A5083452456- TGF-β signaling in diseases
- Cancer Cells and Metastasis
- Cellular Mechanics and Interactions
- Bone and Dental Protein Studies
- Cell Adhesion Molecules Research
- Wound Healing and Treatments
- 3D Printing in Biomedical Research
- Cell Image Analysis Techniques
- Periodontal Regeneration and Treatments
- Mitochondrial Function and Pathology
- Cancer Research and Treatments
- Genetic factors in colorectal cancer
- Cancer, Stress, Anesthesia, and Immune Response
- Cancer Genomics and Diagnostics
- Bone Metabolism and Diseases
- RNA modifications and cancer
- Mathematical Biology Tumor Growth
- RNA Research and Splicing
- Cancer-related gene regulation
- Pancreatic and Hepatic Oncology Research
- Laser Applications in Dentistry and Medicine
- Cancer-related molecular mechanisms research
- Fibroblast Growth Factor Research
- AI in cancer detection
- Sphingolipid Metabolism and Signaling
National Cancer Institute
2014-2024
Center for Cancer Research
2012-2024
National Institutes of Health
2008-2023
National Cancer Institute
2006-2023
Clinical Research Consortium
2022
ORCID
2010-2017
Bethesda University
2014
North Carolina Central University
2012
National Institutes of Health Clinical Center
2011
Cancer Genetics (United States)
2008
Extracellular matrix glycoproteins and proteoglycans bind a variety of growth factors cytokines thereby regulating assembly as well bone formation. However, little is known about the mechanisms by which extracellular molecules modulate osteogenic stem cells Using mice deficient in two members small leucine-rich proteoglycans, biglycan decorin, we uncovered role for these modulating formation from marrow stromal cells. Our studies showed that absence critical transforming factor-β...
We used 2D-cocultures employing fibroblasts of different genetic backgrounds and MCF10A-derived human breast epithelial cells increasingly malignant potential to investigate tumor-stroma interactions in cancer identify possible signaling pathways involved. Tumor induced expression matrix-metalloproteinase 9 (MMP-9) a pattern dependent on the degree their malignancy. In-situ zymography localized main gelatinolytic activity around stromal cocultures xenografted tumors. Use Smad3 knockout...
Overexpression of transforming growth factor beta (TGF-beta) is frequently associated with metastasis and poor prognosis, TGF-beta antagonism has been shown to prevent in preclinical models surprisingly little toxicity. Here, we have used the transplantable 4T1 model metastatic breast cancer address underlying mechanisms. We showed that efficacy anti-TGF-beta antibody 1D11 suppressing was dependent on a synergistic combination effects both tumor parenchyma microenvironment. The main outcome...
It has been reported that retinoic acid (RA) enhances regulatory T (T reg) cell conversion by inhibiting the secretion of cytokines interfere with conversion. This report shows these conclusions provide a partial explanation at best. First, RA not only interfered cytokine but also ability to inhibit reg naive cells. Furthermore, enhanced even in absence inhibitory cytokines. The latter effect depended on receptor α (RARα) did require Smad3, despite fact Smad3 expression. RARα1 isoform was...
Transforming growth factor β (TGFβ) is important in inflammation, angiogenesis, reepithelialization and connective tissue regeneration during wound healing. We analyzed components of TGFβ signaling pathway biopsies from 10 patients with nonhealing venous ulcers (VUs). Using comparative genomics transcriptional profiles VUs TGFβ-treated keratinocytes, we found deregulation target genes VUs. quantitative polymerase chain reaction (qPCR) immunohistochemical analysis, suppression TGFβRI, TGFβRII...
We report a novel mechanism of action ONC201 as mitochondria-targeting drug in cancer cells. was originally identified small molecule that induces transcription TNF-related apoptosis-inducing ligand (TRAIL) and subsequently kills cells by activating TRAIL death receptors. In this study, we examined toxicity on multiple human breast endometrial cell lines. attenuated viability all lines tested. Unexpectedly, not dependent either receptors nor caspases. Time-lapse live imaging revealed...
Carcinoma are complex societies of mutually interacting cells in which there is a progressive failure normal homeostatic mechanisms, causing the parenchymal component to expand inappropriately and ultimately disseminate distant sites. When cancer cell metastasizes, it first will be exposed associated fibroblasts immediate tumor microenvironment then as traverses underlying connective tissue towards bloodstream. The interaction with stromal influences biology by mechanisms that not yet fully...
