Weight gain and obesity rates in transgender and gender-diverse adults before and during hormone therapy.

BACKGROUND: Obesity rates and weight changes in adults on gender-affirming hormone therapy are lacking or limited by small sample sizes, duration, and location. SUBJECTS/METHODS: This longitudinal study followed the body mass index and body weights of 470 transgender and gender-diverse adult patients (247 transfeminine and 223 transmasculine; mean age, 27.8 years) seen at a Federally Qualified Health Center and an academic endocrinology practice, both in Washington DC USA. Body weight and body mass index were recorded at baseline and at multiple follow-up clinical visits up to 57 months after the initiation of gender-affirming hormone therapy. The outcomes of this study were the changes to body weight and obesity rates following hormone therapy. RESULTS: Within 2-4 months of starting gender-affirming hormone therapy, the mean body weight increased in the transmasculine group by 2.35 (1.15-3.55) kg and further increased beyond 34 months. Among the transfeminine group, the mean body weight was stable for the first 21 months of hormone therapy and then began to steadily increase, particularly in those under 30 years old. The prevalence of obesity at baseline was 25% in the transfeminine group and 39% in the transmasculine group. Following the initiation of hormone therapy, rates of obesity ranged from 42 to 52% among the transmasculine group and 21 to 30% among transfeminine group. Following 11-21 months of hormone therapy, weight gain ≥5 kg was seen among 21% of transfeminine individuals and 30% of transmasculine individuals. CONCLUSIONS: As compared with transfeminine individuals, transmasculine individuals have greater rates of obesity and weight gain before and during hormone therapy. Body weight and body mass index should be routinely monitored before and after the initiation of gender-affirming hormone therapy. Multidisciplinary weight-reduction interventions should be promoted where appropriate.

RESISTing the Need to Quantify: Putting Qualitative FDG-PET/CT Tumor Response Assessment Criteria into Daily Practice.

Tumor response assessments are essential to evaluate cancer treatment efficacy and prognosticate survival in patients with cancer. Response criteria have evolved over multiple decades, including many imaging modalities and measurement schema. Advances in FDG-PET/CT have led to tumor response criteria that harness the power of metabolic imaging. Qualitative PET/CT assessment schema are easy to apply clinically, are reproducible, and yield good prognostic results. We present 3 such criteria, namely, the Lugano classification for lymphoma, the Hopkins criteria, and the Neck Imaging Reporting and Data Systems criteria for head and neck cancers. When comparing baseline PET/CTs with interim or end-of-treatment PET/CTs, radiologists can classify the tumor response as complete metabolic response, partial metabolic response, no metabolic response, or progressive disease, which has important implications in directing further cancer management and long-term patient prognosis. The purpose of this article is to review the progression of tumor response assessments from CT- and PET/CT-based quantitative and semi-quantitative systems to PET/CT-based qualitative systems; introduce the classification schema for these systems; and describe how to use these rapid, powerful, and qualitative PET/CT-based systems in daily practice through illustrative cases.

Anti-EGFR-resistant clones decay exponentially after progression: implications for anti-EGFR re-challenge.

BACKGROUND: Colorectal cancer (CRC) has been shown to acquire RAS and EGFR ectodomain mutations as mechanisms of resistance to epidermal growth factor receptor (EGFR) inhibition (anti-EGFR). After anti-EGFR withdrawal, RAS and EGFR mutant clones lack a growth advantage relative to other clones and decay; however, the kinetics of decay remain unclear. We sought to determine the kinetics of acquired RAS/EGFR mutations after discontinuation of anti-EGFR therapy. PATIENTS AND METHODS: We present the post-progression circulating tumor DNA (ctDNA) profiles of 135 patients with RAS/BRAF wild-type metastatic CRC treated with anti-EGFR who acquired RAS and/or EGFR mutations during therapy. Our validation cohort consisted of an external dataset of 73 patients with a ctDNA profile suggestive of prior anti-EGFR exposure and serial sampling. A separate retrospective cohort of 80 patients was used to evaluate overall response rate and progression free survival during re-challenge therapies. RESULTS: Our analysis showed that RAS and EGFR relative mutant allele frequency decays exponentially (r2=0.93 for RAS; r2=0.94 for EGFR) with a cumulative half-life of 4.4 months. We validated our findings using an external dataset of 73 patients with a ctDNA profile suggestive of prior anti-EGFR exposure and serial sampling, confirming exponential decay with an estimated half-life of 4.3 months. A separate retrospective cohort of 80 patients showed that patients had a higher overall response rate during re-challenge therapies after increasing time intervals, as predicted by our model. CONCLUSION: These results provide scientific support for anti-EGFR re-challenge and guide the optimal timing of re-challenge initiation.

