Monitoring TGFβ signaling in irradiated tumors.

Transforming growth factor β (TGFβ) is exquisitely regulated under physiological conditions but its activity is highly dysregulated in cancer. All cells make TGFβ and have receptors for the ligand, which is sequestered in the extracellular matrix in a latent form. Ionizing radiation elicits rapid release of TGFβ from these stores, so-called activation, over a wide range of doses and exposures, including low dose (<1Gy) whole-body irradiation, creating an extraordinarily potent signal in the irradiated tissue or tumor.

Inflammation Mediates the Development of Aggressive Breast Cancer Following Radiotherapy.

Purpose: Women treated with radiotherapy before 30 years of age have increased risk of developing breast cancer at an early age. Here, we sought to investigate mechanisms by which radiation promotes aggressive cancer.

Experimental Design: The tumor microenvironment (TME) of breast cancers arising in women treated with radiotherapy for Hodgkin lymphoma was compared with that of sporadic breast cancers.

Positron Emission Tomography Imaging of Functional Transforming Growth Factor β (TGFβ) Activity and Benefit of TGFβ Inhibition in Irradiated Intracranial Tumors.

Purpose: Transforming growth factor β (TGFβ) promotes cell survival by endorsing DNA damage repair and mediates an immunosuppressive tumor microenvironment. Thus, TGFβ activation in response to radiation therapy is potentially targetable because it opposes therapeutic control. Strategies to assess this potential in the clinic are needed.

Lack of radiation dose or quality dependence of epithelial-to-mesenchymal transition (EMT) mediated by transforming growth factor β.

Purpose: Epithelial-to-mesenchymal transition (EMT) is a phenotype that alters cell morphology, disrupts morphogenesis, and increases motility. Our prior studies have shown that the progeny of human mammary epithelial cells (HMECs) irradiated with 2 Gy undergoes transforming growth factor β (TGF-β)-mediated EMT. In this study we determined whether radiation dose or quality affected TGF-β-mediated EMT.

DNA polyplexes formed using PEGylated biodegradable hyperbranched polymers.

A novel PEGylated biodegradable hyperbranched PEG-b-PDMAEMA has been synthesized. The low toxicity, small molecular weight PDMAEMA chains were crosslinked using a biodegradable disulfide-based dimethacrylate (DSDMA) agent to yield higher molecular weight hyperbranched polymers. PEG chains were linked onto the polymer surface, masking the positive charge (as shown by Zeta potential measurements) and reducing the toxicity of the polymer.

Ionizing radiation predisposes nonmalignant human mammary epithelial cells to undergo transforming growth factor beta induced epithelial to mesenchymal transition.

Transforming growth factor beta1 (TGFbeta) is a tumor suppressor during the initial stage of tumorigenesis, but it can switch to a tumor promoter during neoplastic progression. Ionizing radiation (IR), both a carcinogen and a therapeutic agent, induces TGFbeta activation in vivo. We now show that IR sensitizes human mammary epithelial cells (HMEC) to undergo TGFbeta-mediated epithelial to mesenchymal transition (EMT).

Access to primary care for Medicare beneficiaries.

Objectives: To determine the acceptance rate of new Medicare patients by all primary care physicians. Among primary care physicians accepting new patients, to determine whether demographic and geographic factors are associated with the likelihood of accepting new Medicare patients.

Design: Cross-sectional.

Perceptions of physicians on the barriers and facilitators to integrating fall risk evaluation and management into practice.

Background: Falls are common, treatable, and result in considerable morbidity in older adults. However, fall risk factor evaluation and management targeted at high-risk patients is largely neglected in clinical practice.

Objective: To identify barriers and facilitators to the implementation of fall risk management by primary care providers.

Intensity-modulated radiation therapy in head and neck cancers: dosimetric advantages and update of clinical results.

Intensity-modulated radiation therapy (IMRT) is an exciting new modality in radiation therapy. The head and neck region is an ideal target for this new technology for several reasons. First, IMRT offers the potential for improved tumor control through delivery of high doses to the target volume.

Intensity-modulated radiation therapy for head and neck cancer.

Radiotherapy planning studies have confirmed dosimetric advantages of intensity-modulated radiation therapy over conventional and conformal radiation therapy. Utilization of intensity-modulated radiation therapy is ideal in head and neck cancer patients. Critical structures can be spared due to sharp dose gradients and limited organ motion with correct immobilization.

In situ analyses of genome instability in breast cancer.

Transition through telomere crisis is thought to be a crucial event in the development of most breast carcinomas. Our goal in this study was to determine where this occurs in the context of histologically defined breast cancer progression. To this end, we assessed genome instability (using fluorescence in situ hybridization) and other features associated with telomere crisis in normal ductal epithelium, usual ductal hyperplasia, ductal carcinoma in situ and invasive cancer.