Abstract Tumor stem cells or cancer initiating (CICs) are single tumor that can regenerate a metastasis. The identification and isolation of CICs remain challenging, variety putative CIC markers have been described. We hypothesized cell lines the NCI60 panel contain express markers. investigated expression surface (CD15, CD24, CD44, CD133, CD166, CD326, PgP) activity aldehyde dehydrogenase in singly combination by six-color fluorescence-activated sorting analysis. All were expressed panel....
Abstract Transforming growth factor βs (TGF-β) play a dual role in carcinogenesis, functioning as tumor suppressors early the process, and then switching to act prometastatic factors late-stage disease. We have previously shown that high molecular weight TGF-β antagonists can suppress metastasis without predicted toxicities. To address underlying mechanisms, we used 4T1 syngeneic mouse model of metastatic breast cancer. Treatment mice with monoclonal anti-TGF-β antibody (1D11) significantly...
Many cell lines currently used in medical research, such as cancer cells or stem cells, grow confluent sheets colonies. The biology of individual provide valuable information, thus the separation touching these microscopy images is critical for counting, identification and measurement cells. Over-segmentation single continues to be a major problem methods based on morphological watershed due high level noise images. There need new segmentation method that robust over wide variety biological...
Cancer cells alter their migratory properties during tumor progression to invade surrounding tissues and metastasize distant sites. However, it remains unclear how behaviors differ between of different malignancy whether these can be utilized assess the malignant potential cells. Here, we analyzed cell lines representing stages breast cancer using conventional migration assays or time-lapse imaging particle image velocimetry (PIV) capture dynamics. We find that number migrating in transwell...
Abstract The role of transforming growth factor β (TGF-β) in carcinogenesis is complex, with tumor suppressor and pro-oncogenic activities depending on the particular cell its stage malignant progression. We previously have demonstrated breast cancer lines that Smad2/3 signaling played a dominant mediating effects well-differentiated grown as xenografts prometastatic more invasive, metastatic line. Our present data based selective interference activation endogenous Smad2 Smad3 by stable...
The loss of TGFβ or its downstream mediator, Smad3, key players in tissue repair, accelerates closure incisional wounds mice. In contrast, we now report that excisional ear mice lacking Smad3 enlarge compared with wild-type controls resulting from changes extracellular matrix molecules, which alter the mechanotransduction properties these wounds. Specifically, levels elastin and glycosoaminoglycans are increased, collagen fibers more compactly organized, modulators like integrins, TGFβ1,...
Abstract We investigated the influence of acute wounding on tumor growth in a syngeneic mouse breast cancer model. Metastatic cells (4T1) were orthotopically injected into mammary fat pads BALB/c mice, and animals wounded locally by full thickness dermal incisions above or remotely scapula 9 days later. Local, but not remote, increased size when compared with sham treatment. Injection wound fluid close to site growth, whereas vitro serum proliferation rate 4T1 cells. Our results show that...
Exogenous administration of tumor necrosis factor‐α has been shown to both enhance and attenuate cutaneous healing in a dose‐dependent manner. We examined the effects factor inhibition wound by systemic local factor‐binding protein. Male Balb/C mice underwent dorsal skin incision with subcutaneous implantation 20 mg polyvinyl alcohol sponges (4 per animal). In Experiment I, one group ( n = 20) received intraperitoneal injections protein (3 mg/kg) at time wounding, while another saline. Four...
Abstract Background Although transforming growth factor β (TGF-β) typically inhibits proliferation of epithelial cells, consistent with a tumor suppressor activity, it paradoxically also exhibits pro-metastatic activity in the later stages carcinogenesis. Since tumors often display altered TGF-β signaling, particularly involving Smad-pathway, we investigated role Smad4-expression breast cancer. Methods Smad4 expression was by immunohistochemistry formalin-fixed, paraffin-embedded tissue from...
Macrophages comprise an essential component of the mammary microenvironment necessary for normal gland development. However, there is no viable in vivo model to study their role human breast function. We hypothesized that adding primary macrophages murine would enhance and provide a novel approach examine immune-stromal cell interactions during humanization process.Primary macrophages, presence or absence ectopic estrogen stimulation, were used humanize mouse glands. Mechanisms enhanced...