat bladder cancer treated by TNP-470, and a significantly increased apoptotic index (AI) when treated by cisplatin.
  • In TNP-470 plus cisplatin-treated tumors, both significantly decreased MVD and increased AI were observed in non-invasive and invasive rat bladder cancers in addition to a significantly decreased proliferation index (PI) in invasive cancer.
  • CONCLUSION: The combination therapy of TNP-470 with cisplatin may act through both the inhibition of angiogenesis and induction of apoptosis, and invasive tumor cells may be much more sensitive to this combined therapy in rat bladder cancer.
  • [MeSH-major] Angiogenesis Inhibitors / therapeutic use. Antibiotics, Antineoplastic / therapeutic use. Carcinoma, Transitional Cell / drug therapy. Cisplatin / therapeutic use. Sesquiterpenes / therapeutic use. Urinary Bladder Neoplasms / drug therapy
  • [MeSH-minor] Animals. Antigens, CD31 / analysis. Apoptosis / drug effects. Cell Division / drug effects. Cyclohexanes. DNA, Neoplasm / analysis. Disease Models, Animal. Drug Therapy, Combination. Immunoenzyme Techniques. In Situ Nick-End Labeling. Ki-67 Antigen / analysis. Microcirculation / drug effects. Neoplasm Invasiveness / pathology. Neoplasm Invasiveness / prevention & control. Rats. Rats, Wistar

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  • (PMID = 12494866.001).
  • [ISSN] 0258-851X
  • [Journal-full-title] In vivo (Athens, Greece)
  • [ISO-abbreviation] In Vivo
  • [Language] eng
  • [Publication-type] Journal Article
  • [Publication-country] Greece
  • [Chemical-registry-number] 0 / Angiogenesis Inhibitors; 0 / Antibiotics, Antineoplastic; 0 / Antigens, CD31; 0 / Cyclohexanes; 0 / DNA, Neoplasm; 0 / Ki-67 Antigen; 0 / Sesquiterpenes; 129298-91-5 / O-(chloroacetylcarbamoyl)fumagillol; Q20Q21Q62J / Cisplatin
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12. Kong C, Zhu Y, Sun C, Li Z, Sun Z, Zhang X, Takanaka I: Inhibition of tumor angiogenesis during cisplatin chemotherapy for bladder cancer improves treatment outcome. Urology; 2005 Feb;65(2):395-9
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  • [Title] Inhibition of tumor angiogenesis during cisplatin chemotherapy for bladder cancer improves treatment outcome.
  • OBJECTIVES: To investigate the effect of inhibiting tumor angiogenesis during cisplatinum-(II)-diamine dichloride (cisplatin) chemotherapy of bladder cancer (BC) in a rat model.
  • METHODS: Bladder cancer was induced in 64 male rats using 0.05% N-butyl-N-(4-hydroxybutyl)-nitrosamine in their water supply for 20 weeks.
  • The animals were then divided randomly into four groups of 16 rats each: a control BC group (group 1); a BC group treated with cisplatin (0.25 mg/kg body weight) by intraperitoneal injection twice every week (group 2); a BC group treated with the antiangiogenic factor TNP-470 (30 mg/kg body weight) by intraperitoneal injection twice every week (group 3); and a BC group treated with cisplatin plus TNP-470 (group 4, treatment regimens as described).
  • Per group, 4 rats were killed weekly after the start of treatment, for 4 weeks.
  • BC was confirmed using histologic characteristics, and the treatment outcomes were determined by measuring tumor microvascular density and cell proliferation and apoptosis indexes (PI and AI, respectively).
  • CONCLUSIONS: TNP-470 in conjunction with cisplatin chemotherapy resulted in a decrease in the microvascular density of BC in a rat model.
  • However, TNP-470 did not appear to have a significant impact on the cisplatin effect against BC as measured by apoptosis and cell proliferation.
  • [MeSH-major] Antineoplastic Combined Chemotherapy Protocols / therapeutic use. Carcinoma, Transitional Cell / drug therapy. Neovascularization, Pathologic / drug therapy. Urinary Bladder Neoplasms / drug therapy
  • [MeSH-minor] Angiogenesis Inhibitors / administration & dosage. Animals. Antibiotics, Antineoplastic / administration & dosage. Antineoplastic Agents, Alkylating / administration & dosage. Apoptosis. Cisplatin / administration & dosage. Combined Modality Therapy. Cyclohexanes. Drug Screening Assays, Antitumor. Drug Synergism. Injections, Intraperitoneal. Male. Random Allocation. Rats. Sesquiterpenes / administration & dosage