Impact of genomic alterations on lapatinib treatment outcome and cell-free genomic landscape during HER2 therapy in HER2+ gastric cancer patients.

Background: To identify predictive markers for responders in lapatinib-treated patients and to demonstrate molecular changes during lapatinib treatment via cell-free genomics. Patients and methods: We prospectively evaluated the efficacy of combining lapatinib with capecitabine and oxaliplatin as first line neoadjuvant therapy in patients with previously untreated, HER2-overexpressing advanced gastric cancer. A parallel biomarker study was conducted by simultaneously performing immunohistochemistry and next-generation sequencing (NGS) with tumor and blood samples. Results: Complete response was confirmed in 7/32 patients (21.8%), 2 of whom received radical surgery with pathologic-confirmed complete response. Fifteen partial responses (46.8%) were observed, resulting in a 68.6% overall response rate. NGS of the 16 tumor specimens demonstrated that the most common co-occurring copy number alteration was CCNE1 amplification, which was present in 40% of HER2+ tumors. The relationship between CCNE1 amplification and lack of response to HER2-targeted therapy trended toward statistical significance (66.7% of non-responders versus 22.2% of responders harbored CCNE1 amplification; P = 0.08). Patients with high level ERBB2 amplification by NGS were more likely to respond to therapy, compared with patients with low level ERBB2 amplification (P = 0.02). Analysis of cfDNA showed that detectable ERBB2 copy number amplification in plasma was predictive to the response (100%, response rate) and changes in plasma-detected genomic alterations were associated with lapatinib sensitivity and/or resistance. The follow-up cfDNA genomics at disease progression demonstrated that there are emergences of other genomic aberrations such as MYC, EGFR, FGFR2 and MET amplifications. Conclusions: The present study showed that HER2+ GC patients respond differently according to concomitant genomic aberrations beyond ERBB2, high ERBB2 amplification by NGS or cfDNA can be a positive predictor for patient selection, and tumor genomic alterations change significantly during targeted agent therapy.

Abaloparatide-SC improves trabecular microarchitecture as assessed by trabecular bone score (TBS): a 24-week randomized clinical trial.

In a phase 2 trial of 222 postmenopausal women with osteoporosis aged 55 to 85 years randomized to one of three different doses of abaloparatide-SC, subcutaneous teriparatide, or placebo for 24 weeks, abaloparatide-SC resulted in improvements in skeletal microarchitecture as measured by the trabecular bone score. INTRODUCTION: Subcutaneous abaloparatide (abaloparatide-SC) increases total hip and lumbar spine bone mineral density and reduces vertebral and non-vertebral fractures. In this study, we analyzed the extent to which abaloparatide-SC improves skeletal microarchitecture, assessed indirectly by trabecular bone score (TBS). METHODS: This is a post hoc analysis of a phase 2 trial of 222 postmenopausal women with osteoporosis aged 55 to 85 years randomized to abaloparatide-SC (20, 40, or 80 µg), subcutaneous teriparatide (20 µg), or placebo for 24 weeks. TBS was measured from lumbar spine dual X-ray absorptiometry (DXA) images in 138 women for whom the DXA device was TBS software compatible. Assessments were made at baseline, 12 and 24 weeks. Between-group differences were assessed by generalized estimating equations adjusted for relevant baseline characteristics, and a pre-determined least significant change analysis was performed. RESULTS: After 24 weeks, TBS increased significantly by 2.27, 3.14, and 4.21% versus baseline in participants on 20, 40, and 80 µg abaloparatide-SC daily, respectively, and by 2.21% in those on teriparatide (p < 0.05 for each). The TBS in the placebo group declined by 1.08%. The TBS increase in each treatment group was significantly higher than placebo at 24 weeks (p < 0.0001 for each) after adjustment for age, BMI, and baseline TBS. A dose-response was observed at 24 weeks across the three doses of abaloparatide-SC and placebo (p = 0.02). The increase in TBS in the abaloparatide-SC 80 µg group was significantly greater than TPTD (p < 0.03). CONCLUSIONS: These results are consistent with an effect of abaloparatide-SC to improve lumbar spine skeletal microarchitecture, as assessed by TBS.

L-arginine promotes gut hormone release and reduces food intake in rodents.

