Genomes and Genes
xenograft model antitumor assays
Summary: In vivo methods of screening investigative anticancer drugs, biologic response modifiers or radiotherapies. Human tumor tissue or cells are transplanted into mice or rats followed by tumor treatment regimens. A variety of outcomes are monitored to assess antitumor effectiveness.
- Van Linden A, Baturin D, Ford J, Fosmire S, Gardner L, Korch C, et al. Inhibition of Wee1 sensitizes cancer cells to antimetabolite chemotherapeutics in vitro and in vivo, independent of p53 functionality. Mol Cancer Ther. 2013;12:2675-84 pubmed publisher..These data provide preclinical justification for testing MK1775 and cytarabine in patients with leukemia. ..
- Lin D, Wyatt A, Xue H, Wang Y, Dong X, Haegert A, et al. High fidelity patient-derived xenografts for accelerating prostate cancer discovery and drug development. Cancer Res. 2014;74:1272-83 pubmed publisher..We predict that these next-generation models will be transformative for advancing mechanistic understanding of disease progression, response to therapy, and personalized oncology. ..
- Fernandez S, Robertson F, Pei J, Aburto Chumpitaz L, Mu Z, Chu K, et al. Inflammatory breast cancer (IBC): clues for targeted therapies. Breast Cancer Res Treat. 2013;140:23-33 pubmed publisher..Additionally, FC-IBC02 showed amplification of ALK and NOTCH3. These results indicate that MYC, ATAD2, CD44, NOTCH3, ALK and/or FAK1 may be used as potential targeted therapies against IBC. ..
- Yang C, Li Y, Wang Q, Huang K, Wei J, Wang Y, et al. EGFR/EGFRvIII remodels the cytoskeleton via epigenetic silencing of AJAP1 in glioma cells. Cancer Lett. 2017;403:119-127 pubmed publisher..These data suggest that activation of the EGFR signal transduction pathway genetically silences anti-oncogenes to enhance GBM malignancy. MK2206 might be a promising therapeutic for EGFR/EGFRvIII-positive GBMs. ..
- Juneja M, Kobelt D, Walther W, Voss C, Smith J, Specker E, et al. Statin and rottlerin small-molecule inhibitors restrict colon cancer progression and metastasis via MACC1. PLoS Biol. 2017;15:e2000784 pubmed publisher..This is-to the best of our knowledge-the first identification of inhibitors restricting cancer progression and metastasis via the novel target MACC1. This drug repositioning might be of therapeutic value for CRC patients. ..
- Zhuang Z, Xie N, Hu J, Yu P, Wang C, Hu X, et al. Interplay between Î”Np63 and miR-138-5p regulates growth, metastasis and stemness of oral squamous cell carcinoma. Oncotarget. 2017;8:21954-21973 pubmed publisher..Therefore, our data reveal that the interplay between Î”Np63 and miR-138-5p promotes OSCC progression by regulating cell growth, metastasis and stemness. ..
- Liu T, Zhao L, Hou H, Ding L, Chen W, Li X. Ginsenoside 20(S)-Rg3 suppresses ovarian cancer migration via hypoxia-inducible factor 1 alpha and nuclear factor-kappa B signals. Tumour Biol. 2017;39:1010428317692225 pubmed publisher..Taken together, our study suggests that 20(S)-Rg3 is a strong inhibitor of hypoxia-inducible factor 1?, which may provide a novel agent for future treatments for ovarian cancer. ..
- Edwards Z, Trotter E, Torres Ayuso P, Chapman P, Wood H, Nyswaner K, et al. Survival of Head and Neck Cancer Cells Relies upon LZK Kinase-Mediated Stabilization of Mutant p53. Cancer Res. 2017;77:4961-4972 pubmed publisher..Our results establish LZK as critical for maintaining expression of mutant stabilized p53. Cancer Res; 77(18); 4961-72. Â©2017 AACR. ..
