20 research outputs found
Gli1 enhances migration and invasion via up-regulation of MMP-11 and promotes metastasis in ERĪ± negative breast cancer cell lines
Gli1 is an established oncogene and its expression in Estrogen Receptor (ER) Ī± negative and triple negative breast cancers is predictive of a poor prognosis; however, the biological functions regulated by Gli1 in breast cancer have not been extensively evaluated. Herein, Gli1 was over-expressed or down-regulated (by RNA interference and by expression of the repressor form of Gli3) in the ERĪ± negative, human breast cancer cell lines MDA-MB-231 and SUM1315. Reduced expression of Gli1 in these two cell lines resulted in a decrease in migration and invasion. Gli1 over-expression increased the migration and invasion of MDA-MB-231 cells with a corresponding increase in expression of MMP-11. Silencing MMP-11 in MDA-MB-231 cells that over-expressed Gli1 abrogated the Gli1-induced enhancement of migration and invasion. Sustained suppression of Gli1 expression decreased growth of MDA-MB-231 in vitro by increasing apoptosis and decreasing proliferation. In addition, silencing of Gli1 reduced the numbers and sizes of pulmonary metastases of MDA-MB-231 in an in vivo experimental metastasis assay. In summary, Gli1 promotes the growth, survival, migration, invasion and metastasis of ERĪ± negative breast cancer. Additionally, MMP-11 is up-regulated by Gli1 and mediates the migration and invasion induced by Gli1 in MDA-MB-231
Peripheral giant cell granuloma recurring as an exclusively intra-osseous lesion: An unusual clinical presentation
Giant cell lesions of the jaws represent distinctive clinico-pathological spectrum. They manifest as peripheral and central lesions, occurring as solitary growths to involving multiple regions of the jaw. The present report presents a unique case of giant cell lesions of the jaws, wherein a peripheral giant cell granuloma recurred exclusively as a central giant cell lesion in a young patient. The recurrence was noted after a time-span of 3 years since the diagnosis and surgical excision of the peripheral lesion. Biochemical investigations were advised to rule out the possibility of hyperparathyroidism. Following a confirmed diagnosis of central giant cell granuloma, not associated with any other systemic conditions, an apt treatment plan was devised for an early rehabilitation of the patient
Breast Cancer Metastasis Suppressor 1 Up-regulates miR-146, Which Suppresses Breast Cancer Metastasis
Metastasis Research SocietyāAmerican Association for Cancer Research Joint Conference on Metastasis
Breast Cancer Metastasis Suppressor-1 Differentially Modulates Growth Factor Signaling*Sā
That metastatic tumor cells grow in selective non-native environments
suggests an ability to differentially respond to local microenvironments.
BRMS1, like other metastasis suppressors, halts ectopic growth (metastasis)
without blocking orthotopic tumor formation. BRMS1-expressing tumor cells
reach secondary sites but do not colonize distant tissues, compelling the
hypothesis that BRMS1 selectively restricts the ability of tumor cells to
respond to exogenous regulators in different tissues. Here we report that
BRMS1 expression in metastatic human breast cancer cells leads to a selective
reduction in epidermal growth factor receptor expression and downstream (AKT)
signaling. Signaling through another receptor tyrosine kinase, hepatocyte
growth factor receptor (c-Met), remains unaltered despite reduced levels of
the signaling intermediate phosphatidylinositol (4,5)-bisphosphate.
Interestingly, reduced downstream calcium signaling is observed following
treatment with platelet-derived growth factor, consistent with decreased
phosphatidylinositol (4,5)-bisphosphate. However, platelet-derived growth
factor receptor expression is unaltered. Thus, BRMS1 differentially attenuates
cellular responses to mitogenic signals, not only dependent upon the specific
signal received, but at varying steps within the same signaling cascade.