AIMS: To investigate the anorectic effect of L-arginine (L-Arg) in rodents. METHODS: We investigated the effects of L-Arg on food intake, and the role of the anorectic gut hormones glucagon-like peptide-1 (GLP-1) and peptide YY (PYY), the G-protein-coupled receptor family C group 6 member A (GPRC6A) and the vagus nerve in mediating these effects in rodents. RESULTS: Oral gavage of L-Arg reduced food intake in rodents, and chronically reduced cumulative food intake in diet-induced obese mice. Lack of the GPRC6A in mice and subdiaphragmatic vagal deafferentation in rats did not influence these anorectic effects. L-Arg stimulated GLP-1 and PYY release in vitro and in vivo. Pharmacological blockade of GLP-1 and PYY receptors did not influence the anorectic effect of L-Arg. L-Arg-mediated PYY release modulated net ion transport across the gut mucosa. Intracerebroventricular (i.c.v.) and intraperitoneal (i.p.) administration of L-Arg suppressed food intake in rats. CONCLUSIONS: L-Arg reduced food intake and stimulated gut hormone release in rodents. The anorectic effect of L-Arg is unlikely to be mediated by GLP-1 and PYY, does not require GPRC6A signalling and is not mediated via the vagus. I.c.v. and i.p. administration of L-Arg suppressed food intake in rats, suggesting that L-Arg may act on the brain to influence food intake. Further work is required to determine the mechanisms by which L-Arg suppresses food intake and its utility in the treatment of obesity.

L-cysteine suppresses ghrelin and reduces appetite in rodents and humans.

BACKGROUND: High-protein diets promote weight loss and subsequent weight maintenance, but are difficult to adhere to. The mechanisms by which protein exerts these effects remain unclear. However, the amino acids produced by protein digestion may have a role in driving protein-induced satiety. METHODS: We tested the effects of a range of amino acids on food intake in rodents and identified l-cysteine as the most anorexigenic. Using rodents we further studied the effect of l-cysteine on food intake, behaviour and energy expenditure. We proceeded to investigate its effect on neuronal activation in the hypothalamus and brainstem before investigating its effect on gastric emptying and gut hormone release. The effect of l-cysteine on appetite scores and gut hormone release was then investigated in humans. RESULTS: l-Cysteine dose-dependently decreased food intake in both rats and mice following oral gavage and intraperitoneal administration. This effect did not appear to be secondary to behavioural or aversive side effects. l-Cysteine increased neuronal activation in the area postrema and delayed gastric emptying. It suppressed plasma acyl ghrelin levels and did not reduce food intake in transgenic ghrelin-overexpressing mice. Repeated l-cysteine administration decreased food intake in rats and obese mice. l-Cysteine reduced hunger and plasma acyl ghrelin levels in humans. CONCLUSIONS: Further work is required to determine the chronic effect of l-cysteine in rodents and humans on appetite and body weight, and whether l-cysteine contributes towards protein-induced satiety.

Preclinical screening of histone deacetylase inhibitors combined with ABT-737, rhTRAIL/MD5-1 or 5-azacytidine using syngeneic Vk*MYC multiple myeloma.

Multiple myeloma (MM) is an incurable malignancy with an unmet need for innovative treatment options. Histone deacetylase inhibitors (HDACi) are a new class of anticancer agent that have demonstrated activity in hematological malignancies. Here, we investigated the efficacy and safety of HDACi (vorinostat, panobinostat, romidepsin) and novel combination therapies using in vitro human MM cell lines and in vivo preclinical screening utilizing syngeneic transplanted Vk*MYC MM. HDACi were combined with ABT-737, which targets the intrinsic apoptosis pathway, recombinant human tumour necrosis factor-related apoptosis-inducing ligand (rhTRAIL/MD5-1), that activates the extrinsic apoptosis pathway or the DNA methyl transferase inhibitor 5-azacytidine. We demonstrate that in vitro cell line-based studies provide some insight into drug activity and combination therapies that synergistically kill MM cells; however, they do not always predict in vivo preclinical efficacy or toxicity. Importantly, utilizing transplanted Vk*MYC MM, we report that panobinostat and 5-azacytidine synergize to prolong the survival of tumor-bearing mice. In contrast, combined HDACi/rhTRAIL-based strategies, while efficacious, demonstrated on-target dose-limiting toxicities that precluded prolonged treatment. Taken together, our studies provide evidence that the transplanted Vk*MYC model of MM is a useful screening tool for anti-MM drugs and should aid in the prioritization of novel drug testing in the clinic.

