Reumatismo. 2012; 63(4): 263-75
Paparo F, Fabbro E, Ferrero G, Piccazzo R, Revelli M, Camellino D, Garlaschi G, Cimmino MA

Gout, calcium pyrophosphate dihydrate (CPPD) deposition disease, and calcium hydroxyapatite deposition disease (HADD) are the three most common crystal-induced arthropathies. Multimodality imaging may help in their diagnosis, and is useful for a precise and comprehensive assessment and grading of the related osteoarticular damage. Plain film radiography, due to its low cost and wide availability, is the first imaging technique to be used in crystal deposition diseases, providing well-known and specific findings for CPPD deposition disease and HADD, while it may undergrade the early osteoarticular lesions in gouty patients. Ultrasonography (US) is a radiation-free approach that accurately depicts crystal deposits in cartilage, peri- and intra-articular soft tissues, but it does not give a panoramic view of the affected joints. Cross-sectional imaging techniques can examine crystal deposits in the spine and axial joints. CT has the potential to distinguish monosodium urate (MSU) crystals from calcium containing crystals, due to their different attenuation values. MRI may demonstrate synovitis, erosions and bone marrow edema in gouty patients and it may differentiate tophi from other soft tissue nodules due to its high contrast resolution and power of tissue characterization.

Front Genet. 2011; 2: 84
Christensen BC, Marsit CJ

This review considers the emerging relationships between environmental factors and epigenetic alterations and the application of genome-wide assessments to better define these relationships. First we will briefly cover epigenetic programming in development, one-carbon metabolism, and exposures that may disrupt normal developmental programming of epigenetic states. In addition, because a large portion of epigenetic research has focused on cancer, we discuss exposures associated with carcinogenesis including asbestos, alcohol, radiation, arsenic, and air pollution. Research on other exposures that may affect epigenetic states such as endocrine disruptors is also described, and we also review the evidence for epigenetic alterations associated with aging that may reflect cumulative effects of exposures. From this evidence, we posit potential mechanisms by which exposures modify epigenetic states, noting that understanding the true effect of environmental exposures on the human epigenome will require additional research with appropriate epidemiologic studies and application of novel technologies. With a more comprehensive understanding of the affects of exposures on the epigenome, including consideration of genetic background, the prediction of the toxic potential of new compounds may be more readily achieved, and may lead to the development of more personalized disease prevention and treatment strategies.

J Biol Chem. 2012 Feb 1;
Yao Y, Harrison KA, Al-Hassani M, Murphy RC, Rezania S, Konger RL, Travers JB

To date, oxidized glycerol-phosphocholines (Ox-GPC) with Platelet-activating factor (PAF) activity produced non-enzymatically have not been definitively demonstrated to mediate any known disease processes. Here we provide evidence that these Ox-GPC play a pivotal role in the photosensitivity associated with the deficiency of the DNA repair protein Xeroderma Pigmentosum complementation group A (XPA). It should be noted that XPA-deficient cells are known to have decreased antioxidant defenses. These studies demonstrate that treatment of human XPA-deficient fibroblasts with the pro-oxidative stressor, ultraviolet B radiation (UVB), resulted in increased reactive oxygen species and PAF-receptor (PAF-R) agonistic activity in comparison to gene-corrected cells. The UVB-generated PAF-R agonists were inhibited by antioxidants. UVB irradiation of XPA-deficient (Xpa-/-) mice also resulted in increased PAF-R agonistic activity and skin inflammation in comparison to control mice. The increased UVB-mediated skin inflammation and TNF-α production in Xpa-/- mice were blocked by systemic antioxidants and by PAF-R antagonists. Structural characterization of PAF-R stimulating activity in UVB-irradiated XPA-deficient fibroblasts using mass spectrometry revealed increased levels of sn-2 short-chained Ox-GPC along with native PAF. These studies support a critical role for PAF-R agonistic Ox-GPC in the pathophysiology of XPA photosensitivity.

