CD200 Immune-Checkpoint Peptide Elicits an Anti-glioma Response Through the DAP10 Signaling Pathway.

Numerous therapies aimed at driving an effective anti-glioma response have been employed over the last decade; nevertheless, survival outcomes for patients remain dismal. This may be due to the expression of immune-checkpoint ligands such as PD-L1 by glioblastoma (GBM) cells which interact with their respective receptors on tumor-infiltrating effector T cells curtailing the activation of anti-GBM CD8 T cell-mediated responses. Therefore, a combinatorial regimen to abolish immunosuppression would provide a powerful therapeutic approach against GBM.

Antigen-specific culture of memory-like CD8 T cells for adoptive immunotherapy.

Cytotoxic T cells typically are expanded ex vivo in culture with IL2 for adoptive immunotherapy. This culture period leads to a differentiated phenotype and acquisition of effector function, as well as a loss of in vivo proliferative capability and antitumor efficacy. Here, we report antigen-specific and polyclonal expansion of cytotoxic T cells in a cocktail of cytokines and small molecules that leads to a memory-like phenotype in mouse and human cells even during extended culture, leading to enhanced in vivo expansion and tumor control in mice.

Profound impairment of adaptive immune responses by alkylating chemotherapy.

Overall, cancer vaccines have had a record of failure as an adjuvant therapy for malignancies that are treated with alkylating chemotherapy, and the contribution of standard treatment to that failure remains unclear. Vaccines aim to harness the proliferative potential of the immune system by expanding a small number of tumor-specific lymphocytes into a large number of antitumor effectors. Clinical trials are often conducted after treatment with alkylating chemotherapy, given either as standard therapy or for immunomodulatory effect.

Immunotoxin targeting CD133(+) breast carcinoma cells.

CD133 expression enriches for tumor-initiating cells and is a negative prognostic factor in numerous cancers. We previously developed an immunotoxin against CD133 by fusing a gene fragment encoding the scFv portion of an anti-CD133 antibody to a gene fragment encoding deimmunized PE38KDEL. The resulting fusion protein, dCD133KDEL, demonstrated potent antitumor activity following intratumoral delivery into head neck cell carcinoma xenografts.

Identification and characterization of a novel scFv recognizing human and mouse CD133.

CD133, also known as Prominin-1, is expressed on stem cells present in many tissues and tumors. In this work, we have identified and characterized a single-chain variable fragment (scFv) for the efficient and specific recognition of CD133. Phage display was used to develop the scFv from a previously reported anti-CD133 hybridoma clone 7, which was capable of recognizing both glycosylated and non-glycosylated forms of human CD133.

Active efflux of Dasatinib from the brain limits efficacy against murine glioblastoma: broad implications for the clinical use of molecularly targeted agents.

The importance of the blood-brain barrier in preventing effective pharmacotherapy of glioblastoma has been controversial. The controversy stems from the fact that vascular endothelial cell tight junctions are disrupted in the tumor, allowing some systemic drug delivery. P-glycoprotein (Pgp) and breast cancer resistance protein (BCRP) efflux drugs from brain capillary endothelial cells into the blood.

Superior efficacy of tumor cell vaccines grown in physiologic oxygen.

Purpose: Atmospheric oxygen (∼20% O(2)) has been the universal condition employed to culture tumor cells used as vaccine antigen. We tested the hypothesis that reducing oxygen tension would increase the efficacy of tumor cell lysate vaccines.

Experimental Design: GL261 glioma cells and EMT6 breast carcinoma cells were grown in 5% or 20% O(2).

The Missouri interpretation & translation survey: a pilot study of limited English proficiency.

A pilot study was developed and sent to health care stakeholders in Missouri; sixty-two surveys from a variety of providers and health care settings were analyzed. This preliminary survey suggests that more than a third of health care providers in Missouri routinely offer interpretation services, mostly by using paid phone service. At least 20%, however, do not offer interpreter services or the service is inadequate to properly convey pertinent health information.

Medication safety teams' guided implementation of electronic medication administration records in five nursing homes.

Background: The 1.6 million nursing home residents in the United States are at high risk for adverse effects from medication errors. In an attempt to decrease medication errors and improve safety practices, from 2003 through 2007 the study investigators partnered with five Midwestern nursing homes in implementing electronic point-of-care medication administration records (eMARs) and focused quality improvement (QI) efforts.

Barriers to safe medication administration in the nursing home--exploring staff perceptions and concerns about the medication use process.

The purpose of this study was to explore staff perceptions and concerns about the medication use process in the nursing home setting. A total of 76 staff members from 5 nursing homes in 3 Midwestern states participated in key informant interviews and focus groups. Common themes included issues related to communication, competing demands, and the challenges of a paper-based medication administration record.

Nursing home error and level of staff credentials.

Providing safe nursing home care is both a clinical and fiscal challenge in many countries. The fiscal realities result in the addition of other workers, such as medication technicians or aides (CMT/A), to the health care team. The purpose of this study was to determine the impact of various levels of credentialing among nursing home staff who deliver medications (RN, LPN, or CMT/A) on medication error.