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  • (PMID = 15708074.001).
  • [ISSN] 1527-9995
  • [Journal-full-title] Urology
  • [ISO-abbreviation] Urology
  • [Language] eng
  • [Publication-type] Comparative Study; Journal Article
  • [Publication-country] United States
  • [Chemical-registry-number] 0 / Angiogenesis Inhibitors; 0 / Antibiotics, Antineoplastic; 0 / Antineoplastic Agents, Alkylating; 0 / Cyclohexanes; 0 / Sesquiterpenes; 129298-91-5 / O-(chloroacetylcarbamoyl)fumagillol; Q20Q21Q62J / Cisplatin
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13. El Khatib S, Didelon J, Leroux A, Bezdetnaya L, Notter D, D'Hallewin M: Kinetics, biodistribution and therapeutic efficacy of hexylester 5-aminolevulinate induced photodynamic therapy in an orthotopic rat bladder tumor model. J Urol; 2004 Nov;172(5 Pt 1):2013-7
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  • [Title] Kinetics, biodistribution and therapeutic efficacy of hexylester 5-aminolevulinate induced photodynamic therapy in an orthotopic rat bladder tumor model.
  • PURPOSE: To optimize photodynamic therapy (PDT) we investigated the kinetics and biodistribution of hexylester 5-aminolevulinate (hALA) induced protoporphyrin IX (PpIX) and the therapeutic efficacy of PDT at different drug and light doses in an orthotopic rat bladder tumor model.
  • PDT efficacy at different fluences (15 to 80 J/cm2) was histologically assessed 48 hours and 1 week after treatment.
  • Within the same tumor bearing animal the same fluorescence levels were observed in normal epithelium and transitional cell carcinoma, whereas the tumor-to-muscle ratio was 3.
  • Tumor necrosis with an intact normal bladder wall was observed with a fluence of 20 J/cm2 for 8 mM hALA, while 15 J/cm2 was ineffective and 25 J/cm2 induced total wall necrosis.
  • Thus, fluorescence does not necessarily predict the therapeutic efficacy of PDT.
  • [MeSH-major] Aminolevulinic Acid / analogs & derivatives. Aminolevulinic Acid / pharmacokinetics. Aminolevulinic Acid / therapeutic use. Carcinoma, Transitional Cell / drug therapy. Disease Models, Animal. Photochemotherapy. Tissue Distribution. Urinary Bladder Neoplasms / drug therapy

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  • (PMID = 15540780.001).
  • [ISSN] 0022-5347
  • [Journal-full-title] The Journal of urology
  • [ISO-abbreviation] J. Urol.
  • [Language] eng
  • [Publication-type] Journal Article; Research Support, Non-U.S. Gov't
  • [Publication-country] United States
  • [Chemical-registry-number] 88755TAZ87 / Aminolevulinic Acid; G7H20TKI67 / 5-aminolevulinic acid hexyl ester
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14. Kilani RT, Tamimi Y, Karmali S, Mackey J, Hanel EG, Wong KK, Moore RB: Selective cytotoxicity of gemcitabine in bladder cancer cell lines. Anticancer Drugs; 2002 Jul;13(6):557-66
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  • [Title] Selective cytotoxicity of gemcitabine in bladder cancer cell lines.
  • We have examined the cytotoxic effect of gemcitabine in intravesical therapy using an in vitro co-cultured spheroid model composed of transitional cell carcinoma (TCC) and fibroblasts from both human and rat species.
  • Spheroids composed of human TCC and fibroblasts (MGH-U3/CRL-1120 or RT-112/CRL-1120) as well as rat TCC and their corresponding fibroblasts (AY-27/RF-Ed1) displayed the same drug tolerance profile after an exposure of 0, 1, 3, 5, 7 and 14 days.
  • As confirmed by time-lapse photography, MTT essay and vital dye staining, gemcitabine selectively killed the human and rat bladder cancer cell lines, but did not affect un-transformed human and rat fibroblast lines.
  • [MeSH-major] Antimetabolites, Antineoplastic / pharmacology. Deoxycytidine / analogs & derivatives. Deoxycytidine / pharmacology. Urinary Bladder Neoplasms / pathology
  • [MeSH-minor] Animals. Cell Line. Cell Survival / drug effects. Coculture Techniques. Coloring Agents. Fibroblasts. Humans. Immunohistochemistry. Rats. Spheroids, Cellular / drug effects. Tetrazolium Salts. Thiazoles. Tumor Cells, Cultured. Tumor Stem Cell Assay