- Courtois S, Durán R, Giraud J, Sifré E, Izotte J, Megraud F, et al. Metformin targets gastric cancer stem cells. Eur J Cancer. 2017;84:193-201 pubmed publisher..These results suggest that the use of metformin could represent an efficient strategy to inhibit tumour growth by targeting gastric CSCs. ..
- Qin H, Liu X, Li F, Miao L, Li T, Xu B, et al. PAD1 promotes epithelial-mesenchymal transition and metastasis in triple-negative breast cancer cells by regulating MEK1-ERK1/2-MMP2 signaling. Cancer Lett. 2017;409:30-41 pubmed publisher..These results also raise the possibility that PAD1 may function as an important new biomarker for TNBC tumors and suggest that PAD1-specific inhibitors could potentially be utilized to treat metastatic breast cancer. ..
- Lal P, Cerofolini L, D Agostino V, Zucal C, Fuccio C, Bonomo I, et al. Regulation of HuR structure and function by dihydrotanshinone-I. Nucleic Acids Res. 2017;45:9514-9527 pubmed publisher..In vivo, DHTS potently inhibited xenograft tumor growth in a HuR-dependent model without systemic toxicity. ..
- Shimizu T, Kamel W, Yamaguchi Iwai S, Fukuchi Y, Muto A, Saya H. Calcitriol exerts an anti-tumor effect in osteosarcoma by inducing the endoplasmic reticulum stress response. Cancer Sci. 2017;108:1793-1802 pubmed publisher..In addition, our results show that calcitriol could still be safely administered to osteosarcoma patients for its original purposes, including treatment of osteoporosis. ..
- Fu X, Wang X, Zhou S, Zhang Y. IONP-doped nanoparticles for highly effective NIR-controlled drug release and combination tumor therapy. Int J Nanomedicine. 2017;12:3751-3766 pubmed publisher..These results highlight the great potential of DOX-NPs in the treatment of cancer. ..
- Klinghammer K, Otto R, Raguse J, Albers A, Tinhofer I, Fichtner I, et al. Basal subtype is predictive for response to cetuximab treatment in patient-derived xenografts of squamous cell head and neck cancer. Int J Cancer. 2017;141:1215-1221 pubmed publisher..Activity of classical chemotherapies did not differ between the subtypes. In conclusion basal subtype was associated with response to EGFR directed therapy in head and neck squamous cell cancer patient-derived xenografts...
- Maynard J, Emmas S, Blé F, Barjat H, Lawrie E, Hancox U, et al. The use of 18F-Fluoro-deoxy-glucose positron emission tomography (18F-FDG PET) as a non-invasive pharmacodynamic biomarker to determine the minimally pharmacologically active dose of AZD8835, a novel PI3K? inhibitor. PLoS ONE. 2017;12:e0183048 pubmed publisher..The decrease in 18F-FDG uptake was dose dependent and data showed excellent PK/PD correlation. This data supports and parallels observations obtained with this class of compounds in patients. ..
- Marchan R, BÃ¼ttner B, Lambert J, Edlund K, Glaeser I, Blaszkewicz M, et al. Glycerol-3-phosphate Acyltransferase 1 Promotes Tumor Cell Migration and Poor Survival in Ovarian Carcinoma. Cancer Res. 2017;77:4589-4601 pubmed publisher..Overall, our findings show how GPAM influences intracellular LPA levels to promote cell migration and tumor growth. Cancer Res; 77(17); 4589-601. Â©2017 AACR. ..
- Saha K, Fisher M, Adhikary G, Grun D, Eckert R. Sulforaphane suppresses PRMT5/MEP50 function in epidermal squamous cell carcinoma leading to reduced tumor formation. Carcinogenesis. 2017;38:827-836 pubmed publisher..These studies suggest that the PRMT5/MEP50 is required for tumor growth and that reduced expression of this complex is a part of the mechanism of SFN suppression of tumor formation. ..
