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Article ; Online: Real-world evidence of multiple myeloma treated from 2013 to 2019 in the Hospital District of Helsinki and Uusimaa, Finland.

Vikkula, Johanna / Uusi-Rauva, Kristiina / Ranki, Tuuli / Toppila, Iiro / Aalto-Setälä, Maria / Pousar, Katariina / Vassilev, Lotta / Porkka, Kimmo / Silvennoinen, Raija / Brück, Oscar

Future oncology (London, England)

2023 Volume 19, Issue 30, Page(s) 2029–2043

Abstract: Background: ...

Abstract	Background:
MeSH term(s)	Adult ; Humans ; Multiple Myeloma/diagnosis ; Multiple Myeloma/epidemiology ; Multiple Myeloma/therapy ; Finland/epidemiology ; Hematopoietic Stem Cell Transplantation/adverse effects ; Stem Cell Transplantation ; Hospitals ; Retrospective Studies
Language	English
Publishing date	2023-10-13
Publishing country	England
Document type	Journal Article
ZDB-ID	2274956-1
ISSN	1744-8301 ; 1479-6694
ISSN (online)	1744-8301
ISSN	1479-6694
DOI	10.2217/fon-2023-0120
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Article ; Online: Retrospective, Registry-based, Cohort Investigation of Clinical Outcomes in Patients with Cutaneous Squamous Cell Carcinoma and Basal Cell Carcinoma in Finland.

Tuominen, Samuli / Ukkola-Vuoti, Liisa / Riihilä, Pilvi / Knuutila, Jaakko S / Kähäri, Veli-Matti / Lassenius, Mariann / Ranki, Tuuli / Pousar, Katariina / Vassilev, Lotta / Vuoti, Sauli / Mattila, Kalle

Acta dermato-venereologica

2022 Volume 102, Page(s) adv00693

Abstract: Most cases of keratinocyte cancer can be treated effectively with surgery. However, survival is reduced in patients with advanced disease. This retrospective cohort study evaluated overall survival of patients with invasive keratinocyte cancers, and high- ...

Abstract	Most cases of keratinocyte cancer can be treated effectively with surgery. However, survival is reduced in patients with advanced disease. This retrospective cohort study evaluated overall survival of patients with invasive keratinocyte cancers, and high-risk features for progression of the disease and mortality in Finnish patients in a real-world setting. A total of 43,143 patients with keratinocyte cancer types of basal cell carcinoma and 10,380 with cutaneous squamous cell carcinoma were identified nationwide. More detailed patient records were available for a subset of patients (basal cell carcinoma n = 5,020 and cutaneous squamous cell carcinoma n = 1,482) from a regional database. Fifty percent of patients with advanced cutaneous squamous cell carcinoma died approximately 4.5 years after diagnosis. Multivariable models suggested that risk factors for keratinocyte cancer progression were male sex, presence of comorbidities, immunosuppression, and pre-cancerous lesions, while risk factors for disease-specific mortality were advanced disease stage with immunosuppression, other malignancies, and consecutive surgical excisions. These results suggest that identifying patient and tumour factors associated with poor disease outcome could be important when determining appropriate treatment and follow-up; however, further studies are necessary.
MeSH term(s)	Carcinoma, Basal Cell/epidemiology ; Carcinoma, Basal Cell/surgery ; Carcinoma, Squamous Cell/epidemiology ; Carcinoma, Squamous Cell/surgery ; Cohort Studies ; Finland/epidemiology ; Humans ; Male ; Registries ; Retrospective Studies ; Skin Neoplasms/epidemiology ; Skin Neoplasms/surgery
Language	English
Publishing date	2022-04-08
Publishing country	Sweden
Document type	Journal Article
ZDB-ID	80007-7
ISSN	1651-2057 ; 0001-5555
ISSN (online)	1651-2057
ISSN	0001-5555
DOI	10.2340/actadv.v102.2073
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Article: Characterization of a novel OX40 ligand and CD40 ligand-expressing oncolytic adenovirus used in the PeptiCRAd cancer vaccine platform.

