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Tumor Eradication (tumor + eradication)

Distribution by Scientific Domains

Medical Sciences	60%

Selected Abstracts

Antivascular Tumor Eradication by Hypericin-mediated Photodynamic Therapy,

PHOTOCHEMISTRY & PHOTOBIOLOGY, Issue 5 2002
Bin Chen
ABSTRACT Photodynamic therapy (PDT) with hypericin has been shown to inhibit tumor growth in different tumor models, and tumor vascular damage was suggested to be mainly responsible for the antitumoral effect. Here, we demonstrate tumor vascular damage and its consequence on local tumor control after hypericin-mediated PDT by using both short and long drug,light intervals. Radiation-induced fibrosarcoma-1 tumors were exposed to laser light at either 0.5 or 6 h after a 5 mg/kg dose of hypericin. Tumor perfusion was monitored by fluorescein dye,exclusion assay and by Hoechst 33342 staining of functional blood vessels. Significant reduction in tumor perfusion was found immediately after both PDT treatments. A complete arrest of vascular perfusion was detected by 15 h after the 0.5 h-interval PDT, whereas well-perfused areas could still be found at this time in tumors after the 6 h-interval PDT. A histological study confirmed that primary vascular damage was involved in both PDT treatments. Tumor cells appeared intact shortly after light treatment, degenerated at later hours and became extensively pycnotic at 24 h after the 0.5 h-interval PDT. PDT under this condition led to complete tumor cure. In contrast, significant numbers of viable tumor cells, especially at the tumor periphery, were found histologically at 24 h after the 6 h-interval PDT. No tumor cure was obtained when PDT was performed at this time. Our results strongly suggest that targeting the tumor vasculature by applying short drug,light interval PDT with hypericin might be a promising way to eradicate solid tumors. [source]

NF-,B in Photodynamic Therapy: Discrepancies of a Master Regulator

PHOTOCHEMISTRY & PHOTOBIOLOGY, Issue 5 2006
Jean-Yves Matroule
ABSTRACT Tumor eradication by photodynamic therapy (PDT) results from the onset of distinct killing processes. In addition to the well-known necrotic and apoptotic mechanisms, PDT initiates an inflammatory response that will indirectly contribute to tumor clearance. The NF-,B transcription factor is a major regulator of inflammation modulating the expression of cyto-kines, chemokines, and adhesion molecules in various cell types in response to a large number of stimuli. Besides, NF-,B regulates the expression of antiapoptotic genes, cyclooxygenases (COXs) and metalloproteinases (MMPs) as well, thereby favoring tumor cell proliferation and dissemination. In the present review, we aim to summarize the current knowledge on NF-,B status following photosensitization of cancer cells and endothelial cells. In order to unravel the NF-,B impact in PDT tumorigenicity and recurrences, we will stress the discrepancies of this major transcription factor relative to the signaling cascades underlying its activation and the cellular effects triggered by its translocation into the nucleus and its binding to its target genes. [source]

IFN-, withdrawal after immunotherapy potentiates B16 melanoma invasion and metastasis by intensifying tumor integrin ,v,3 signaling

INTERNATIONAL JOURNAL OF CANCER, Issue 3 2008
Wei Gong
Abstract Immunotherapy can effectively suppress tumor, yet complete tumor eradication occurs infrequently. The metastatic potential of remnant tumor cells after immunotherapy and the underlying mechanisms have not been fully elucidated. Here, we report that the termination of immunotherapy strikingly increases the metastatic potential of remnant melanoma. This is mainly due to the withdrawal of IFN-, after immunotherapy. The relief of IFN-, stress led to the increase of ,v,3 integrin expression in B16 cells, which increased the adhesion of B16 cells to fibrinogen, fibronectin and laminin. Through ,v,3 signaling, the activation of FAK, upregulation of cdc2, production of active MMP-2 and MMP-9 and actin polymerization were intensified in B16 cells stimulated with ECM molecules 24 h after the withdrawal of IFN-,. The i.v. injection of such tumor cells into mice resulted in more metastatic tumor nodes in lung and shortened the survival of mice. The pitfall of immunotherapy termination can be remedied by the administration of recombinant CBD-HepII polypeptide of fibronectin, which effectively inhibits ,v,3 signaling. These findings suggest that the risk of tumor metastasis can be increased after the termination of immunotherapy, due to the withdrawal of IFN-, and that targeting ,v,3 signaling pathway can improve the therapeutic effect of immunotherapeutic approaches by reducing such metastatic risk. © 2008 Wiley-Liss, Inc. [source]

Selective occlusion of tumor blood vessels by targeted delivery of an antibody-photosensitizer conjugate

INTERNATIONAL JOURNAL OF CANCER, Issue 7 2006
Monica Fabbrini
Abstract The irregular vasculature and high interstitial pressure of solid tumors hinder the delivery of cytotoxic agents to cancer cells. As a consequence, the doses of chemotherapy necessary to achieve complete tumor eradication are associated with unacceptably high toxicities. The selective thrombosis of tumor blood vessels has been postulated as an alternative avenue for combating cancer, depriving tumors of nutrients and oxygen and causing an avalanche of tumor cell deaths. The human antibody L19, specific to the EDB domain of fibronectin, a marker of angiogenesis, is capable of selective in vivo localization around tumor blood vessels and is thus a suitable agent for delivering toxic payloads to the tumor neovasculature. Here we show that a chemical conjugate of the L19 antibody with the photosensitizer bis(triethanolamine)Sn(IV) chlorin e6, after intravenous injection and irradiation with red light, caused an arrest of tumor growth in mice with subcutaneous tumors. By contrast, a photosensitizer conjugate obtained with an antibody of identical pharmacokinetic properties but irrelevant specificity did not exhibit a significant therapeutic effect. These results confirm that vascular targeting strategies, aimed at the selective occlusion/disruption of tumor blood vessels, have a significant anticancer therapeutic potential and encourage the use of antibody-photosensitizer conjugates for the therapy of superficial tumors and possibly other angiogenesis-related pathologies. © 2005 Wiley-Liss, Inc. [source]

Activation of ASC induces apoptosis or necrosis, depending on the cell type, and causes tumor eradication

CANCER SCIENCE, Issue 8 2010
Kou Motani
The adaptor protein ASC (also called TMS1) links certain NLR proteins (e.g., NLRC4, NLRP3) and caspases. It is involved in the chemosensitivity of tumor cells and inflammation. Here, we found that ASC activation using NLRC4 mimicry or an autoinflammatory disease-associated NLRP3 mutant induced necrosis in COLO205 colon adenocarcinoma cells, but induced caspase-8-dependent apoptosis in NUGC-4 stomach cancer cells. As the Fas ligand induced caspase-8-dependent apoptosis in COLO205 cells, caspase-8 was intact in this cell line. ASC-mediated necrosis was preceded by lysosomal leakage, and diminished by inhibitors for vacuolar H+ -ATPase, cathepsins, and calpains but not by inhibitors for caspase-8, or aspartic proteases, suggesting that lysosomes and certain proteases were involved in this process. Finally, growing tumors of transplanted human cancer cells in nude mice were eradicated by the activation of endogenous ASC in the tumor cells, irrespective of the form of cell death. Thus, ASC mediates distinct forms of cell death in different cell types, and is a promising target for cancer therapy. (Cancer Sci 2010) [source]