Effects of Obesity on the Regulation of Macrophage Population in the Prostate Tumor Microenvironment.

Obesity is associated with a greater risk of prostate cancer mortality. However, the mechanisms connecting obesity to the progression of prostate cancer remain unknown. This study determined the impact of obesity on macrophage recruitment and tumor-associated macrophage (TAM) polarization in the prostate tumor microenvironment, since a high concentration of TAMs in tumors has been linked to progression in prostate cancer. We utilized an in vitro model in which pre-adipocytes, prostate cancer cells, and macrophages were exposed to sera from obese or nonobese men, or conditioned media generated under obese or nonobese conditions. Matrigel invasion chambers were used to assess macrophage recruitment in vitro, and immunohistochemical analysis evaluated recruitment in a PTEN knockout mouse model. qPCR was used to measure mRNA levels of CCL2, COX-2, IL-10, TGF-beta, VEGF-A, arginase-1, and MMP-9. PGE2 production was measured by ELISA. Obesity increased macrophage and TAM recruitment, and increased mRNA levels of TAM markers in macrophages. Similarly, obese conditions increased CCL2 and COX-2 expression, as well as PGE2 levels in prostate cancer cells. COX-2 inhibition resulted in lower expression of obesity-induced TAM markers. Our data suggest that obesity promotes macrophage infiltration into the prostate tumor microenvironment, and induces TAM polarization through the COX-2/PGE2 pathway.

A diagnosis of prostate cancer and pursuit of active surveillance is not followed by weight loss: potential for a teachable moment.

BACKGROUND: Obesity is a risk factor for incident prostate cancer (PC) as well as risk of disease progression and mortality. We hypothesized that men diagnosed with lower-risk PC and who elected active surveillance (AS) for their cancer management would likely initiate lifestyle changes that lead to weight loss. METHODS: Patients were enrolled in the Prostate Active Surveillance Study (PASS), a multicenter prospective biomarker discovery and validation study of men who have chosen AS for their PC. Data from 442 men diagnosed with PC within 1 year of study entry who completed a standard of care 12-month follow-up visit were analyzed. We examined the change in weight and body mass index (BMI) over the first year of study participation. RESULTS: After 1 year on AS, 7.5% (33/442) of patients had lost 5% or more of their on-study weight. The proportion of men who lost 5% or more weight was similar across categories of baseline BMI: normal/underweight (8%), overweight (6%) and obese (10%, χ2 test P=0.44). The results were similar for patients enrolled in the study 1 year or 6 months after diagnosis. By contrast, after 1 year, 7.7% (34/442) of patients had gained >5% of their weight. CONCLUSIONS: Only 7.5% of men with low-risk PC enrolled in AS lost a modest (⩾5%) amount of weight after diagnosis. Given that obesity is related to PC progression and mortality, targeted lifestyle interventions may be effective at this 'teachable moment', as men begin AS for low-risk PC.

In vivo prostate cancer detection and grading using restriction spectrum imaging-MRI.

BACKGROUND: Magnetic resonance imaging (MRI) is emerging as a robust, noninvasive method for detecting and characterizing prostate cancer (PCa), but limitations remain in its ability to distinguish cancerous from non-cancerous tissue. We evaluated the performance of a novel MRI technique, restriction spectrum imaging (RSI-MRI), to quantitatively detect and grade PCa compared with current standard-of-care MRI. METHODS: In a retrospective evaluation of 33 patients with biopsy-proven PCa who underwent RSI-MRI and standard MRI before radical prostatectomy, receiver-operating characteristic (ROC) curves were performed for RSI-MRI and each quantitative MRI term, with area under the ROC curve (AUC) used to compare each term's ability to differentiate between PCa and normal prostate. Spearman rank-order correlations were performed to assess each term's ability to predict PCa grade in the radical prostatectomy specimens. RESULTS: RSI-MRI demonstrated superior differentiation of PCa from normal tissue, with AUC of 0.94 and 0.85 for RSI-MRI and conventional diffusion MRI, respectively (P=0.04). RSI-MRI also demonstrated superior performance in predicting PCa aggressiveness, with Spearman rank-order correlation coefficients of 0.53 (P=0.002) and -0.42 (P=0.01) for RSI-MRI and conventional diffusion MRI, respectively, with tumor grade. CONCLUSIONS: RSI-MRI significantly improves upon current noninvasive PCa imaging and may potentially enhance its diagnosis and characterization.

Novel technique for characterizing prostate cancer utilizing MRI restriction spectrum imaging: proof of principle and initial clinical experience with extraprostatic extension.