- Yoshida K, Toden S, Ravindranathan P, Han H, Goel A. Curcumin sensitizes pancreatic cancer cells to gemcitabine by attenuating PRC2 subunit EZH2, and the lncRNA PVT1 expression. Carcinogenesis. 2017;38:1036-1046 pubmed publisher..Overall, this study indicates clinical relevance for combining curcumin with chemotherapy to overcome chemoresistance in PDAC...
- Abou ElNaga A, Mutawa G, El Sherbiny I, Abd ElGhaffar H, Allam A, Ajarem J, et al. Novel Nano-Therapeutic Approach Actively Targets Human Ovarian Cancer Stem Cells after Xenograft into Nude Mice. Int J Mol Sci. 2017;18: pubmed publisher..A drug delivery system based on FA/PLGA NPs can enhance PTX's in vitro cytotoxicity and in vivo targeting potential against OCSCs. ..
- Liu Z, He K, Ma Q, Yu Q, Liu C, Ndege I, et al. Autophagy inhibitor facilitates gefitinib sensitivity in vitro and in vivo by activating mitochondrial apoptosis in triple negative breast cancer. PLoS ONE. 2017;12:e0177694 pubmed publisher..These results demonstrated that targeting autophagy should be considered as an effective therapeutic strategy to enhance the sensitivity of EGFR inhibitors on TNBC. ..
- Wang Y, Shen H, Yin Q, Zhang T, Liu Z, Zhang W, et al. Effect of NIMA-related kinase 2B on the sensitivity of breast cancer to paclitaxel in vitro and vivo. Tumour Biol. 2017;39:1010428317699754 pubmed publisher..Combination treatment using NIMA-related kinase 2B small interfering RNA and paclitaxel might be a novel potential therapy method for breast cancer. ..
- Li Y, Xiao M, Guo F. The role of Sox6 and Netrin-1 in ovarian cancer cell growth, invasiveness, and angiogenesis. Tumour Biol. 2017;39:1010428317705508 pubmed publisher..Moreover, our findings suggest a new role of SOX6 and netrin-1 for understanding the progression of ovarian cancer and have the potential for the development of new diagnosis and treatment strategies for ovarian cancer. ..
- Prall F, Maletzki C, Hühns M, Krohn M, Linnebacher M. Colorectal carcinoma tumour budding and podia formation in the xenograft microenvironment. PLoS ONE. 2017;12:e0186271 pubmed publisher..Dysregulation of wnt and BMP signalling appears to be transferred into the xenograft microenvironment, but not cytokine/chemokine signalling...
- Marostica L, de Barros A, Oliveira J, Salgado B, Cassali G, Leite E, et al. Antitumor effectiveness of a combined therapy with a new cucurbitacin B derivative and paclitaxel on a human lung cancer xenograft model. Toxicol Appl Pharmacol. 2017;329:272-281 pubmed publisher..These results corroborate our previous in vitro synergistic effects published. Taken together, these insights are novel and highlight the therapeutic potential of DACE and PTX combination scheme for NSCLC. ..
- Wang W, Xiao X, Chen X, Huo Y, Xi W, Lin Z, et al. Tumor-suppressive miR-145 co-repressed by TCF4-Î²-catenin and PRC2 complexes forms double-negative regulation loops with its negative regulators in colorectal cancer. Int J Cancer. 2018;142:308-321 pubmed publisher..Collectively, we elucidated the detailed molecular mechanism of how dysregulated Wnt/Î²-catenin signaling and tumor-suppressive miRNAs reciprocally regulate each other in CRC cells. ..
- Zhang X, Liu Z, Liu J, Zeng Y, Guo G, Sun Q. Antitumor activity of a Rhodococcus sp. Lut0910 isolated from polluted soil. Tumour Biol. 2017;39:1010428317711661 pubmed publisher..Our result would provide a new way and potent source for development of new anticancer agent from the polluted environment. ..
