Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0598934 (tumor growth)
 58,965 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

N-nitrosomethylurea (NMU) given intravenously to rats at age 50 days induced mammary carcinomas in 89% of BUF/N, 73% of Sprague-Dawley, and 89% of F344 females. Latent periods were, respectively, 77, 86, and 94 days. Mortality was negligible. Biologic properties of NMU-induced tumors were tested in the BUF/N inbred strain. Before treatment, it reduced the number of tumors per rat but not the incidence; and after the tumor was established, castration arrested tumor growth or caused a temporary regression of the tumor. Metastases to bone marrow and spleen were constant, but they were rare to the liver and lungs. After the primary tumor was removed, metastases continued to grow but at a slower rate than the growth of the primary tumor. Almost all tumors were transplantable intraperitoneally and/or subcutaneously in the inguinal area of intact as well as ovariectomized and adrenalectomized rats. Transplanted tumors were able to metastasize as were primary tumors. Doubling times of NMU-induced primary and transplanted carcinomas were similar to 7 days. Cachexia ensued at the 5th week from the onset of the first tumor. When the tumor was larger than 15 g, hypercalcemia was usually observed. The treatment described appears to be the simplest method for inducing in rats a most nearly complete model for human mammary carcinomas.
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PMID:N-nitrosomethylurea as mammary gland carcinogen in rats. 111 23

Halichondrin B and homohalichondrin B are novel tubulin-interacting agents isolated from marine sponges. The in vivo antitumor activities of these compounds were examined in human tumor models in immunodeficient mice and rats. In nude mice, regression or pronounced delay of subcutaneous tumor growth was obtained with both halichondrins, at a maximum tolerable dose of 20 micrograms/kg Q2Dx5, in three of four vinblastine-sensitive tumors, including two melanomas and one osteosarcoma; one small-cell lung cancer line was resistant. The halichondrins as well as vinblastine showed only marginal activity against KM20L colon carcinoma xenografts. In a LOX melanoma lung colony formation assay in groups of six nude mice, all control animals were sacrificed because of respiratory symptoms 38 days after cell injection, and likewise one vinblastine-treated mouse after 53 days. All halichondrin-treated mice in the lung colony assay appeared healthy throughout an observation period of 112 days (p = 0.002). Upon necropsy all vinblastine-treated animals, and two of six mice in the halichondrin group, had macroscopic lung tumor colonies. In a nude rat model for LOX bone marrow metastases, the mean lifespan of untreated control animals was 15 days. Whereas vinblastine had only a marginal effect (17 days) in this model, halichondrin B prolonged the lifespan of the animals to 32 days, representing a significant (p = 0.0016) difference between the two compounds. In conclusion, the halichondrins, which comprise a subtype of tubulin-interactive anti-mitotic agents, showed distinct antitumor activity profiles in human tumor models, thereby encouraging their further preclinical development and possible clinical evaluation.
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PMID:Comparative antitumor activities of halichondrins and vinblastine against human tumor xenografts. 941 95

The development of novel anti-cancer strategies requires more sensitive and less invasive methods to detect and monitor in vivo minimal residual disease in cancer models. Bone marrow metastases are indirectly detected by radiography as osteolytic and/or osteosclerotic lesions. Marrow micrometastases elude radiographic detection and, therefore, more sensitive methods are needed for their direct identification. Injection of cancer cells into the left cardiac ventricle of mice closely mimics micrometastatic spread. When luciferase-transfected cells are used, whole-body bioluminescent reporter imaging can detect microscopic bone marrow metastases of approximately 0.5 mm(3) volume, a size below the limit in which tumors need to induce angiogenesis for further growth. This sensitivity translates into early detection of intramedullary tumor growth, preceding the appearance of a radiologically evident osteolysis by approximately 2 weeks. Bioluminescent reporter imaging also enables continuous monitoring in the same animal of growth kinetics for each metastatic site and guides end-point analyses specifically to the bones affected by metastatic growth. This model will accelerate the understanding of the molecular events in metastasis and the evaluation of novel therapies aiming at repressing initial stages of metastatic growth.
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PMID:Optical imaging of cancer metastasis to bone marrow: a mouse model of minimal residual disease. 1189 Dec 10

Neuroblastoma (NB) is an often fatal pediatric tumor of neural crest origin. We previously isolated NB tumor-initiating cells (NB TIC) from bone marrow metastases that resemble cancer stem cells and form metastatic NB in immunodeficient animals with as few as ten cells. To identify signaling pathways important for the survival and self-renewal of NB TICs and potential therapeutic targets, we screened a small molecule library of 143 protein kinase inhibitors, including 33 in clinical trials. Cytostatic or cytotoxic drugs were identified that targeted PI3K (phosphoinositide 3-kinase)/Akt, PKC (protein kinase C), Aurora, ErbB2, Trk, and Polo-like kinase 1 (PLK1). Treatment with PLK1 siRNA or low nanomolar concentrations of BI 2536 or BI 6727, PLK1 inhibitors in clinical trials for adult malignancies, were cytotoxic to TICs whereas only micromolar concentrations of the inhibitors were cytotoxic for normal pediatric neural stem cells. Furthermore, BI 2536 significantly inhibited TIC tumor growth in a therapeutic xenograft model, both as a single agent and in combination with irinotecan, an active agent for relapsed NB. Our findings identify candidate kinases that regulate TIC growth and survival and suggest that PLK1 inhibitors are an attractive candidate therapy for metastatic NB.
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PMID:Small molecule kinase inhibitor screen identifies polo-like kinase 1 as a target for neuroblastoma tumor-initiating cells. 2130 81