Ylösmäki, Erkko / Ylösmäki, Leena / Fusciello, Manlio / Martins, Beatriz / Ahokas, Petra / Cojoc, Hanne / Uoti, Arttu / Feola, Sara / Kreutzman, Anna / Ranki, Tuuli / Karbach, Julia / Viitala, Tapani / Priha, Petri / Jäger, Elke / Pesonen, Sari / Cerullo, Vincenzo

Molecular therapy oncolytics

2021 Volume 20, Page(s) 459–469

Abstract: Oncolytic viruses (OVs) have been shown to induce anti-cancer immunity and enhance cancer immunotherapies, such as immune checkpoint inhibitor therapies. OV therapies can be further improved by arming OVs with immunostimulatory molecules, including ... ...

Abstract	Oncolytic viruses (OVs) have been shown to induce anti-cancer immunity and enhance cancer immunotherapies, such as immune checkpoint inhibitor therapies. OV therapies can be further improved by arming OVs with immunostimulatory molecules, including various cytokines or chemokines. Here, we have developed a novel adenovirus encoding two immunostimulatory molecules: cluster of differentiation 40 ligand (CD40L) and tumor necrosis factor receptor superfamily member 4 ligand (OX40L). This novel virus, designated VALO-D102, is designed to activate both innate and adaptive immune responses against tumors. CD40L affects the innate side by licensing antigen-presenting cells to drive CD8
Language	English
Publishing date	2021-02-10
Publishing country	United States
Document type	Journal Article
ISSN	2372-7705
ISSN	2372-7705
DOI	10.1016/j.omto.2021.02.006
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Article ; Online: Serotype chimeric human adenoviruses for cancer gene therapy.

Ranki, Tuuli / Hemminki, Akseli

Viruses

2010 Volume 2, Issue 10, Page(s) 2196–2212

Abstract: Cancer gene therapy consists of numerous approaches where the common denominator is utilization of vectors for achieving therapeutic effect. A particularly potent embodiment of the approach is virotherapy, in which the replication potential of an ... ...

Abstract	Cancer gene therapy consists of numerous approaches where the common denominator is utilization of vectors for achieving therapeutic effect. A particularly potent embodiment of the approach is virotherapy, in which the replication potential of an oncolytic virus is directed towards tumor cells to cause lysis, while normal cells are spared. Importantly, the therapeutic effect of the initial viral load is amplified through viral replication cycles and production of progeny virions. All cancer gene therapy approaches rely on a sufficient level of delivery of the anticancer agent into target cells. Thus, enhancement of delivery to target cells, and reduction of delivery to non-target cells, in an approach called transductional targeting, is attractive. Both genetic and non-genetic retargeting strategies have been utilized. However, in the context of oncolytic viruses, it is beneficial to have the specific modification included in progeny virions and hence genetic modification may be preferable. Serotype chimerism utilizes serotype specific differences in receptor usage, liver tropism and seroprevalence in order to gain enhanced infection of target tissue. This review will focus on serotype chimeric adenoviruses for cancer gene therapy applications.
Language	English
Publishing date	2010-09-30
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2516098-9
ISSN	1999-4915 ; 1999-4915
ISSN (online)	1999-4915
ISSN	1999-4915
DOI	10.3390/v2102196
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Article ; Online: Serotype Chimeric Human Adenoviruses for Cancer GeneTherapy

