Journal: Cancer Immunology, Immunotherapy : CII

Article Title: Preexisting antitumor immunity augments the antitumor effects of chemotherapy

doi: 10.1007/s00262-013-1417-7

Figure Lengend Snippet: T cell immunity is critical for the efficacy of chemotherapy on immunogenic tumors but not on non-immunogenic tumors. a Comparison of responses to cyclophosphamide (Cy) by small immunogenic MCA207 tumors in normal (WT) or T cell receptor beta gene (Tcrb) knockout mice. Ten-day tumors in normal mice or 8-day tumors in Tcrb knockout mice with similar size were treated with Cy once i.p. NoRx represents untreated controls. Tcrb knockout mice had a significantly decreased response to Cy than control WT mice (p < 0.05). One of two experiments is shown. b Comparison of responses by small MCA207 tumors to doxorubicin (Dox), gemcitabine (Gem) in normal (WT) and Tcrb knockout mice. Similar sized tumors were injected intratumorally with indicated drugs once. The untreated controls are same as in a. One of two experiments is shown. Tcrb knockout mice responded less to both intratumoral Dox and Gem than WT control mice (p < 0.05). c Response by small MCA207 tumors to Cy i.p. and Dox intratumorally in normal (WT) mice or mice depleted of T cells at the time of chemotherapy. Ten-day tumors were treated with indicated drugs once. T cells were depleted using CD4 and CD8 antibodies at the time of chemotherapy and repeated once 1 week later. WT mice did better and responded better to treatment with intratumoral Dox and i.p. Cy than mice treated with antibodies to CD4 and Cd8 to delete T cells (p < 0.05). One of three similar experiments is shown. d Responses by large MCA207 tumors to Cy i.p. in normal (WT) and Tcrb knockout mice. Tumors at different times of establishment from normal (WT) and Tcrb knockout mice, but with similar sizes were treated with Cy once i.p. One of two similar experiments is shown. Large tumors in wild-type (WT) control mice responded significantly better to Cy treatment than those from Tcrb knockout mice (p < 0.01). e Reponses of 7-day established non-immunogenic Pan02 tumors to Dox in normal mice or mice depleted of T cells. f Response of 12-day established non-immunogenic B16 tumors to Cy in normal mice or mice depleted of T cells. Responses were measured by tumor size (length × width), and presented as the mean ± SEM of tumor sizes of indicated number of mice in each group. These two non-immunogenic tumors failed to respond to chemotherapy

Article Snippet: Liposomal doxorubicin (DOXIL ® , Tibotec Therapeutics) was diluted to 1 mg/ml in PBS, and 0.1 ml volume was injected intratumorally (i.t.) (for large tumors) or para-tumorally (for small tumors).

Techniques: Comparison, Knock-Out, Control, Injection

Journal: Pharmaceuticals

Article Title: DHDK, a Plant-Derived Natural Small Molecule, Protects Against Doxorubicin-Induced Cardiotoxicity via the PPARG-CPT1B-FAO Axis

doi: 10.3390/ph18111759

Figure Lengend Snippet: Integrated network toxicology analysis of DOX targets in cardiotoxicity and chronic disorders. CCK-8 results confirm that DHDK can alleviate cardiomyocyte damage caused by DOX ( a ), Venn diagram of DOX and potential targets of cardiotoxicity ( b ), Venn diagrams of DOX and cardiotoxicity, potential targets of cardiac aging ( c ), and Venn diagrams of potential targets of cardiotoxicity caused by DOX and cardiac aging and lipid metabolism ( d ). Protein–protein Interaction (PPI) plot ( e ), Gene Ontology (GO) results ( f – h ), and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis ( i ) results of DOX-induced cardiotoxicity and cardiac aging. Data are presented as mean ± SD ( n = 3). Statistical significance was determined by Student’s t -test. * p < 0.05, ** p < 0.01, *** p < 0.001, **** p < 0.0001, ns indicated no statistical significance.

Article Snippet: Complementary toxicity prediction using ProTox-3.0 corroborated lipid metabolism disruption and membrane structural damage as primary mechanisms of DOX cardiotoxicity, shown in .

Techniques: CCK-8 Assay

Journal: Pharmaceuticals

Article Title: DHDK, a Plant-Derived Natural Small Molecule, Protects Against Doxorubicin-Induced Cardiotoxicity via the PPARG-CPT1B-FAO Axis

doi: 10.3390/ph18111759

Figure Lengend Snippet: Integrated network toxicology-pharmacology analysis revealing PPARG as a convergent potential target in DOX-induced cardiotoxicity and DHDK-mediated cardioprotection. Venn diagram ( a ), PPI plot ( b – d ), GO enrichment analysis ( e ), and KEGG pathway enrichment analysis ( f ) of DHDK alleviation of DOX in cardiotoxicity and cardiac aging. Non-covalent molecular docking results ( g ) and covalent molecular docking results ( h ) of DHDK and PPARG, a potential alleviation of DOX-induced cardiac injury. The expression level of the potential target protein PPARG was obtained in the Gene Expression Omnibus (GEO) database before and after DOX-induced cardiac injury ( i ).

Article Snippet: Complementary toxicity prediction using ProTox-3.0 corroborated lipid metabolism disruption and membrane structural damage as primary mechanisms of DOX cardiotoxicity, shown in .

Techniques: Expressing, Gene Expression