Patient/Family Education for Newly Diagnosed Pediatric Oncology Patients.

There is a paucity of data to support evidence-based practices in the provision of patient/family education in the context of a new childhood cancer diagnosis. Since the majority of children with cancer are treated on pediatric oncology clinical trials, lack of effective patient/family education has the potential to negatively affect both patient and clinical trial outcomes. The Children's Oncology Group Nursing Discipline convened an interprofessional expert panel from within and beyond pediatric oncology to review available and emerging evidence and develop expert consensus recommendations regarding harmonization of patient/family education practices for newly diagnosed pediatric oncology patients across institutions.

Autophagic flux in glioblastoma cells.

To establish metabolic context for radiation sensitivity by measuring autophagic flux in two different glioblastoma (GBM) cell lines. Clonogenic survival curve analysis of U87 or U251 cells exposed to γ radiation, fast neutrons, a mixed energy neutron beam (METNB) or Auger electrons from a gadolinium neutron capture (GdNC) reaction suggested other factors, beyond a defective DNA damage response, contribute to cell death of U251 cells. Altered tumor metabolism (autophagy) was hypothesized as a factor in U251 cells' clonogenic response.

Necrosis is not induced by gadolinium neutron capture in glioblastoma multiforme cells.

Purpose: A comparative study of the effects of different radiation modalities on cell death was performed.

Materials And Methods: Radiation modalities included γ-rays, fast neutrons, a mixed energy neutron beam called the modified enhanced thermal neutron beam and the mixed beam including Auger electron irradiation by gadolinium neutron capture. U87 (human brain tumor cells) cell survival curve data were modeled to predict how cells died.

Molecular and cellular effects of Auger emitters: 2008-2011.

Purpose: To review recent Auger emitter research with an emphasis on a review of findings on targeting and accumulation of Auger emitters in tumor cells.

Conclusion: Significant progress can be reported for targeting methods and improvements in methods to accumulate Auger emitters in the target cells, as well as advances in dose calculations. These studies further our understanding of how Auger emitters induce cell death at a cellular and molecular level, supporting the targeted radiomedical applications of Auger emitters.

Boron neutron capture in prostate cancer cells.

A modified enhanced thermal neutron beam (METNB) assembly at Fermilab was used to irradiate borylphenylalanine (BPA) treated human prostate cancer cells, DU 145. Acceptable cellular uptake levels of BPA and no BPA cytotoxicity were observed. In the absence of BPA, the relative biological effectiveness (RBE) of the METNB was determined to be 2.

Gadolinium neutron capture in glioblastoma multiforme cells.

Purpose: A proof of principle for cell killing by Gadolinium (Gd) neutron capture in Magnevist preloaded Glioblastoma multiforme (GBM) cells is provided.

Materials And Methods: U87cells were pre-loaded with 5 mg/ml Magnevist (Gd containing compound) and irradiated using an enhanced neutron beam developed at NIU Institute for Neutron Therapy at Fermilab. These experiments were possible because of an enhanced fast neutron therapy assembly designed to use the fast neutron beam at Fermilab to deliver a neutron beam containing a greater fraction of thermal neutrons and because of the development of improved calculations for dose for the enhanced neutron beam.

Non-DNA-binding platinum anticancer agents: Cytotoxic activities of platinum-phosphato complexes towards human ovarian cancer cells.

DNA is believed to be the molecular target for the cytotoxic activities of platinum (Pt) anticancer drugs. We report here a class of platinum(II)- and platinum(IV)-pyrophosphato complexes that exhibit cytotoxicity comparable with and, in some cases, better than cisplatin in ovarian cell lines (A2780, A2780/C30, and CHO), yet they do not show any evidence of covalent binding to DNA. Moreover, some of these compounds are quite effective in cisplatin- and carboplatin-resistant cell line A2780/C30.

Using Hoechst 33342 to target radioactivity to the cell nucleus.

We have explored the use of Hoechst 33342 (H33342) to carry radioactivity to the cell nucleus. H33342 enters cells and targets DNA at adenine-thymine-rich regions of the minor groove. Considerable membrane blebbing and ruffling occur in CHO cells within minutes after its addition to the culture medium in micromolar quantities.

GammaH2AX foci induced by gamma rays and 125idU decay.

Purpose: GammaH2AX foci formation was investigated after gamma irradiation and after accumulating 125IdU decays to study the DNA double strand break (dsb) damage repair response in human breast cancer cells, MCF-7.

Materials And Methods: Confocal laser scanning microscopy (CLSM) was used to detect yH2AX foci formed in response to DNA dsbs induced by 0, 0.5, 1, 2 and 5 Gy gamma irradiation and 125IdU decays accumulated at -90 degrees C in human breast cancer cells, MCF-7.

Cytotoxicity of 125I-oestrogen decay in non-oestrogen receptor-expressing human breast cancer cells, MDA-231 and oestrogen receptor-expressing MCF-7 cells.

Purpose: To compare the cytotoxicity of 125I-oestrogen (E-17alpha[125I]iodovinyl-11betamethoxyoestradiol or 125IVME2) decay accumulation in human breast adenocarcinoma cells that do not express oestrogen receptor (ER) (MDA-231 cells) with human breast adenocarcinoma cells that do express ER (MCF-7 cells).