BACKGROUND: Standard magnetic resonance imaging (MRI) of the prostate lacks sensitivity in the diagnosis and staging of prostate cancer (PCa). To improve the operating characteristics of prostate MRI in the detection and characterization of PCa, we developed a novel, enhanced MRI diffusion technique using restriction spectrum imaging (RSI-MRI). METHODS: We compared the efficacy of our novel RSI-MRI technique with standard MRI for detecting extraprostatic extension (EPE) among 28 PCa patients who underwent MRI and RSI-MRI prior to radical prostatectomy, 10 with histologically proven pT3 disease. RSI cellularity maps isolating the restricted isotropic water fraction were reconstructed based on all b-values and then standardized across the sample with z-score maps. Distortion correction of the RSI maps was performed using the alternating phase-encode technique. RESULTS: 27 patients were evaluated, excluding one patient where distortion could not be performed. Preoperative standard MRI correctly identified extraprostatic the extension in two of the nine pT3 (22%) patients, whereas RSI-MRI identified EPE in eight of nine (89%) patients. RSI-MRI correctly identified pT2 disease in the remaining 18 patients. CONCLUSIONS: In this proof of principle study, we conclude that our novel RSI-MRI technology is feasible and shows promise for substantially improving PCa imaging. Further translational studies of prostate RSI-MRI in the diagnosis and staging of PCa are indicated.

Development of radiographic chest phantoms.

Diagnostic imaging studies, particularly in chest radiography, require adequate phantoms. Two such phantoms have been made and used; one is a semianthropomorphic phantom and the other is a geometric phantom with embedded test objects. These phantoms, constructed of epoxy resin-based solid water, are described in detail and compared to a common commercial phantom.

Radiation therapy and clinical physics practices in the midwest (1982-1986).

As a part of an on-site physics review procedure, the Midwest Center for Radiological Physics (MWCRP) interviewed midwest clinical radiotherapy physicists and radiation therapists in institutions that participated in federally funded Cancer Control Programs. Information from 77 institutions was compiled regarding types of megavoltage units, daily patient load, radiotherapy personnel, treatment planning responsibilities, dosimetric practices, and treatment planning computers. Even though some practices, such as frequency of patient charge checks, were consistent throughout the midwest, other practices varied considerably such as patient load with the number of megavoltage units. This information may be useful either for planning a new facility, considering the needs for staff, or for comparing existing practices and responsibilities.

Calibration and use of the Wisconsin kVp test cassette.

The Ardran-Crooks kVp test cassette is widely used in diagnostic radiology to provide a rapid, simple, noninvasive measurement of x-ray tube potential. A modified version of this cassette called the Wisconsin kVp Test Cassette was introduced commercially in the U. S. in 1972. Since then, the method of calibration of these cassettes has changed significantly. Wisconsin kVp Test Cassettes calibrated by the manufacturer prior to August 1982 may yield underestimates of kVp measurements, particularly when using the 90-110 and 110-130 kVp regions with single-phase units. In August 1982 significant improvements in the calibration methods were implemented. The resultant change in calibration is demonstrated by data from the Centers for Radiological Physics. Present calibration methods are believed to be accurate within the greater of +/- 2 kVp or 2% of actual peak tube potential. Proper use of the cassette is necessary to achieve this level of accuracy.

Predictors and correlates of adaptive functioning in children with developmental disorders.

Autism is a developmental disorder marked by impairments in socialization, communication, and perseverative behavior and is associated with cognitive impairment and deficits in adaptive functioning. Research has consistently demonstrated that children with autism have deficits in adaptive functioning more severe than their cognitive deficits. This study investigates the correlates and predictors of adaptive functioning as measured by the Vineland Adaptive Behavior Scales in high- and low-functioning children with autism and their age and nonverbal IQ matched controls. Thirty-five 9-year-old children with high-functioning autism (HAD) were compared with 31 age-matched children with developmental language disorder (DLD), and 40 9-year-old children with low-functioning autism (LAD) were compared with 17 age-matched children with low IQ on adaptive functioning, IQ, autistic symptomology, and tests of language and verbal memory. Results indicate that both groups with autism were significantly impaired compared to their matched controls on Socialization and Daily Living, but not Communication and that these impairments were more pronounced in the HAD group than in the LAD group. Adaptive behavior was strongly correlated with autistic symptomology only in the HAD group. Regression analyses indicated that IQ was strongly predictive of adaptive behavior in both low-functioning groups, but tests of language and verbal memory predicted adaptive behavior in the higher functioning groups. Results suggest that IQ may act as a limiting factor for lower functioning children but higher functioning children are impaired by specific deficits, including autistic symptomology and impaired language and verbal memory.

Assessment of genetic variability and relatedness among atypical Aeromonas salmonicida from marine fishes, using AFLP-fingerprinting.