Akseli Hemminki / Tuuli Ranki

Viruses, Vol 2, Iss 10, Pp 2196-

2010 Volume 2212

Abstract	Cancer gene therapy consists of numerous approaches where the common denominator is utilization of vectors for achieving therapeutic effect. A particularly potent embodiment of the approach is virotherapy, in which the replication potential of an oncolytic virus is directed towards tumor cells to cause lysis, while normal cells are spared. Importantly, the therapeutic effect of the initial viral load is amplified through viral replication cycles and production of progeny virions. All cancer gene therapy approaches rely on a sufficient level of delivery of the anticancer agent into target cells. Thus,enhancement of delivery to target cells, and reduction of delivery to non-target cells, in an approach called transductional targeting, is attractive. Both genetic and non-genetic retargeting strategies have been utilized. However, in the context of oncolytic viruses, it is beneficial to have the specific modification included in progeny virions and hence genetic modification may be preferable. Serotype chimerism utilizes serotype specific differences in receptor usage, liver tropism and seroprevalence in order to gain enhanced infection of target tissue. This review will focus on serotype chimeric adenoviruses for cancer gene therapy applications.
Keywords	adenoviruses ; serotype chimerism ; neutralizing antibodies ; tumor targeting ; liver detargeting ; Microbiology ; QR1-502 ; Science ; Q ; DOAJ:Microbiology ; DOAJ:Biology ; DOAJ:Biology and Life Sciences
Subject code	610
Language	English
Publishing date	2010-09-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Toxicological and bio-distribution profile of a GM-CSF-expressing, double-targeted, chimeric oncolytic adenovirus ONCOS-102 - Support for clinical studies on advanced cancer treatment.

Kuryk, Lukasz / Vassilev, Lotta / Ranki, Tuuli / Hemminki, Akseli / Karioja-Kallio, Aila / Levälampi, Onerva / Vuolanto, Antti / Cerullo, Vincenzo / Pesonen, Sari

PloS one

2017 Volume 12, Issue 8, Page(s) e0182715

Abstract: The purpose of this work was to carry out preclinical toxicity and bio-distribution studies required for regulatory approval of a clinical trial application for Phase I clinical studies of ONCOS-102 (Ad5/3-D24-GM-CSF) for therapy of advanced cancers ( ... ...

Abstract	The purpose of this work was to carry out preclinical toxicity and bio-distribution studies required for regulatory approval of a clinical trial application for Phase I clinical studies of ONCOS-102 (Ad5/3-D24-GM-CSF) for therapy of advanced cancers (NCT01598129). The study design, route of administration and dosage differs from the clinical protocol and in more detail, investigate bio-distribution and toxicological profile of ONCOS-102 treatment in animal model. The study was carried out in 300 hamsters divided into nine test groups-three bio-distribution groups and six groups for analysis of toxicity. Hamsters received ONCOS-102 by intracardial, intraperitoneal or subcutaneous injections. Additionally, one group was administered twice a week with intraperitoneal injections of Cyclophosphamide. The control animals were administered with NaCl solution without ONCOS-102 in the same volume and the same way. No adverse effects of repeated administration of ONCOS-102 including body weight, food consumption, hematology and clinical chemistry parameters, histopathology and bio-accumulation were observed in the course of 6-month administration and following 3- month recovery period. All obtained findings indicate the treatment clinically safe.
MeSH term(s)	Adenoviridae/genetics ; Animals ; Cricetinae ; Female ; Granulocyte-Macrophage Colony-Stimulating Factor/genetics ; Male ; Mesocricetus ; Molecular Targeted Therapy ; Neoplasms/therapy ; Oncolytic Virotherapy ; Oncolytic Viruses/genetics ; Tissue Distribution
Chemical Substances	Granulocyte-Macrophage Colony-Stimulating Factor (83869-56-1)
Language	English
Publishing date	2017-08-10
Publishing country	United States
Document type	Journal Article
ZDB-ID	2267670-3
ISSN	1932-6203 ; 1932-6203
ISSN (online)	1932-6203
ISSN	1932-6203
DOI	10.1371/journal.pone.0182715
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Article ; Online: Exploiting Preexisting Immunity to Enhance Oncolytic Cancer Immunotherapy.

