Optimal Timing for Assessment of Tumor Response to Neoadjuvant Chemoradiation in Patients With Rectal Cancer: Do All Patients Benefit From Waiting Longer Than 6 Weeks?

Purpose: To estimate the metabolic activity of rectal cancers at 6 and 12 weeks after completion of chemoradiation therapy (CRT) by 2-[fluorine-18] fluoro-2-deoxy-D-glucose-labeled positron emission tomography/computed tomography ([18 FDG] PET/CT) imaging and correlate with response to CRT. Methods and Materials: Patients with cT2-4N0-2M0 distal rectal adenocarcinoma treated with long-course neoadjuvant CRT (54 Gy, 5-fluouracil-based) were prospectively studied (ClinicalTrials. org identifier NCT00254683). All patients underwent 3 PET/CT studies (at baseline and 6 and 12 weeks fromCRT completion). Clinical assessment was at 12 weeks. Maximal standard uptakevalue (SUVmax) of the primary tumor wasmeasured and recorded at eachPET/CTstudy after 1 h (early) and3 h (late) from 18 FDGinjection. Patientswith an increase in early SUVmax between 6 and 12 weeks were considered " bad" responders and the others as "good" responders. Results: Ninety-one patients were included; 46 patients (51%) were "bad" responders, whereas 45 (49%) patients were " good" responders. " Bad" responders were less likely to develop complete clinical response (6.5% vs. 37.8%, respectively; PZ. 001), less likely to develop significant histological tumor regression (complete or near-complete pathological response; 16% vs. 45%, respectively; PZ. 008) and exhibited greater final tumor dimension (4.3cmvs. 3.3cm; PZ. 03). Decrease between early (1 h) and late (3 h) SUVmax at 6-week PET/CTwas a significant predictor of " good" response (accuracy of 67%). Conclusions: Patients who developed an increase in SUVmax after 6 weeks were less likely to develop significant tumor downstaging. Early-late SUVmax variation at 6-week PET/CT may help identify these patients and allow tailored selection of CRT-surgery intervals for individual patients. (C) 2012 Elsevier Inc.

Absence of inactivating mutations and deletions in the DMRT1 and FGF9 genes in a large cohort of 46,XY patients with gonadal dysgenesis

Despite advances in our understanding of the mechanisms involved in sex determination and differentiation, the specific roles of many genes in these processes are not completely understood in humans. Both DMRT1 and FGF9 are among this group of genes. Dmrt1 controls germ cell differentiation, proliferation, migration and pluripotency and Sertoli cell proliferation and differentiation. Fgf9 has been considered a critical factor in early testicular development and germ cell survival in mice. We screened for the presence of DMRT1 and FGF9 mutations in 33 patients with 46,XY gonadal dysgenesis. No deletions in either DMRT1 or FGF9 were identified using the MLPA technique. Eight allelic variants of DMRT1 were identified, and in silico analysis suggested that the novel c.968-15insTTCTCTCT variant and the c.774G>C (rs146975077) variant could have potentially deleterious effects on the DMRT1 protein. Nine previously described FGF9 allelic variants and six different alleles of the 3' UTR microsatellite were identified. However, none of these DMRT1 or FGF9 variants was associated with increased 46,XY gonadal dysgenesis. In conclusion, our study suggests that neither DMRT1 nor FGF9 abnormalities are frequently involved in dysgenetic male gonad development in patients with non-syndromic 46,XY disorder of sex development. (C) 2012 Published by Elsevier Masson SAS.

