Quantification of the anti-neoplastic polyacetylene falcarinol from carrots in human serum by LC-MS/MS.

Falcarinol is a polyacetylene which is found in carrots and known to have anti-neoplastic properties in rodents. Research in the bioactivity of falcarinol in humans require methods for quantification of falcarinol in human serum. Here we report the development of an LC-MS/MS method and its use to measure serum falcarinol concentrations in humans following intake of a carrot product. Falcarinol was measured by LC-MS/MS using the m/z 268 to m/z 182 mass transition. Six calibrator levels (0.2-20 ng/mL) and 3 control levels (0.4, 2 and 8 ng/mL) were prepared by addition of falcarinol to human serum pools. Linearity of the developed method was good with a mean R2 of 0.9942. Within-day, between-day and total coefficients of variation were 6.9-13.1%, 4.1-5.0% and 8.1-14.0%, respectively. The limits of detection and quantitation were 0.1 and 0.2 ng/mL, respectively, matrix effects 84.2%, recovery 101.4-105.4% and carry-over -0.24-0.07%. Serum falcarinol concentrations were measured in 18 healthy volunteers prior to and at 9 time-points following intake of a carrot product. Falcarinol concentrations peaked at the 1-hour time-point after intake in 15 out of 18 volunteers and declined according to a single exponential decay function with an aggregate t½ of 1.5 h. In conclusion, an LC-MS/MS method for quantification of falcarinol in human serum with acceptable performance was developed and used to measure falcarinol concentrations following intake of a carrot product.

Can coffee or chewing gum decrease transit times in Colon capsule endoscopy? A randomized controlled trial.

BACKGROUND: A high rate of complete colon capsule endoscopy (CCE) investigations is required for a more widespread use of CCE. The objective of this study was to assess if coffee or chewing gum can increase excretion of the colon capsule within battery life time (excretion rate). METHODS: One hundred eighty six screening participants with a positive immunochemical fecal occult blood test were included in this single-centre randomized controlled trial with blinding of the investigators to the randomization. Participants received instant coffee, chewing gum or nothing in addition to the standard bowel preparation. RESULTS: The intention was to include 57 participants in the coffee group, 61 in the chewing gum group and 60 in the control group, on 8 participants data were missing. A total of 165 participants were included in a per protocol analysis. Exclusion was due to not receiving the allocated intervention (8 coffee, 4 chewing gum) and technical failure of the capsule (1 coffee). The excretion rate was 58% in the coffee group (n = 48), 63% in the chewing gum group (n = 57) and 55% in the control group (n = 60, p > 0.2). Transit times were similar in all groups. The excretion rate was low in participants who had transit times over 10 h (14%). A strong correlation was found between adequate cleansing and excretion of the capsule. There were no serious adverse events related to the interventions or CCE investigations. CONCLUSIONS: Chewing gum and coffee did not improve excretion rate in this study. An effect of chewing gum could not be proven, possibly due to sample size. Since chewing gum might improve excretion rates, is cheap and has no known side effects, it needs to be considered in future bowel preparation trials for CCE. TRIAL REGISTRATION: NCT02303756 , registered on December 1st 2014.

Dietary polyacetylenes, falcarinol and falcarindiol, isolated from carrots prevents the formation of neoplastic lesions in the colon of azoxymethane-induced rats.