Retina restored and brain abnormalities ameliorated by single-copy knock-in of human NR2E1 in null mice.

Nr2e1 encodes a stem cell fate determinant of the mouse forebrain and retina. Abnormal regulation of this gene results in retinal, brain, and behavioral abnormalities in mice. However, little is known about the functionality of human NR2E1. We investigated this functionality using a novel knock-in humanized-mouse strain carrying a single-copy bacterial artificial chromosome (BAC). We also documented, for the first time, the expression pattern of the human BAC, using an NR2E1-lacZ reporter strain. Unexpectedly, cerebrum and olfactory bulb hypoplasia, hallmarks of the Nr2e1-null phenotype, were not fully corrected in animals harboring one functional copy of human NR2E1. These results correlated with an absence of NR2E1-lacZ reporter expression in the dorsal pallium of embryos and proliferative cells of adult brains. Surprisingly, retinal histology and electroretinograms demonstrated complete correction of the retina-null phenotype. These results correlated with appropriate expression of the NR2E1-lacZ reporter in developing and adult retina. We conclude that the human BAC contained all the elements allowing correction of the mouse-null phenotype in the retina, while missing key regulatory regions important for proper spatiotemporal brain expression. This is the first time a separation of regulatory mechanisms governing NR2E1 has been demonstrated. Furthermore, candidate genomic regions controlling expression in proliferating cells during neurogenesis were identified.

Elevated sedimentation on coral reefs adjacent to a beach nourishment project.

An increasingly common method to restore eroding beaches is nourishment, a process by which lost sand is replaced with terrestrial or offshore sediments to widen beaches. The southeastern Florida coastline contains shore-parallel coral reef communities adjacent to eroding beaches. Scleractinian corals and other reef-associated organisms are known to demonstrate sensitivity to elevated sedimentation levels. Sediment traps were used to examine spatio-temporal sedimentation patterns and assess the effects of nourishment (dredge and fill) activities. Several environmental variables correlated with among-site spatial variability of sediment parameters. Intra-annual variability correlated with wind velocity and direction. Nourishment activities showed localized effects, with sites in close proximity to dredging areas exhibiting significantly higher collection rates and lower percent fines than control sites. A regional increase in sedimentation occurred while nourishment activities were ongoing. Due to concurrent impacts of hurricanes, only one during-construction sampling interval revealed substantially higher collection rates relative to corresponding pre-construction sampling intervals.

Next generation tools for high-throughput promoter and expression analysis employing single-copy knock-ins at the Hprt1 locus.

We have engineered a set of useful tools that facilitate targeted single copy knock-in (KI) at the hypoxanthine guanine phosphoribosyl transferase 1 (Hprt1) locus. We employed fine scale mapping to delineate the precise breakpoint location at the Hprt1(b-m3) locus allowing allele specific PCR assays to be established. Our suite of tools contains four targeting expression vectors and a complementing series of embryonic stem cell lines. Two of these vectors encode enhanced green fluorescent protein (EGFP) driven by the human cytomegalovirus immediate-early enhancer/modified chicken beta-actin (CAG) promoter, whereas the other two permit flexible combinations of a chosen promoter combined with a reporter and/or gene of choice. We have validated our tools as part of the Pleiades Promoter Project (http://www.pleiades.org), with the generation of brain-specific EGFP positive germline mouse strains.

Assessing the accuracy of acoustic seabed classification for mapping coral reef environments in South Florida (Broward County, USA)

The Atlantic coast of Broward County, Florida (USA) is paralleled by a series of progressively deeper, shore-parallel coral reef communities. Two of these reef systems are drowned early Holocene coral reefs of 5 ky and 7 ky uncorrected radiocarbon age. Despite the case of access to these reefs, and their major contribution to the local economy, accurate benthic habitat maps of the area are not available. Ecological studies have shown that different benthic communities (i.e. communities composed of different biological taxa) exist along several spatial gradients on all reefs. Since these studies are limited by time and spatial extent, acoustic surveys with the QTCView V bottom classification system based on a 50 kHz transducer were used as an alternative method of producing habitat maps. From the acoustic data of a 3.1 km(2) survey area, spatial prediction maps were created for the area. These were compared with habitat maps interpreted from in situ data and Laser Airborne Depth Sounder (LADS) bathymetry, in order to ground-truth the remotely sensed data. An error matrix was used to quantitatively determine the accuracy of the acoustically derived spatial prediction model against the maps derived from the in situ and LADS data sets. Confusion analysis of 100 random points showed that the system was able to distinguish areas of reef from areas of rubble and sand with an overall accuracy of 61%. When asked to detect more subtle spatial differences, for example, those between distinct reef communities, the classification was only about 40% accurate. We discuss to what degree a synthesis of acoustic and in situ techniques can provide accurate habitat maps in coral reef environments, and conclude that acoustic methods were able to reflect the spatial extent and composition of at least three different biological communities.