- Colín Val Z, González Puertos V, Mendoza Milla C, Gómez E, Huesca Gomez C, López Marure R. DHEA increases epithelial markers and decreases mesenchymal proteins in breast cancer cells and reduces xenograft growth. Toxicol Appl Pharmacol. 2017;333:26-34 pubmed publisher..In conclusion, DHEA could be useful in the treatment of breast cancer with mesenchymal phenotype. ..
- Zhao Z, Zhang G, Li W. Elevated Expression of ERCC6 Confers Resistance to 5-Fluorouracil and Is Associated with Poor Patient Survival in Colorectal Cancer. DNA Cell Biol. 2017;36:781-786 pubmed publisher..Therefore, this protein represents a novel therapeutic target for improvement of chemotherapeutic efficacy and predictive biomarker for patient survival. ..
- Wang Y, Zhou Y, Yang Z, Chen B, Huang W, Liu Y, et al. MiR-204/ZEB2 axis functions as key mediator for MALAT1-induced epithelial-mesenchymal transition in breast cancer. Tumour Biol. 2017;39:1010428317690998 pubmed publisher..ZEB2 was identified as a downstream target of miR-204 and MALAT1 exerted its function mainly through the miR-204/ZEB2 axis. Our findings suggested that MALAT1 may serve as a new diagnostic biomarker and therapy target for breast cancer. ..
- Zhan Y, Guo J, Yang W, Goncalves C, Rzymski T, Dreas A, et al. MNK1/2 inhibition limits oncogenicity and metastasis of KIT-mutant melanoma. J Clin Invest. 2017;127:4179-4192 pubmed publisher..Thus, our studies indicate that blocking MNK1/2 exerts potent antimelanoma effects and support blocking MNK1/2 as a potential strategy to treat patients positive for KIT mutations...
- Ahmad G, El Sadda R, Botchkina G, Ojima I, Egan J, Amiji M. Nanoemulsion formulation of a novel taxoid DHA-SBT-1214 inhibits prostate cancer stem cell-induced tumor growth. Cancer Lett. 2017;406:71-80 pubmed publisher..The results show that NE-DHA-SBT-1214 possesses significant activity against prostate CD133high/CD44+/high tumor-initiating cells both inÂ vitro and inÂ vivo. ..
- Belgiovine C, Bello E, Liguori M, Craparotta I, Mannarino L, Paracchini L, et al. Lurbinectedin reduces tumour-associated macrophages and the inflammatory tumour microenvironment in preclinical models. Br J Cancer. 2017;117:628-638 pubmed publisher..These peculiar effects, combined with its intrinsic activity against cancer cells, make lurbinectedin a compound of particular interest in oncology. ..
- Sangodkar J, Perl A, Tohme R, Kiselar J, Kastrinsky D, Zaware N, et al. Activation of tumor suppressor protein PP2A inhibits KRAS-driven tumor growth. J Clin Invest. 2017;127:2081-2090 pubmed publisher..Our strategy of reactivating endogenous PP2A may be applicable to the treatment of other diseases and represents an advancement toward the development of small molecule activators of tumor suppressor proteins. ..
- Zhou S, Liu F, Zhang A, Liang H, Wang Y, Ma R, et al. MicroRNA-199b-5p attenuates TGF-?1-induced epithelial-mesenchymal transition in hepatocellular carcinoma. Br J Cancer. 2017;117:233-244 pubmed publisher..Also, a positive regulatory loop exists between N-cadherin and Akt signalling represents a novel mechanism of TGF-?1-mediated EMT in HCC cells. ..
- Pedersen K, Bilal F, Bernadó Morales C, Salcedo M, Macarulla T, Massó Vallés D, et al. Pancreatic cancer heterogeneity and response to Mek inhibition. Oncogene. 2017;36:5639-5647 pubmed publisher..However, resistance because of intratumoral heterogeneity is likely to develop frequently, pointing to the necessity of identifying the factors and mechanisms of resistance to further develop this therapy. ..