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  • (PMID = 12172501.001).
  • [ISSN] 0959-4973
  • [Journal-full-title] Anti-cancer drugs
  • [ISO-abbreviation] Anticancer Drugs
  • [Language] eng
  • [Publication-type] Journal Article
  • [Publication-country] England
  • [Chemical-registry-number] 0 / Antimetabolites, Antineoplastic; 0 / Coloring Agents; 0 / Tetrazolium Salts; 0 / Thiazoles; 0W860991D6 / Deoxycytidine; 298-93-1 / thiazolyl blue; B76N6SBZ8R / gemcitabine
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15. Xiao Z, Brown K, Tulip J, Moore RB: Whole bladder photodynamic therapy for orthotopic superficial bladder cancer in rats: a study of intravenous and intravesical administration of photosensitizers. J Urol; 2003 Jan;169(1):352-6
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  • [Title] Whole bladder photodynamic therapy for orthotopic superficial bladder cancer in rats: a study of intravenous and intravesical administration of photosensitizers.
  • PURPOSE: Photodynamic therapy after intravenous injection of Photofrin (QLT Phototherapeutics, Vancouver, British Columbia, Canada) results in a contracted bladder and skin photosensitivity, which limits its clinical application.
  • In an attempt to overcome these limitations photodynamic therapy after intravesical instillation of Photofrin or 5-aminolevulinic acid (ALA) in an orthotopic rat bladder tumor model was explored and compared with intravenous Photofrin for photodynamic therapy efficacy and phototoxicity.
  • MATERIALS AND METHODS: At 2 weeks after bladder implantation of 1.5 x 10(6) AY-27 tumor cells animals were randomly grouped.
  • Whole bladder photodynamic therapy with graded doses of light (lambda = 630 nm.) was performed 4 hours after drug administration.
  • RESULTS: Photodynamic therapy with intravenous Photofrin plus 100 J./cm.(2) light resulted in severe bladder damage.
  • There were no photodynamic therapy related deaths in groups receiving intravesical instillation of Photofrin or ALA that also received 50 to 100 J./cm.(2) Median survival in rats treated with ALA intravesically plus 75 J./cm.(2) (77 days), Photofrin intravesically plus 50 (67) or 100 J./cm.(2) (76) and Photofrin intravenously plus 50 J./cm.(2) (60) were significantly different from that in controls (44).
  • CONCLUSIONS: Intravesical instillation of Photofrin or ALA can achieve the same photodynamic therapy efficacy as intravenous Photofrin in this orthotopic rat bladder tumor model with less phototoxicity to normal tissues.
  • [MeSH-major] Carcinoma, Transitional Cell / drug therapy. Photochemotherapy. Photosensitizing Agents / administration & dosage. Urinary Bladder Neoplasms / drug therapy
  • [MeSH-minor] Administration, Intravesical. Aminolevulinic Acid / administration & dosage. Aminolevulinic Acid / adverse effects. Animals. Antineoplastic Agents / administration & dosage. Antineoplastic Agents / adverse effects. Dihematoporphyrin Ether / administration & dosage. Dihematoporphyrin Ether / adverse effects. Female. Injections, Intravenous. Neoplasm Transplantation. Rats. Rats, Inbred F344. Tumor Cells, Cultured. Urinary Bladder / physiopathology

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  • (PMID = 12478188.001).
  • [ISSN] 0022-5347
  • [Journal-full-title] The Journal of urology
  • [ISO-abbreviation] J. Urol.
  • [Language] eng
  • [Publication-type] Comparative Study; Journal Article; Research Support, Non-U.S. Gov't
  • [Publication-country] United States
  • [Chemical-registry-number] 0 / Antineoplastic Agents; 0 / Photosensitizing Agents; 88755TAZ87 / Aminolevulinic Acid; 97067-70-4 / Dihematoporphyrin Ether
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16. Kemberling JK, Hampton JA, Keck RW, Gomez MA, Selman SH: Inhibition of bladder tumor growth by the green tea derivative epigallocatechin-3-gallate. J Urol; 2003 Sep;170(3):773-6
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  • [Title] Inhibition of bladder tumor growth by the green tea derivative epigallocatechin-3-gallate.
  • PURPOSE: We evaluated the green tea derivative epigallocatechin-3-gallate (EGCG) as an intravesical agent for the prevention of transitional cell tumor implantation.
  • MATERIALS AND METHODS: In vitro studies were performed in the AY-27 rat transitional cell cancer and the L1210 mouse leukemia cell lines.
  • Surviving cell colonies were then determined.
  • A DNA ladder assay was performed in the 2 cell lines.
  • Rats were sacrificed 3 weeks following treatment.
  • RESULTS: At 6.0 x 104 cells per 100 mm dish a time dose dependent response was observed.
  • After 2 hours of treatment with EGCG 100% cell lethality of the AY-27 cell line occurred at concentrations greater than 100 microM.
  • Strong banding on the DNA ladder assay was seen with the L1210 mouse leukemia cell line.
  • Only weak banding patterns were found in the AY-27 cell line treated with EGCG (100 and 200 microM) for 24 hours.
  • CONCLUSIONS: The clonal assays showed a time dose related response to EGCG.
  • Intravesical instillation of EGCG inhibits the growth of AY-27 rat transitional cells implanted in this model.
  • [MeSH-major] Antineoplastic Agents, Phytogenic / therapeutic use. Carcinoma, Transitional Cell / drug therapy. Catechin / analogs & derivatives. Catechin / therapeutic use. Free Radical Scavengers / therapeutic use. Urinary Bladder Neoplasms / drug therapy
  • [MeSH-minor] Animals. Dose-Response Relationship, Drug. Rats. Rats, Inbred F344. Tea. Tumor Cells, Cultured