Tähtinen, Siri / Feola, Sara / Capasso, Cristian / Laustio, Netta / Groeneveldt, Christianne / Ylösmäki, Erkko O / Ylösmäki, Leena / Martins, Beatriz / Fusciello, Manlio / Medeot, Marta / Tagliamonte, Maria / Chiaro, Jacopo / Hamdan, Firas / Peltonen, Karita / Ranki, Tuuli / Buonaguro, Luigi / Cerullo, Vincenzo

Cancer research

2020 Volume 80, Issue 12, Page(s) 2575–2585

Abstract: Because of the high coverage of international vaccination programs, most people worldwide have been vaccinated against common pathogens, leading to acquired pathogen-specific immunity with a robust memory T-cell repertoire. Although ... ...

Abstract	Because of the high coverage of international vaccination programs, most people worldwide have been vaccinated against common pathogens, leading to acquired pathogen-specific immunity with a robust memory T-cell repertoire. Although CD8
MeSH term(s)	Adenoviridae/genetics ; Adenoviridae/immunology ; Animals ; Antigens, Neoplasm/genetics ; Antigens, Neoplasm/immunology ; Antineoplastic Agents, Immunological/administration & dosage ; CD4-Positive T-Lymphocytes/immunology ; Cancer Vaccines/administration & dosage ; Cancer Vaccines/immunology ; Cell Line, Tumor/transplantation ; Diphtheria-Tetanus-Pertussis Vaccine/administration & dosage ; Diphtheria-Tetanus-Pertussis Vaccine/immunology ; Female ; Histocompatibility Antigens Class I/genetics ; Histocompatibility Antigens Class I/immunology ; Histocompatibility Antigens Class II/genetics ; Histocompatibility Antigens Class II/immunology ; Humans ; Immunologic Memory ; Immunotherapy/methods ; Melanoma, Experimental/immunology ; Melanoma, Experimental/pathology ; Melanoma, Experimental/therapy ; Mice ; Oncolytic Viruses/genetics ; Oncolytic Viruses/immunology ; Poliovirus Vaccine, Inactivated/administration & dosage ; Poliovirus Vaccine, Inactivated/immunology ; Programmed Cell Death 1 Receptor/antagonists & inhibitors ; Programmed Cell Death 1 Receptor/immunology ; T-Lymphocytes, Cytotoxic/immunology ; Vaccines, Combined/administration & dosage ; Vaccines, Combined/immunology
Chemical Substances	Antigens, Neoplasm ; Antineoplastic Agents, Immunological ; Cancer Vaccines ; DTPP vaccine ; Diphtheria-Tetanus-Pertussis Vaccine ; Histocompatibility Antigens Class I ; Histocompatibility Antigens Class II ; Pdcd1 protein, mouse ; Poliovirus Vaccine, Inactivated ; Programmed Cell Death 1 Receptor ; Vaccines, Combined
Language	English
Publishing date	2020-02-27
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1432-1
ISSN	1538-7445 ; 0008-5472
ISSN (online)	1538-7445
ISSN	0008-5472
DOI	10.1158/0008-5472.CAN-19-2062
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Article ; Online: Toxicological and bio-distribution profile of a GM-CSF-expressing, double-targeted, chimeric oncolytic adenovirus ONCOS-102 - Support for clinical studies on advanced cancer treatment.

Lukasz Kuryk / Lotta Vassilev / Tuuli Ranki / Akseli Hemminki / Aila Karioja-Kallio / Onerva Levälampi / Antti Vuolanto / Vincenzo Cerullo / Sari Pesonen