- Li S, Dai W, Mo W, Li J, Feng J, Wu L, et al. By inhibiting PFKFB3, aspirin overcomes sorafenib resistance in hepatocellular carcinoma. Int J Cancer. 2017;141:2571-2584 pubmed publisher..Our results suggest that aspirin overcomes sorafenib resistance and their combination may be an effective treatment approach for HCC. ..
- Zhao Q, Deng X, Hong B, Wang F, Tang X, Yang Y, et al. Protein of Vascular Endothelial Growth Inhibitor 174 Inhibits Epithelial-Mesenchymal Transition in Renal Cell Carcinoma In Vivo. Anticancer Res. 2017;37:4269-4275 pubmed..Our findings indicate that VEGI174 prevents progression and tumor metastasis through inhibiting EMT in RCC in vivo. This may provide a new approach for the treatment of RCC. ..
- Ito S, Koso H, Sakamoto K, Watanabe S. RNA helicase DHX15 acts as a tumour suppressor in glioma. Br J Cancer. 2017;117:1349-1359 pubmed publisher..qPCR analysis revealed that DHX15 suppressed expression of NF-κB downstream target genes as well as the genes involved in splicing. These findings provide evidence that DHX15 acts as a tumour suppressor gene in glioma. ..
- Yamakawa Y, Tazawa H, Hasei J, Osaki S, Omori T, Sugiu K, et al. Role of zoledronic acid in oncolytic virotherapy: Promotion of antitumor effect and prevention of bone destruction. Cancer Sci. 2017;108:1870-1880 pubmed publisher..These results suggest that combination therapy of OBP-301 and ZOL suppresses osteosarcoma progression via suppression of MCL1 and osteoclast activation. ..
- Song Z, Wu P, Ni J, Liu T, Fan C, Bao Y, et al. Testes-specific protease 50 promotes cell proliferation via inhibiting activin signaling. Oncogene. 2017;36:5948-5957 pubmed publisher..Thus, our studies revealed a novel regulatory mechanism underlying TSP50-induced cell proliferation and provided a new favorable intervention target for the treatment of breast cancer. ..
- Xie C, He Y, Zhen M, Wang Y, Xu Y, Lou L. Puquitinib, a novel orally available PI3K? inhibitor, exhibits potent antitumor efficacy against acute myeloid leukemia. Cancer Sci. 2017;108:1476-1484 pubmed publisher..Thus, puquitinib is a promising agent with pharmacologic properties that are favorable for the treatment of AML. ..
- Naziroglu M, Ciğ B, Blum W, Vizler C, Buhala A, Marton A, et al. Targeting breast cancer cells by MRS1477, a positive allosteric modulator of TRPV1 channels. PLoS ONE. 2017;12:e0179950 pubmed publisher..p., injection twice a week). In conclusion, in view of a putative in vivo treatment with MRS1477 or similar compounds further optimization is required. ..
- Karpel Massler G, Ishida C, Bianchetti E, Shu C, Perez Lorenzo R, Horst B, et al. Inhibition of Mitochondrial Matrix Chaperones and Antiapoptotic Bcl-2 Family Proteins Empower Antitumor Therapeutic Responses. Cancer Res. 2017;77:3513-3526 pubmed publisher..Our results show how combining mitochondrial chaperone and Bcl-2 family inhibitors can synergize to safely degrade the growth of tumors recalcitrant to other treatments. Cancer Res; 77(13); 3513-26. ©2017 AACR. ..
- Yu W, Qu H, Cao G, Liu C, Deng H, Zhang Z. MtHsp70-CLIC1-pulsed dendritic cells enhance the immune response against ovarian cancer. Biochem Biophys Res Commun. 2017;494:13-19 pubmed publisher..These results indicate that DCs pulsed with MtHsp70-CLIC1 can enhance antitumor immunity against OC, providing a novel immune therapeutic strategy...