Lasiodiplodan, an exocellular (1 -> 6)-beta-d-glucan from Lasiodiplodia theobromae MMPI: production on glucose, fermentation kinetics, rheology and anti-proliferative activity

Lasiodiplodan, an exopolysaccharide of the (1 -> 6)-beta-d-glucan type, is produced by Lasiodiplodia theobromae MMPI when grown under submerged culture on glucose. The objective of this study was to evaluate lasiodiplodan production by examining the effects of carbon (glucose, fructose, maltose, sucrose) and nitrogen sources (KNO3, (NH4)(2)SO4, urea, yeast extract, peptone), its production in shake flasks compared to a stirred-tank bioreactor, and to study the rheology of lasiodiplodan, and lasiodiplodan's anti-proliferative effect on breast cancer MCF-7 cells. Although glucose (2.05 +/- A 0.05 g L-1), maltose (2.08 +/- A 0.04 g L-1) and yeast extract (2.46 +/- A 0.06 g L-1) produced the highest amounts of lasiodiplodan, urea as N source resulted in more lasiodiplodan per unit biomass than yeast extract (0.74 +/- A 0.006 vs. 0.22 +/- A 0.008 g g(-1)). A comparison of the fermentative parameters of L. theobromae MMPI in shake flasks and a stirred-tank bioreactor at 120 h on glucose as carbon source showed maximum lasiodiplodan production in agitated flasks (7.01 +/- A 0.07 g L-1) with a specific yield of 0.25 +/- A 0.57 g g(-1) and a volumetric productivity of 0.06 +/- A 0.001 g L-1 h(-1). A factorial 2(2) statistical design developed to evaluate the effect of glucose concentration (20-60 g L-1) and impeller speed (100-200 rpm) on lasiodiplodan production in the bioreactor showed the highest production (6.32 g L-1) at 72 h. Lasiodiplodan presented pseudoplastic behaviour, and the apparent viscosity increased at 60A degrees C in the presence of CaCl2. Anti-proliferative activity of lasiodiplodan was demonstrated in MCF-7 cells, which was time- and dose-dependent with an IC50 of 100 mu g lasiodiplodan mL(-1).

Is waist-to-height ratio a useful indicator of cardio-metabolic risk in 6-10-year-old children?

Background: Childhood obesity is a public health problem worldwide. Visceral obesity, particularly associated with cardio-metabolic risk, has been assessed by body mass index (BMI) and waist circumference, but both methods use sex-and age-specific percentile tables and are influenced by sexual maturity. Waist-to-height ratio (WHtR) is easier to obtain, does not involve tables and can be used to diagnose visceral obesity, even in normal-weight individuals. This study aims to compare the WHtR to the 2007 World Health Organization (WHO) reference for BMI in screening for the presence of cardio-metabolic and inflammatory risk factors in 6–10-year-old children. Methods: A cross-sectional study was undertaken with 175 subjects selected from the Reference Center for the Treatment of Children and Adolescents in Campos, Rio de Janeiro, Brazil. The subjects were classified according to the 2007 WHO standard as normal-weight (BMI z score > −1 and < 1) or overweight/obese (BMI z score ≥ 1). Systolic blood pressure (SBP), diastolic blood pressure (DBP), fasting glycemia, low-density lipoprotein (LDL), high-density lipoprotein (HDL), triglyceride (TG), Homeostatic Model Assessment – Insulin Resistance (HOMA-IR), leukocyte count and ultrasensitive C-reactive protein (CRP) were also analyzed. Results: There were significant correlations between WHtR and BMI z score (r = 0.88, p < 0.0001), SBP (r = 0.51, p < 0.0001), DBP (r = 0.49, p < 0.0001), LDL (r = 0.25, p < 0.0008, HDL (r = −0.28, p < 0.0002), TG (r = 0.26, p < 0.0006), HOMA-IR (r = 0.83, p < 0.0001) and CRP (r = 0.51, p < 0.0001). WHtR and BMI areas under the curve were similar for all the cardio-metabolic parameters. A WHtR cut-off value of > 0.47 was sensitive for screening insulin resistance and any one of the cardio-metabolic parameters. Conclusions: The WHtR was as sensitive as the 2007 WHO BMI in screening for metabolic risk factors in 6-10-year-old children. The public health message “keep your waist to less than half your height” can be effective in reducing cardio-metabolic risk because most of these risk factors are already present at a cut point of WHtR ≥ 0.5. However, as this is the first study to correlate the WHtR with inflammatory markers, we recommend further exploration of the use of WHtR in this age group and other population-based samples.