PLoS ONE, Vol 12, Iss 8, p e

2017 Volume 0182715

Abstract	The purpose of this work was to carry out preclinical toxicity and bio-distribution studies required for regulatory approval of a clinical trial application for Phase I clinical studies of ONCOS-102 (Ad5/3-D24-GM-CSF) for therapy of advanced cancers (NCT01598129). The study design, route of administration and dosage differs from the clinical protocol and in more detail, investigate bio-distribution and toxicological profile of ONCOS-102 treatment in animal model. The study was carried out in 300 hamsters divided into nine test groups-three bio-distribution groups and six groups for analysis of toxicity. Hamsters received ONCOS-102 by intracardial, intraperitoneal or subcutaneous injections. Additionally, one group was administered twice a week with intraperitoneal injections of Cyclophosphamide. The control animals were administered with NaCl solution without ONCOS-102 in the same volume and the same way. No adverse effects of repeated administration of ONCOS-102 including body weight, food consumption, hematology and clinical chemistry parameters, histopathology and bio-accumulation were observed in the course of 6-month administration and following 3- month recovery period. All obtained findings indicate the treatment clinically safe.
Keywords	Medicine ; R ; Science ; Q
Subject code	630
Language	English
Publishing date	2017-01-01T00:00:00Z
Publisher	Public Library of Science (PLoS)
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Synergistic anti-tumor efficacy of immunogenic adenovirus ONCOS-102 (Ad5/3-D24-GM-CSF) and standard of care chemotherapy in preclinical mesothelioma model.

Kuryk, Lukasz / Haavisto, Elina / Garofalo, Mariangela / Capasso, Cristian / Hirvinen, Mari / Pesonen, Sari / Ranki, Tuuli / Vassilev, Lotta / Cerullo, Vincenzo

International journal of cancer

2016 Volume 139, Issue 8, Page(s) 1883–1893

Abstract: Malignant mesothelioma (MM) is a rare cancer type caused mainly by asbestos exposure. The median overall survival time of a mesothelioma cancer patient is less than 1-year from diagnosis. Currently there are no curative treatment modalities for malignant ...

Abstract	Malignant mesothelioma (MM) is a rare cancer type caused mainly by asbestos exposure. The median overall survival time of a mesothelioma cancer patient is less than 1-year from diagnosis. Currently there are no curative treatment modalities for malignant mesothelioma, however treatments such as surgery, chemotherapy and radiotherapy can help to improve patient prognosis and increase life expectancy. Pemetrexed-Cisplatin is the only standard of care (SoC) chemotherapy for malignant mesothelioma, but the median PFS/OS (progression-free survival/overall survival) from the initiation of treatment is only up to 12 months. Therefore, new treatment strategies against malignant mesothelioma are in high demand. ONCOS-102 is a dual targeting, chimeric oncolytic adenovirus, coding for human GM-CSF. The safety and immune activating properties of ONCOS-102 have already been assessed in phase 1 study (NCT01598129). In this preclinical study, we evaluated the antineoplastic activity of combination treatment with SoC chemotherapy (Pemetrexed, Cisplatin, Carboplatin) and ONCOS-102 in xenograft BALB/c model of human malignant mesothelioma. We demonstrated that ONCOS-102 is able to induce immunogenic cell death of human mesothelioma cell lines in vitro and showed anti-tumor activity in the treatment of refractory H226 malignant pleural mesothelioma (MPM) xenograft model. While chemotherapy alone showed no anti-tumor activity in the mesothelioma mouse model, ONCOS-102 was able to slow down tumor growth. Interestingly, a synergistic anti-tumor effect was seen when ONCOS-102 was combined with chemotherapy regimens. These findings give a rationale for the clinical testing of ONCOS-102 in combination with first-line chemotherapy in patients suffering from malignant mesothelioma.
MeSH term(s)	Adenoviridae/genetics ; Adenoviridae/immunology ; Adenoviridae/physiology ; Animals ; Antineoplastic Combined Chemotherapy Protocols/pharmacology ; Carboplatin/administration & dosage ; Cell Line, Tumor ; Combined Modality Therapy ; Granulocyte-Macrophage Colony-Stimulating Factor/administration & dosage ; Granulocyte-Macrophage Colony-Stimulating Factor/genetics ; Granulocyte-Macrophage Colony-Stimulating Factor/immunology ; Humans ; Lung Neoplasms/drug therapy ; Lung Neoplasms/immunology ; Lung Neoplasms/therapy ; Lung Neoplasms/virology ; Mesothelioma/drug therapy ; Mesothelioma/immunology ; Mesothelioma/therapy ; Mesothelioma/virology ; Mesothelioma, Malignant ; Mice ; Mice, Inbred BALB C ; Oncolytic Virotherapy/methods ; Pemetrexed/administration & dosage ; Virus Replication ; Xenograft Model Antitumor Assays
Chemical Substances	Pemetrexed (04Q9AIZ7NO) ; Granulocyte-Macrophage Colony-Stimulating Factor (83869-56-1) ; Carboplatin (BG3F62OND5)
Language	English
Publishing date	2016-06-24
Publishing country	United States
Document type	Journal Article
ZDB-ID	218257-9
ISSN	1097-0215 ; 0020-7136
ISSN (online)	1097-0215
ISSN	0020-7136
DOI	10.1002/ijc.30228
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Zs.A 478: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (1.OG) ab Jg. 2022: Lesesaal (EG)
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Article: Systemic efficacy of oncolytic adenoviruses in imagable orthotopic models of hormone refractory metastatic breast cancer.

