D3 is approximately 87% more potent in raising and maintaining serum 25(OH)D concentrations and produces 2- to 3-fold greater storage of vitamin D than does equimolar D2. For neither was there evidence of sequestration in fat, as had been postulated for doses in this range. Given its greater potency and lower cost, D3 should be the preferred treatment option when correcting vitamin D deficiency.

This article appears in The Journal of Clinical Endocrinology & Metabolism, published December 22, 2010, 10.1210/jc.2010-2230

Background In recent decades there has been growing interest in the use of volatile organic compounds (VOCs) in exhaled breath as biomarkers for the diagnosis of multiple variants of cancer. This review aimed to evaluate the diagnostic accuracy and current status of VOC analysis in exhaled breath for the detection of cancer in the digestive tract. Methods PubMed and the Cochrane Library database were searched for VOC analysis studies, in which exhaled air was used to detect gastro-oesophageal, liver, pancreatic, and intestinal cancer in humans, Quality assessment was performed using the QUADAS-2 criteria. Data on diagnostic performance, VOCs with discriminative power, and methodological information were extracted from the included articles. Results Twenty-three articles were included (gastro-oesophageal cancer n = 14, liver cancer n = 1, pancreatic cancer n = 2, colorectal cancer n = 6). Methodological issues included different modalities of patient preparation and sampling and platform used. The sensitivity and specificity of VOC analysis ranged from 66.7 to 100 per cent and from 48.1 to 97.9 per cent respectively. Owing to heterogeneity of the studies, no pooling of the results could be performed. Of the VOCs found, 32 were identified in more than one study. Nineteen were reported as cancer type-specific, whereas 13 were found in different cancer types. Overall, decanal, nonanal, and acetone were the most frequently identified. Conclusion The literature on VOC analysis has documented a lack of standardization in study designs. Heterogeneity between the studies and insufficient validation of the results make interpretation of the outcomes challenging. To reach clinical applicability, future studies on breath analysis should provide an accurate description of the methodology and validate their findings.

B ackground: Current therapies for CLL/SLL have frequent toxicities, are non-curative, and several trials have demonstrated that early treatment of the disease doesn't result in longer overall survival. In high doses, both curcumin (CM), from turmeric, and vitamin D (VD) have been shown to be safe in multiple clinical trials of solid tumors. Curcumin was shown to disrupt CLL cell interactions with the microenvironment, induce apoptosis independent of DNA damage, and upregulate vitamin D receptor (VDR) in malignant lymphoid cells. We hypothesized that the combination of CM and VD is safe and active in CLL/SLL and would delay disease progression. Methods: This was an open-label phase II trial for previously untreated patients with asymptomatic,Rai stage 0-II CLL/SLL not currently meeting National CancerInstitute Working Group (NCI-WG) Criteria for treatment. All patients received 8 gm of CM and 10,000 IU of vitamin D3 (VD) orally daily. VD was started 1 week after CM and both agents were maintained for up to six 4-week cycles. The primary endpoint was the overall response rate (ORR) based on NCI-WG criteria. Secondary endpoints were event-free (EFS), overall survival (OS), and time to next treatment (TTNT). VD-25-OH and CM major metabolites; CM glucuronide (COG) and CM sulfate (COS), were measured in plasma by liquid chromatography-tandem mass spectrometry. Phosphorylated-NF-κB (nuclear factor kappa-light-chain-enhancer of activated B cells), a validated pharmacodynamic marker of CM activity, as well as VDR, were measured in CLL cells by flow cytometry. Results: A total of 35 patients (pts), 51% males, were accrued to the trial, 30 (86%) were evaluable for response. Median age was 60 years (range 45-80). Most had CLL (97%); 51% were Rai stage 0 and 49% were Rai stage 1. Cytogenetic abnormalities included del13q14 (37%), trisomy 12 (11%), del 11q22 (11%) and del 17p (3%); 20% had ZAP-70 levels >20%. Median number of cycles received was 5 (range 1-6) and treatment was well tolerated overall. The most frequent adverse effects (AE) were diarrhea/gastrointestinal upset in 69% of patients (14% were grade 3). No serious AEs were observed. Eighteen pts (51%) completed all 6 cycles of treatment; 10 (29%) withdrew consent, 4 (11%) discontinued treatment because of diarrhea, and 3 (9%) patients progressed on treatment. Best response was stable disease in 28/30 (93%) evaluable pts. After a median follow up of 29 months, EFS was 72.0% (95% CI 52.1 - 84.7%), 74.1% (95% CI 58.7-89.6%) had not started new CLL treatment, and OS was 100%. Median VD-25-OH levels were 28.75ng/ml (range 12.5-55.6) at baseline and 49.5 ng/ml (24.8-69) at 28 days. Median COG/COS levels were 15.8 (2.73-75)/6.71(0-33.5) and 18 (0-75.9)/7.21(0-35.2) ng/ml at 8 and 28 days, respectively. Flow cytometric analysis of CLL cells showed no significant change in VDR or Phosphorylated-NF-κB with CM-VD treatment. Conclusion: Curcumin and high-dose vitamin D combination is safe and well tolerated in patients with early stage CLL. Although no responses were seen, the majority of patients maintained stable disease on treatment. Longer follow up is planned on this study to determine long - term CLL progression rates of patients treated with CM-VD. Disclosures Afable: Eli Lilly: Employment. Lazarus:Pluristem Ltd.: Consultancy. Nagabhushanam:Sabinsa Corporation: Employment. Grote:BTR Group Inc: Employment. Kunati:Symrise AG: Employment.

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