Moving from a culture of blame to a culture of safety in the nursing home setting.

Topic: A culture of safety.

Purpose: To explore the current culture of blame and what organizational elements must be impacted to move toward a culture of safety in the nursing home setting.

Methods: A mixed-method approach incorporating a case study and staff member survey results were used to explicate the organizational elements impacting the current nursing home culture.

Condensed chromatin and cell inactivation by single-hit kinetics.

Mammalian cells are extremely sensitive to gamma rays at mitosis, the time at which their chromatin is maximally condensed. The radiation-induced killing of mitotic cells is well described by single-hit inactivation kinetics. To investigate if radiation hypersensitivity by single-hit inactivation correlated with chromatin condensation, Chinese hamster ovary (CHO) K1 (wild-type) and xrs-5 (radiosensitive mutant) cells were synchronized by mitotic shake-off procedures and the densities of their chromatin cross sections and their radiosensitivities were measured immediately and 2 h into G1 phase.

Radiation fields backscattered from material interfaces: I. Biological effectiveness.

Confluent cultures of CHO-K1 and CHO-xrs5 cells were irradiated attached to 6 microm Mylar with 137Cs gamma rays and 200 kVp X rays adjacent to scattering materials consisting of polystyrene, glass, aluminum, copper, tin and lead. The absorbed dose in cell nuclei was estimated from measurements of backscattered dose made with a parallel-plate ion chamber with a 5-microm Mylar window and a gas volume whose thickness was equivalent to approximately 2.6 microm of cells or tissue.

Microdosimetric single event spectra of Ytterbium-169 compared with commonly used brachytherapy sources and teletherapy beams.

Ytterbium-169 has been developed as a possible replacement for Iridium-192 and Iodine-125. The Theory of Dual Radiation Action predicts that the initial slope of the cell survival curve and therefore the relative biological effect at low dose rate is proportional to dose average lineal energy, yd, which is the microscopic analog of the dose average linear energy transferred. The quality factor used in radiation protection has been shown to be a function of the frequency average lineal energy, yf.

Calculated risk of breast cancer following mantle irradiation determined by measured dose.

Tumor registry data indicate a two- to fourfold increased incidence of breast cancer following mantle irradiation, but cumulative risk is unknown. Radiation exposure to the breasts underlying the mantle block ranges from 4 to 40 Gy and is dependent on relative positions of the breasts and mantle block. Unshielded outer breast quadrants near axillary nodal regions receive 36 to 40 Gy, while central breast quadrants under the lung blocks receive approximately 4 Gy as determined by dose volume histogram analysis.

Is the dose-response relationship for local control of Hodgkin's disease obscured by lung inhomogeneity corrections?

Absence of a dose-response relationship has been reported for local control of Hodgkin's disease between 30 and 42 Gy delivered to the mantle field in definitive irradiation. These dose ranges were determined at the central ray using irregular field (IF) calculations without benefit of dosimetric correction for lung inhomogeneity. Detailed analysis was performed of dose delivered to hilar and mediastinal regions with mantle field irradiation incorporating lung inhomogeneity corrections for the indicated dose ranges using 60Co and 6 MV linear accelerator.

Dosimetry of the breast for determining carcinogenic risk in mantle irradiation.

Development of secondary malignancies following treatment of Hodgkin's disease with radiation (central axis midline dose of 3600-4500 cGy) is a recognized risk, and the incidence in breast cancer has been reported to increase by a factor of 4.3 (95% confidence level 2.0 to 8.

Measurement of skin dose in primary irradiation of maxillary sinus carcinoma.

Subcutaneous involvement frequently occurs in maxillary sinus carcinoma. Radical resection does not include removal of the skin at risk. In standard postoperative wedge-pair treatment plans, the surface dose is dependent upon beam weighting, beam energy, and patient contour.

Comparison of dose distribution by means of bolus versus water bath phantom techniques in treatment of cutaneous sarcoma of an extremity.

Cutaneous involvement by Kaposi's sarcoma (KS) is frequently diffuse, requiring large field irradiation. Selective tissue compensation techniques, accomplished with either a 1.5 cm bolus cast or water bath phantom, are compared.

Microdosimetric single-event spectra for megavoltage electrons.

Experimental techniques have been developed for obtaining single-event microdosimetric spectra from hospital based linear accelerators. Therapeutic electrons of 12, 15, 18, and 20 MeV from Clinic 18 and 20 accelerators have been produced at ultralow dose rates. Details of the experimental methods have been described previously by the authors.

Small cell undifferentiated carcinoma of the maxillary sinus: technical considerations for radiation therapy.

Treatment principles for extrapulmonary small cell undifferentiated carcinoma follow those established for primary lung presentations including systemic chemotherapy and prophylactic cranial irradiation. Radiation of carcinoma involving the maxillary sinus includes lateral and anterior portals which exit through the brain. Presented is a treatment strategy used for postoperative radiation of small cell undifferentiated carcinoma of the maxillary sinus in conjunction with prophylactic cranial irradiation.