Materials And Methods: MDA-231 cells were labelled with 125IVME2 or [125I]iododeoxyuridine (125IdU), frozen for decay accumulation, thawed and then plated for colony formation. gamma-irradiation survival was also determined.

Relative biological effectiveness of accumulated 125IdU and 125I-estrogen decays in estrogen receptor-expressing MCF-7 human breast cancer cells.

The therapeutic potential for delivering a cytotoxic dose of radiation (using the decay of Auger-electron emitters) to the cell nucleus of cancer cells that express estrogen receptors (ERs) by radiolabeled estrogen was investigated in the ER-expressing human breast cancer cell line, MCF-7. The radiolabeled estrogen/ER complex irradiates the cell nucleus by binding specific DNA sequences called estrogen response elements (EREs). Cell clonogenicity and induction of DNA double-strand breaks (DSBs) by gamma radiation or accumulation of (125)I-iododeoxyuridine ((125)IdU) or E-17alpha[(125)I]iodovinyl-11betamethoxyestradiol ((125)IVME2) decays were determined.

DNA damage induction by 125I-estrogen.

DNA damage induced by the radioactive decay of 125I-estrogen (125I-VME2) in an estrogen receptor expressing CHO cell line, CHO-ER, was measured. 125I-VME2 targeted 125I atoms proximal to DNA estrogen response elements (EREs). 125I decays were accumulated at -135 degrees C, and thereafter assayed by alkaline and neutral filter elution techniques to measure DNA single strand break (ssb) and double strand break (dsb) induction respectively.

Nuclear scaffold organization in the X-ray sensitive Chinese hamster mutant cell line, xrs-5.

Nuclear organization was probed in the radiation-sensitive Chinese hamster ovary CHO) cell line, xrs-5, and compared with parental CHO K1 cells using the resinless section technique and DNase I digestions. The resinless section data showed no gross morphological differences in core filaments from the nuclear scaffolds of unirradiated CHO K1 and xrs-5 cells. However, the nuclear scaffolds of irradiated xrs-5 cells (1 Gy) had significantly increased ground substance.

Morphological characterization of the radiation sensitive cell line, xrs-5.

Morphometric analysis was performed on the radiation sensitive Chinese hamster ovary (CHO) xrs-5 cell line, reverting xrs-5 cells and parental K1 cells. Several ultrastructural parameters (increased nuclear envelope membrane separation, cell and nuclear volume, nuclear to cytoplasmic ratio, and the nuclear surface area per unit volume of the cell) were measured and correlated with radiation sensitivity. A trend in increased cell size and radiosensitivity was observed.

Cytotoxicity of 125I decay in the DNA double strand break repair deficient mutant cell line, xrs-5.

The survival of parental Chinese hamster ovary (CHO) K1 cells and the DNA double strand break (DSB) repair deficient mutant, xrs-5 was determined after accumulation of 125I decays. Both CHO and xrs-5 cells were extremely sensitive to accumulated 125I decays. The D0 values for CHO and xrs-5 cells were 40 and approximately 7 decays per cell, respectively.

Faster rates of DNA unwinding under alkaline conditions in xrs-5 cells may reflect chromatin structure alterations.

The Chinese hamster ovary (CHO) cell line xrs-5 is a radiation-sensitive mutant isolated from CHO-K1 cells. The radiation sensitivity is associated with a defect in DNA double-strand break rejoining. The DNA alkaline unwinding technique was used to measure the DNA single-strand breakage caused by gamma-rays in xrs-5 and CHO-K1 cells.

Changes in the nuclear structure in the radiation-sensitive CHO mutant cell, xrs-5.

The structural organization of the cell nucleus was investigated by transmission electron microscopy in the radiosensitive Chinese hamster ovary (CHO) cell mutant, xrs-5 (D0 = 45 cGy), relative to parental K1 cells (D0 = 200 cGy). In 99% of all xrs-5 cells, the outer layer of the nuclear envelope was separated from the inner layer, while 96% of K1 cells had closely apposed layers. This separation of the inner and outer layers of the nuclear envelope in xrs-5 cells was not explained by an increased susceptibility of xrs-5 cells to osmotically induced changes because (1) xrs-5 cells retained the altered nuclear periphery even when several different fixation protocols were used and (2) xrs-5 cells were not more susceptible to cell lysis as measured by trypan blue dye exclusion or by the extracellular presence of lactate dehydrogenase.

Thermal sensitivity of CHO cells with different shapes.

Confirming previous reports, we observed that rounded Chinese hamster ovary (CHO) cells from suspension culture were more resistant to heat kill than flattened CHO cells from monolayer culture. Cell survival was quantitatively described by determining full cell survival curves for flattened versus rounded CHO cells after exposure to 43, 44, 45 and 46 degrees C and calculating the To values. The cell survival responses of the rounded cells were significantly different from those of the flattened cells.

Measurement of radiation-induced DNA damage using gel electrophoresis or neutral filter elution shows an increased frequency of DNA strand breaks after exposure to pH 9.6.

The filter elution technique using nondenaturing conditions is widely used to assay DNA double-strand break (DSB) induction and repair. It has been reported that in the measurement of strand breaks higher rates of elution and of initial rejoining are obtained at pH 9.6 compared to pH 7.