Head Neck. 2012 Feb 2;
Affolter A, Drigotas M, Fruth K, Schmidtmann I, Brochhausen C, Mann WJ, Brieger J

BACKGROUND: Irradiation-induced signaling via the 2 pathways, Raf-MEK-ERK and PI3K-Akt, is known to be closely associated with a limited response to radiotherapy. In the present study we analyzed the relevance of constitutively active K-Ras for postradiogenic pathway stimulation and the option of coordinated inhibition to overcome these rescue mechanisms. METHODS: We used 2 epithelial tumor cell lines as a model system, one of them harboring a G12S K-Ras mutation. Cells were irradiated and the effect of combined treatment with ionizing radiation and inhibitors on the expression of pERK and pAkt was determined by Western blotting. Additionally, clonogenic assays were performed to functionally analyze survival of the cell lines. RESULTS: Compared with the nonmutated cells we observed the G12S cell line showing a clearly reduced response to inhibitor treatment under irradiation. In the case of pharmacologic inhibition of 1 of the pathways a compensatory upregulation of the second cascade leading to increased clonogenic survival seems feasible. However, there was a good functional response of this cell line to double inhibition with both compounds represented by minimized colony forming ability. The activation of ERK and Akt after irradiation was confirmed in xenotransplants showing elevated postradiogenic protein levels. CONCLUSION: With our data we confirmed our hypothesis of postradiogenic constitutive activation of the 2 pathways both required for Ras-mediated radioresistance in epithelial cells. If this effect should prove itself as a general mechanism in Ras-mutated tumors, application of specific inhibitors to block both cascades in parallel could contribute to enhance radiosensitivity in these types of cancer. © 2012 Wiley Periodicals, Inc. Head Neck, 2012.

Head Neck. 2012 Feb 2;
Galloway TJ, Lango MN, Burtness B, Mehra R, Ruth K, Ridge JA

BACKGROUND: The purpose of this study was to determine whether the incidence of bilateral neck disease tonsillar cancer is rising. METHODS: We reviewed tonsillar cancer incidence data from the Surveillance, Epidemiology, and End Results (SEER) Program of the National Cancer Institute. RESULTS: The annual incidence of advanced neck disease (≥N2) with small primary tonsillar cancer is increasing (annual percent change [APC]; p < .05) during 2 evaluable time frames (1988-2003 and 2004-2008). The increase for small primary tonsillar cancer from 2004 to 2008 is associated with increased ipsilateral disease (ie, T1-2N2a-b, APC 10.6%; p < .05) rather than bilateral neck disease (T1-2N2c, APC 5.9%, APC = NS). The increase in bilateral neck disease is less than the overall rise in T1 to 2 tonsillar cancer (APC 7.2%; p < .05). CONCLUSION: In the human papillomavirus (HPV) era, bilateral neck disease is increasingly common. This seems to be a consequence of the increasing incidence of tonsillar cancer rather than a new biologic behavior. © 2012 Wiley Periodicals, Inc. Head Neck, 2012.

Curr Oncol Rep. 2012 Feb 3;
Thompson PA, Chintagumpala M

Pediatric soft-tissue and bone sarcomas are a heterogeneous group of tumors of mesenchymal origin which affect approximately 1,500 children in the United States each year. Using multimodal therapy (surgery, radiation, and chemotherapy), the overall 5-year survival rate for children with soft-tissue and bone sarcomas is approximately 60%-70%. However, the prognosis for children with metastatic or recurrent disease is poor; and, furthermore, the improvements in the overall cure rate have slowed. It is highly unlikely that further advances in the treatment of pediatric soft-tissue and bone sarcomas will come from traditional cytotoxic chemotherapy. Based on research advances in understanding the biology of pediatric soft-tissue and bone sarcomas, improved cure rates will likely be driven by new types of treatment which target the specific abnormalities within these tumors. These new targeted therapies may include small molecules, antibodies, or other immunotherapies. This review briefly describes the biology of the major types of pediatric sarcomas, discusses potential targets for new therapy, and highlights some recent and current clinical trials using targeted therapy.