Ranki, Tuuli / Särkioja, Merja / Hakkarainen, Tanja / von Smitten, Karl / Kanerva, Anna / Hemminki, Akseli

International journal of cancer

2007 Volume 121, Issue 1, Page(s) 165–174

Abstract: Conditionally replicating oncolytic adenoviruses represent a promising developmental strategy for the treatment of cancer refractory to current treatments, such as hormone refractory metastatic breast cancer. In clinical cancer trials, adenoviral agents ... ...

Abstract	Conditionally replicating oncolytic adenoviruses represent a promising developmental strategy for the treatment of cancer refractory to current treatments, such as hormone refractory metastatic breast cancer. In clinical cancer trials, adenoviral agents have been well tolerated, but gene transfer has been insufficient for clinical benefit. One of the main reasons may be the deficiency of the primary adenovirus receptor, and therefore viral capsid modifications have been employed. Another obstacle to systemic delivery is rapid clearance of virus by hepatic Kupffer cells and subsequent inadequate bioavailability. In this study, we compared several capsid-modified oncolytic adenoviruses for the treatment of breast cancer with and without Kupffer cell inactivation. Replication deficient capsid-modified viruses were analyzed for their gene transfer efficacy in vitro in breast cancer cell lines and clinical samples and in vivo in orthotopic models of breast cancer. The effect of Kupffer cell depleting agents on gene transfer efficacy in vivo was evaluated. An aggressive lung metastatic model was developed to study the effect of capsid-modified oncolytic adenoviruses on survival. Capsid-modified viruses displayed increased gene transfer and cancer cell killing in vitro and resulted in increased survival in an orthotopic model of lung metastatic breast cancer in mice. Biodistribution of viruses was favorable, tumor burden and treatment response could be monitored repeatedly. Kuppfer cell inactivation led to enhanced systemic gene delivery, but did not increase the survival of mice. These results facilitate clinical translation of oncolytic adenoviruses for the treatment of hormone refractory metastatic breast cancer.
MeSH term(s)	Adenoviridae/pathogenicity ; Animals ; Breast Neoplasms/pathology ; Breast Neoplasms/therapy ; Breast Neoplasms/virology ; Capsid Proteins/genetics ; Capsid Proteins/metabolism ; Cell Line ; Disease Models, Animal ; Gadolinium ; Gene Transfer Techniques ; Hormones/metabolism ; Humans ; Liposomes ; Mice ; Neoplasm Metastasis/pathology ; Oncolytic Virotherapy ; Poly I ; Survival Rate ; Virus Replication ; Xenograft Model Antitumor Assays
Chemical Substances	Capsid Proteins ; Hormones ; Liposomes ; Poly I (25249-22-3) ; Gadolinium (AU0V1LM3JT)
Language	English
Publishing date	2007-07-01
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	218257-9
ISSN	1097-0215 ; 0020-7136
ISSN (online)	1097-0215
ISSN	0020-7136
DOI	10.1002/ijc.22627
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