Atypical strains of Aeromonas salmonicida are the causal agent of atypical furunculosis or ulcer disease in various fish species, including spotted wolffish Anarhichas minor, which is a promising species in the Norwegian fish-farming industry. Isolates of atypical A. salmonicida comprise a very heterogenous group showing large variety in biochemical, molecular and virulence characteristics. The genetic variability among atypical isolates from wolffish was characterised using amplified fragment length polymorphism analysis: AFLP-fingerprinting. Additional isolates from halibut Hippoglossus hippoglossus, turbot Scophthalmus maximus, cod Gadus morhua and several salmonid fishes were included for assessment of variability and relatedness among a total of 56 atypical isolates of A. salmonicida. They were compared to reference strains of A. salmonicida subspecies and to other Aeromonas species pathogenic in fishes. AFLP-fingerprints subjected to similarity analysis yielded a grouping of the isolates into several clusters, revealing genetic heterogeneity among the isolates. There seems to be a correlation between genetic similarity among isolates and the fish host. The Icelandic isolates, mainly from cod, formed a very homogeneous subcluster, which was closely related to the wolffish isolates. All atypical isolates from spotted and common wolffish grouped together in a large cluster and appear to be very homogeneous, even though they had been isolated over a period of 8 yr at different locations in Norway. On the other hand, most of the isolates from turbot and halibut grouped together into 2 different clusters, while the 9 atypical isolates from salmonids appeared in 4 different clusters. Thus, the atypical isolates of A. salmonicida from halibut, turbot and salmonid fishes seem to be more genetically diverse than those from wolffish and cod.

The use of Teflon-embedded calcium sulphate: dysprosium thermoluminescent dosimeters for chest radiography.

As part of a U.S. multi-regional pilot study conducted by the six Centers for Radiological Physics, 12-mm-diameter by 0.4-mm-thick CaSO4:Dy Teflon-embedded discs were evaluated and used to measure patient entrance exposure on 60 "average" patients at 12 clinical centers. The discs were found to have adequate sensitivity, reproducibility and linearity up to 69.7 microC kg-1 (270 mR). The minimum measurable exposure was estimated as 0.4 microC kg-1 (1.5 mR). All responses were corrected for energy dependence, which varied +/- 20% from 1.7 to 6.5 mm Al half-value layer. Patient entrance exposure values ranged from 1.3 to 28 microC kg-1 (5 to 110 mR), with a median value of 5.2 microC kg-1 (20 mR). This value agreed with exposure measurements made on the chest radiography equipment using an ionization chamber and a phantom which simulated an "average" patient, and with published Nationwide Evaluation of X-Ray Trends (NEXT) data for the same period.

Traumatic brain injury and marital relationships: a literature review.

This is a review of the research regarding the effects of traumatic brain injury (TBI) on the marital relationship. Individuals who have withstood a severe traumatic brain injury usually exhibit a range of cognitive and behavioural disabilities. Typical problems outlined in the research include: attention and concentration deficits, memory and information-processing deficits, judgement and perception difficulties. While these impediments pose problems for community re-integration, they may become sources of difficulty for the spouse. The following report critically examines the literature on the effects of head injury on marital relationships. This research has demonstrated that spouses' reactions to TBI include feelings of anxiety, isolation, and loss. In addition, this literature review shows that there is a dearth of research that has regarded the individual with TBI to be a valid source of information, or has considered women with TBI in a marital situation.

Antibody binding to the beta-subunit of deglycosylated chorionic gonadotropin converts the antagonist to an agonist.

The murine Leydig tumor cell line, MLTC-1, has a gonadotropin-responsive adenylate cyclase system. Binding of human chorionic gonadotropin (hCG) stimulates the accumulation of cyclic AMP in these cells. Chemically deglycosylated hCG (DG-hCG) is an antagonist that binds with high affinity to the gonadotropin receptor, but fails to stimulate adenylate cyclase. This antagonism can be reversed if the binding of DG-hCG is followed by treatment of the DG-hCG-receptor complex with antibodies against hCG. Polyclonal antibodies against DG-hCG were raised in rabbits. These antibodies were strongly cross-reactive with hCG, bound to both the alpha- and beta-subunits of hCG and DG-hCG, and reversed the antagonism of DG-hCG. The antiserum was divided into two fractions by affinity chromatography on hCG-Sepharose. The fraction that was not retained reacted only with DG-hCG (DG-hCG antibodies) and, on Western blots, bound to both the alpha- and beta-subunits of DG-hCG. DG-hCG antibodies did not reverse the antagonism of DG-hCG. However, using 125I-protein A, we were able to detect binding of these antibodies to the cell surface DG-hCG-receptor complex. The fraction of antibodies retained by the affinity column reacted with both DG-hCG and hCG (DG-hCG/hCG antibodies). On Western blots, DG-hCG/hCG antibodies bound to the beta-subunit, but only weakly to the alpha-subunit of both hCG and DG-hCG. These antibodies also bound to the cell surface DG-hCG-receptor complex. In addition, DG-hCG/hCG antibodies were able reverse the antagonism of DG-hCG. Reversal of DG-hCG antagonism by the whole antiserum was blocked by the beta- but not the alpha-subunit of hCG. Polyclonal antiserum against the beta- but not the alpha-subunit of hCG reversed the antagonism of DG-hCG. From these results, we conclude that antibody binding to specific determinants common to both native and deglycosylated beta-subunit reverses the antagonism of DG-hCG. In addition, antibodies directed against unique determinants on the deglycosylated beta-subunit are not capable of reversing the antagonism of DG-hCG.