Effect of dietary calcium and vitamin D3 on calcium and phosphorus retention in white Pekin ducklings.

Higher concentrations of Ca in the diet may decrease phytate-phosphorus hydrolysis because of chelation of Ca with the phytin molecule. In experiment 1, drakes were fed 0.74, 0.85, 0.95, or 1.11% Ca (analyzed) from 7 to 18 d of age (6 birds/cage, 8 cages/diet). Intestinal mucosa was collected at 18 d of age from birds fed 0.74 and 1.11% Ca for determination of intestinal phytase activity. In experiment 1, 17 d BW gain and feed consumption exhibited a quadratic response to increasing concentrations of Ca and were found to be maximal for ducks fed the 0.95% Ca diet. Toe ash percentage (18 d) had a quadratic response to increasing concentrations of Ca with a maximal response for birds fed the 0.85% Ca diet. Increasing dietary Ca did not affect P retention from 15 to 17 d of age or intestinal phytase activity and brush border vesicle Ca concentration. A positive correlation was found between the Vmax and the Ca concentration within the vesicles (r = 0.59, P < 0.02), suggesting that the vesicle Ca concentration did not negatively affect the kinetics of the phytase assay. In experiment 2, drakes were fed 0.6, 0.8, 1.0, or 1.2% Ca (formulated) with 826 or 8,260 ICU/kg of vitamin D3 from 0 to 13 d of age. There was no response to increasing concentrations of Ca for performance characteristics or bone ash measurements.

The effects of copper on the efficacy of phytase, growth, and phosphorus retention in broiler chicks.

Copper is often added to broiler diets at prophylactic concentrations as an antimicrobial despite purported chelation with and reduced utilization of phytin phosphorus. Therefore, male chicks were fed 0, 62.5, 125, 250, or 375 ppm Cu from Cu sulfate in combination with 600 phytase units (FTU)/kg phytase from 9 to 22 d of age (6 cages/diet, 8 birds/cage). Nonphytate phosphorus (NPP) and Ca were formulated to 0.2 and 0.7% of the diet, respectively. Three additional control diets were formulated to contain 0.27, 0.34, and 0.40% NPP, each with 0.7% Ca. Birds fed increasing concentrations of Cu with 600 FTU phytase/kg had linear reductions in performance characteristics (P < or = 0.05). Birds fed increasing concentrations of Cu with 600 FTU phytase/kg had linear increases in toe ash percentage (P < or = 0.027), but tibia ash percentage was not affected (P > 0.05). Birds fed increasing Cu concentrations with 600 FTU phytase/kg had linear reductions in apparent P retention as a percentage of total P (P < or = 0.0005). Supplementation with increasing concentrations of Cu to a diet containing 600 FTU phytase/kg resulted in decreases in 21 d BW, BW gain, feed consumption, feed conversion, tibia and toe ash weights, and apparent P retention as a percentage of total P. In this experiment, Cu supplementation did not reduce the efficacy of phytase (i.e., improvement in apparent P retention with phytase supplementation) but did decrease apparent P retention, BW gain, feed consumption, feed conversion, and tibia ash and toe ash weights.

Effects of copper source on phosphorus retention in broiler chicks and laying hens.