Tumour Biol. 2012 Feb 3;
Gedda L, Edwards K

The Nuclisome concept builds on a novel two-step targeting strategy with the aim to deliver short-range Auger-electron-emitting radionuclides to nuclear DNA of tumor cells. The concept is based on the use of Nuclisome-particles, i.e., tumor-targeted PEG-stabilized liposomes loaded with a unique DNA-intercalating compound that enables specific and effective delivery of radionuclides to DNA. The specific and potent two-step targeting leads to eradication of tumor cells while toxicity to normal organs is reduced to a minimum. Results of in vitro and in vivo studies point towards the Nuclisome concept as a promising strategy for the treatment of small tumor masses and, in particular, for the elimination of spread single cells and micrometastases.

Tumour Biol. 2012 Feb 3;
Kang KA, Maeng YH, Zhang R, Yang YR, Piao MJ, Kim KC, Kim GY, Kim YR, Koh YS, Kang HK, Hyun CL, Chang WY, Hyun JW

Heme oxygenase-1 (HO-1) catabolizes heme into carbon monoxide, biliverdin, and free iron which mediate its protective effect against oxidative stress. The aim of the present study was to determine the expression level and activity of HO-1 in Korean colon cancer tissues and cell lines. HO-1 protein expression was higher (>1.5-fold) in tumor tissues than in adjacent normal tissues in 14 of 20 colon cancer patients, and HO-1 protein expression was closely correlated with HO-1 enzyme activity in cancer tissues. Immunohistochemical data confirmed that HO-1 protein was expressed at a higher level in colon cancer tissues than in normal mucosa. Furthermore, HO-1 mRNA and protein expression and enzyme activity were higher in the colon cancer cell lines Caco-2, SNU-407, SNU-1033, HT-29, and SW-403 than in the normal fetal human colon cell line FHC. Treatment with the HO-1 inhibitor zinc protoporphyrin decreased the viability of colon cancer cell lines. These data indicate that HO-1 may serve as a clinically useful biomarker of colon cancer and as a target for anticolon cancer drugs.

Australas Phys Eng Sci Med. 2012 Feb 3;
Oliver CP, Butler DJ, Webb DV

The Australian radiation protection and nuclear safety agency (ARPANSA) has continuously provided a level 1 mailed thermoluminescence dosimetry audit service for megavoltage photons since 2007. The purpose of the audit is to provide an independent verification of the reference dose output of a radiotherapy linear accelerator in a clinical environment. Photon beam quality measurements can also be made as part of the audit in addition to the output measurements. The results of all audits performed between 2007 and 2010 are presented. The average of all reference beam output measurements calculated as a clinically stated dose divided by an ARPANSA measured dose is 0.9993. The results of all beam quality measurements calculated as a clinically stated quality divided by an ARPANSA measured quality is 1.0087. Since 2011 the provision of all auditing services has been transferred from the Ionizing Radiation Standards section to the Australian Clinical Dosimetry Service (ACDS) which is currently housed within ARPANSA.

Australas Phys Eng Sci Med. 2012 Feb 1;
Moorrees J, Bezak E

Organ motion is a substantial concern in the treatment of thoracic tumours using radiotherapy. A number of technologies have evolved in order to address this both during computed tomography (CT) imaging and radiation delivery. This review paper investigates the various technologies which have been developed in the field of CT scanning as well as their accuracy, cost and the implications of their clinical implementation. The scanning modalities covered include: slow CT, breath hold CT, gated CT and retrospectively correlated CT (4DCT). It was found that there are advantages and drawbacks to each of the mentioned techniques relating to patient dose, scan time, extra equipment and workload. Also some scanning techniques are only compatible with certain treatment modalities which would further influence the decision as to which technologies to implement.

Pediatr Radiol. 2012 Feb 3;
Newman B, Callahan MJ

Pediatr Radiol. 2012 Feb 3;
Cohen MD