Specific modulation of signaling responses received from the microenvironment
may ultimately dictate which environments are permissive/restrictive for tumor
cell growth and provide insights into the biology underlying metastasis
Metastasis Research SocietyāAmerican Association for Cancer Research Joint Conference on Metastasis
The Volume of Three-Dimensional Cultures of Cancer Cells In Vitro Influences Transcriptional Profile Differences and Similarities with Monolayer Cultures and Xenografted Tumors
Improving the congruity of preclinical models with cancer as it is manifested in humans is a potential way to mitigate the high attrition rate of new cancer therapies in the clinic. In this regard, three-dimensional (3D) tumor cultures in vitro have recently regained interest as they have been acclaimed to have higher similarity to tumors in vivo than to cells grown in monolayers (2D). To identify cancer functions that are active in 3D rather than in 2D cultures, we compared the transcriptional profiles (TPs) of two non-small cell lung carcinoma cell lines, NCI-H1650 and EBC-1 grown in both conditions to the TP of xenografted tumors. Because confluence, diameter or volume can hypothetically alter TPs, we made intra- and inter-culture comparisons using samples with defined dimensions. As projected by Ingenuity Pathway Analysis (IPA), a limited number of signal transduction pathways operational in vivo were better represented by 3D than by 2D cultures in vitro. Growth of 2D and 3D cultures as well as xenografts induced major changes in the TPs of these 3 modes of culturing. Alterations of transcriptional network activation that were predicted to evolve similarly during progression of 3D cultures and xenografts involved the following functions: hypoxia, proliferation, cell cycle progression, angiogenesis, cell adhesion, and interleukin activation. Direct comparison of TPs of 3D cultures and xenografts to monolayer cultures yielded up-regulation of networks involved in hypoxia, TGF and Wnt signaling as well as regulation of epithelial mesenchymal transition. Differences in TP of 2D and 3D cancer cell cultures are subject to progression of the cultures. The emulation of the predicted cell functions in vivo is therefore not only determined by the type of culture in vitro but also by the confluence or diameter of the 2D or 3D cultures, respectively. Consequently, the successful implementation of 3D models will require phenotypic characterization to verify the relevance of applying these models for drug development
Large deflection model for nonlinear flexural vibration analysis of a highly flexible rotor-bearing system
Expression of the Breast Cancer Metastasis Suppressor 1 (BRMS1) maintains in vitro chemosensitivity of breast cancer cells
ABT-414, an Antibody-Drug Conjugate Targeting a Tumor-Selective EGFR Epitope.
Targeting tumor-overexpressed EGFR with an antibody-drug conjugate (ADC) is an attractive therapeutic strategy; however, normal tissue expression represents a significant toxicity risk. The anti-EGFR antibody ABT-806 targets a unique tumor-specific epitope and exhibits minimal reactivity to EGFR in normal tissue, suggesting its suitability for the development of an ADC. We describe the binding properties and preclinical activity of ABT-414, an ABT-806 monomethyl auristatin F conjugate. In vitro, ABT-414 selectively kills tumor cells overexpressing wild-type or mutant forms of EGFR. ABT-414 inhibits the growth of xenograft tumors with high EGFR expression and causes complete regressions and cures in the most sensitive models. Tumor growth inhibition is also observed in tumor models with EGFR mutations, including activating mutations and those with the exon 2-7 deletion [EGFR variant III (EGFRvIII)], commonly found in glioblastoma multiforme. ABT-414 exhibits potent cytotoxicity against glioblastoma multiforme patient-derived xenograft models expressing either wild-type EGFR or EGFRvIII, with sustained regressions and cures observed at clinically relevant doses. ABT-414 also combines with standard-of-care treatment of radiation and temozolomide, providing significant therapeutic benefit in a glioblastoma multiforme xenograft model. On the basis of these results, ABT-414 has advanced to phase I/II clinical trials, and objective responses have been observed in patients with both amplified wild-type and EGFRvIII-expressing tumors. Mol Cancer Ther; 15(4); 661-9. Ā©2016 AACR. Mol Cancer Ther 2016 Apr; 15(4): 661-