Falcarinol (FaOH) and falcarindiol (FaDOH) are found in many food plants of the Apiaceae family. Carrots are a major dietary source of these polyacetylenes. Feeding azoxymethane (AOM)-induced rats with carrots and purified FaOH have previously been shown to inhibit neoplastic transformations in the colon. FaOH and FaDOH have also shown to have a synergistic effect in vitro, resulting in a significant increased cytotoxic activity. Based on these findings the antineoplastic effect of FaOH and FaDOH (purity > 99%) was investigated in the AOM-induced rat model. Twenty rats received rat diet containing 7 µg FaOH per g feed and 7 µg FaDOH per g feed and 20 rats were controls receiving only rat diet. Then carcinogenesis was induced in all 40 rats with the carcinogen AOM. All animals received the designated diet for 2 weeks before AOM induction and continued on the designated diet throughout the experiment. Rats were euthanized 18 weeks after the first AOM injection and macroscopic polyp/cancers were measured, harvested and stained for histology. The difference in sizes of aberrant crypt foci (ACF) were analysed in a Wilcoxon rank sum test, in which the median number of small ACF was 218 in controls and 145 in polyacetylene treated rats (P < 0.001). Fifteen control rats and 8 treated rats had macroscopic tumors (P = 0.027). The number of tumors larger than 3 mm were 6 and 1 in control and treated rats, respectively (P = 0.032). In conclusion dietary supplements with FaOH and FaDOH reduced the number of neoplastic lesions as well as the growth rate of the polyps suggesting a preventive effect of FaOH and FaDOH on the development of colorectal cancer.

Long-term results of a phase II trial of high-dose radiotherapy (60 Gy) and UFT/l-leucovorin in patients with non-resectable locally advanced rectal cancer (LARC).

BACKGROUND: Preoperative radiochemotherapy is a cornerstone in patients with non- resectable locally advanced rectal cancer (LARC). To improve outcome (number of R0 resections and survival) high-dose radiotherapy (RT) was combined with oral UFT/l-leucovorin to allow tumour regression before radical intended surgery. METHODS: Pelvic RT was delivered with megavoltage photons using a 5 field technique. RT was CT-based, given 5 days a week through one posterior field and two lateral fields (48.6 Gy/27 fractions) to encompass the primary tumour and the regional lymph nodes. In addition, the tumour bed received a concurrent boost (5.4 Gy/27 fractions) and a final boost (6 Gy/3 fractions); thus GTV received 60 Gy/30 fractions. Concurrent with RT patients received a daily dose of oral UFT 300 mg/m(2) plus l-leucovorin 22.5 mg 5/7 days (divided in three doses). RESULTS: From September 2000 to November 2004, 52 patients (median age 60 years (32-83); median PS 0 (0-2)) with LARC (36 primary, 16 recurrent) were included in this phase II study. All but three patients received the planned 60 Gy, median duration of RT was 42 days (25-49). Toxicity was very modest; only four patients had a dose reduction of UFT. No hematological toxicity of clinical significance was seen. Non-hematological toxicity grade 1 (GI-toxicity, fatigue and/or dysuria) was frequently observed but only four patients experienced grade 3 toxicity (diarrhoea and/or nausea/vomiting). Forty patients (77%) were operated (30 R0, 5 R1, 5 R2) median 55 days (27-112) after completion of RT. Seven (13%) patients had a pathological complete response (pCR). Thirty-one patients (60%) died after median 25.4 months (1.6-45.2 months). Twenty-one patients (40%) are still alive June 2007. CONCLUSIONS: Preoperative high-dose RT and concomitant UFT produces major regression in most patients with non-resectable LARC and thus a good chance of cure.

[New treatment strategies for patients with primary non-resectable rectal cancer]. / Ny behandlingsstrategi for patienter med primaer, ikkeresektabel rectumcancer.

INTRODUCTION: Patients with locally advanced rectal cancer (LARC) have a poor prognosis. Preoperative radiotherapy may shrink the tumour and make subsequent resection possible. The use of modern principles of preoperative radiotherapy in combination with chemotherapy and an active surgical attitude increases the chance for radical surgery and cure. MATERIALS AND METHODS: A single-institution, prospective evaluation of a new treatment strategy in patients with LARC was done. RESULTS: From 1998 to 2000, 20 patients with LARC were treated with high-dose radiochemotherapy (60 Gy and chemotherapy, UFT/leucovorin), and resectability was evaluated four to six weeks after termination of radiochemotherapy. Sixty percent of the patients subsequently had microscopic radical surgery. CONCLUSION: Patients with LARC should preferably be treated with high-dose preoperative radiotherapy in combination with chemotherapy. Evaluation of resectability should be performed at least four weeks after termination of radiotherapy. This strategy, in combination with modern surgical techniques, increases the probability of success of radical surgery and cure.