Copper sulfate is often added to broiler and laying hen diets at prophylactic dosages due to its antimicrobial and growth promoting effects despite reduced P digestibility, whereas P use from other Cu sources is unknown. Therefore, male broiler chicks were fed diets containing 0 or 250 ppm Cu from Cu sulfate (Cu SUL), Cu citrate (Cu CIT), Cu lysinate (Cu LYS), or CuCl from 9 to 22 d of age (8 cages/diet, 6 birds/cage) to determine the effect of each Cu source on performance characteristics, bone mineralization, and P retention. Body weight gain was not different among treatments (P > 0.05). Supplementation with 250 ppm Cu from Cu LYS resulted in chicks having greater toe and tibia ash weights as compared with chicks fed Cu SUL (P < or = 0.05) but was not significantly different from those of birds fed Cu CL, Cu CIT, and 0 ppm Cu diets. Supplementation with Cu LYS resulted in birds with greater toe ash percentage as compared with birds fed Cu CIT, Cu SUL, and the 0 ppm Cu diets (P < or = 0.05) but was not significantly different than those of birds fed the CuCl diet. Birds fed the Cu LYS diet had greater tibia ash percentage as compared with birds fed Cu SUL and 0 ppm Cu diets (P < or = 0.05) but were not significantly different than birds fed the Cu CL or Cu CIT diet. Supplementation with 250 ppm Cu SUL or Cu CIT reduced apparent P retention by 0.029 and 0.053 percentage-units of the diet, respectively (P < or = 0.05) as compared with the 0 ppm diet; whereas the apparent P retention when 250 ppm Cu LYS or Cu CL was fed was not different from the 0 ppm Cu diet (P > 0.05). Feeding of different Cu sources in a subsequent experiment had no influence on P retention in laying hens (P > 0.05). In conclusion, supplementation with 250 ppm Cu from Cu CIT or Cu SUL resulted in decreased apparent P retention. Supplementation with 250 ppm Cu CL or Cu LYS, however, improved apparent P retentions as compared with Cu CIT or Cu SUL.

Evaluation and validation of commercially available enzyme-linked immunosorbent assays (ELISAs) specific for atrazine, chlorpyrifos, and diazinon in aqueous phase.

The performance of commercially available microtiter plate enzyme-linked immunosorbent assays (ELISA) kits specific for the determination of triazines (atrazine), chlorpyrifos, and diazinon was evaluated for sensitivity, intra-assay repeatability, and accuracy using samples of known concentration in aqueous solution. Mean percent recovery values were not significantly different among concentrations for diazinon (One-way parametric ANOVA, P=0.46, n=72). However, mean percent recovery values were significantly different among concentrations for both atrazine and chlorpyrifos analyses (One-way parametric ANOVA, P<0.0001, n=36 for both analyses), and were highly dependent on concentrations for chlorpyrifos (% recovery=-0.155 (concentration)+238.448, r(2)=0.91, P<0.0001, n=36). All methods demonstrated a high degree of statistical separation between readings at various concentrations (One-way parametric ANOVA followed by Student-Neuman-Keuls (SNK) multiple range test, P<0.0001 for all analyses) and a close correlation between known concentrations and concentrations derived from ELISA for all three analytes (diazinon, r=0.985, P<0.0001, n=72; atrazine r=0.967, P<0.0001, n=36; chlorpyrifos r=0.947, P<0.0001, n=36). Statistical comparisons between known concentrations and concentrations derived from ELISAs showed that diazinon values were significantly (P<0.01, n=12 per concentration level) overestimated for all concentration levels. Chlorpyrifos concentrations were significantly (P<0.01, n=6 per concentration level) overestimated at lower concentrations and significantly (P<0.01, n=6 per concentration level) underestimated at higher concentrations. ELISA-derived atrazine concentrations were statistically similar to known concentrations for most concentration levels (P>0.05, n=6 per concentration level). Results indicate that ELISA kits are excellent for screening purposes, although consistent overestimation of ELISA for diazinon at all concentration levels and chlorpyrifos at lower concentrations levels must be resolved before the kits can be used routinely for regulatory compliance monitoring.

Microengineering as a tool to study substratum modulation and cell behaviour.

This research is an investigation of the means by which geometrical parameters (e.g. area and shape) and various surface attributes (materials and surface finish) of microengineered structures can modulate cellular response. This is based on biological observations indicating that: (i) the response of tissue cells to injury is determined by the net signal transduction response elicited by soluble regulatory molecules (e.g. cytokines), (ii) common matrix constituents (e.g. collagen) directly affect cell behaviour by the same signal transduction mechanisms mediating cytokine bioactivity, (iii) cellular response to cytokines is modulated by the precise nature of the extracellular matrix to which the target cells are adherent, including its biochemical composition and physical structure.

Giant renal oncocytoma.

We report the largest renal oncocytoma excised at the initial presentation and the second largest renal oncocytoma in published reports. Despite a tendency for renal oncocytomas to be relatively small and asymptomatic compared with renal cell carcinomas, these lesions cannot be reliably differentiated preoperatively. The variable nature of presentation and overlap of radiographic characteristics between these lesions complicates their clinical differentiation. The present case illustrates the difficulty in the preoperative diagnosis of even very large, enhancing renal masses and reinforces the inclusion of renal oncocytoma in the differential diagnosis of these lesions.