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  • (PMID = 12913695.001).
  • [ISSN] 0022-5347
  • [Journal-full-title] The Journal of urology
  • [ISO-abbreviation] J. Urol.
  • [Language] eng
  • [Publication-type] Journal Article; Research Support, Non-U.S. Gov't
  • [Publication-country] United States
  • [Chemical-registry-number] 0 / Antineoplastic Agents, Phytogenic; 0 / Free Radical Scavengers; 0 / Tea; 8R1V1STN48 / Catechin; BQM438CTEL / epigallocatechin gallate
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17. Griffiths JR, McIntyre DJ, Howe FA, McSheehy PM, Ojugo ASE, Rodrigues LM, Wadsworth P, Price NM, Lofts F, Nicholson G, Smid K, Noordhuis P, Peters GJ, Stubbs M: Issues of normal tissue toxicity in patient and animal studies--effect of carbogen breathing in rats after 5-fluorouracil treatment. Acta Oncol; 2001;40(5):609-14
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  • [Title] Issues of normal tissue toxicity in patient and animal studies--effect of carbogen breathing in rats after 5-fluorouracil treatment.
  • Non-invasive magnetic resonance spectroscopy (MRS) can be used in the clinic to monitor the pharmacokinetics of the chemotherapeutic drug 5-fluorouracil (5-FU) and the effects of modifiers.
  • We report two studies of 5-FU toxicity in normal tissue--one with patients and the other an animal study.
  • 1) 19F MRS signals from fluoronucleotides, cytotoxic anabolites of 5-FU metabolism, were observed in the livers of two patients treated with 5-FU for colorectal cancer, shown by computed tomography (CT) and ultrasound (US) to have no liver metastases.
  • This is the first report of non-invasive monitoring of toxic 5-FU metabolites in normal human tissues.
  • This study demonstrates that there were no significant effects of carbogen breathing on the levels of 5-FU and its metabolites in normal rat tissues, or on the histology of the tissues assessed after treatment.
  • [MeSH-minor] Adenocarcinoma / drug therapy. Adenocarcinoma / radiotherapy. Adenocarcinoma / secondary. Adenocarcinoma / surgery. Animals. Antimetabolites, Antineoplastic / therapeutic use. Biological Availability. Bone Marrow / chemistry. Bone Marrow / ultrastructure. Carcinoma, Transitional Cell. Colonic Neoplasms / drug therapy. Colonic Neoplasms / surgery. Colorectal Neoplasms / drug therapy. Colorectal Neoplasms / metabolism. Combined Modality Therapy. Fatal Outcome. Female. Fluorodeoxyuridylate / analysis. Humans. Intestine, Small / chemistry. Intestine, Small / ultrastructure. Leucovorin / therapeutic use. Liver / chemistry. Liver / radiography. Liver / ultrasonography. Liver / ultrastructure. Liver Neoplasms / secondary. Magnetic Resonance Imaging. Middle Aged. Neoplasms, Multiple Primary. Rats. Rats, Inbred WF. Sigmoid Neoplasms / drug therapy. Sigmoid Neoplasms / radiotherapy. Sigmoid Neoplasms / surgery. Tomography, X-Ray Computed. Urinary Bladder Neoplasms

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  • (PMID = 11669333.001).
  • [ISSN] 0284-186X
  • [Journal-full-title] Acta oncologica (Stockholm, Sweden)
  • [ISO-abbreviation] Acta Oncol
  • [Language] eng
  • [Publication-type] Case Reports; Journal Article; Research Support, Non-U.S. Gov't
  • [Publication-country] Norway
  • [Chemical-registry-number] 0 / Antimetabolites, Antineoplastic; 0 / Fluorine Radioisotopes; 134-46-3 / Fluorodeoxyuridylate; 142M471B3J / Carbon Dioxide; 8063-77-2 / carbogen; Q573I9DVLP / Leucovorin; S88TT14065 / Oxygen; U3P01618RT / Fluorouracil
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