Serum glutathione transferase does not respond to indole-3-carbinol: A pilot study.

BACKGROUND: Despite the well recognized protective effect of cruciferous vegetables against various cancers, including human colorectal cancers, little is known about how this effect is conferred. It is thought that some phytochemicals found only in these vegetables confer the protection. These compounds include the glucosinolates, of which indole-3-carbinol is one. They are known to induce carcinogen-metabolizing (phase II) enzymes, including the glutathione S-transferase (GST) family. Other effects in humans are not well documented. We wished to assess the effect of indole-3-carbinol on GST enzymes. METHODS: We carried out a placebo-controlled human volunteer study. All patients were given 400 mg daily of indole-3-carbinol for three months, followed by placebo. Serum samples were tested for the GSTM1 genotype by polymerase chain reaction. Serum GST levels were assessed using enzyme-linked immunosorbent assay and Western Blot methodologies. RESULTS: Forty-nine volunteers completed the study. GSTM1 genotypes were obtained for all but two volunteers. A slightly greater proportion of volunteers were GSTM1-positive, in keeping with the general population. GST was detected in all patients. Total GST level was not affected by indole-3-carbinol dosing compared with placebo. Although not statistically significant, the GSTM1 genotype affected the serum GST level response to indole-3-carbinol. CONCLUSION: Indole-3-carbinol does not alter total serum GST levels during prolonged dosing.

Putative mechanisms of action for indole-3-carbinol in the prevention of colorectal cancer.

BACKGROUND: Multiple factors are known to contribute to the development of cancer and numerous agents have been shown to confer some protection. Diets high in vegetables, especially cruciferous vegetables (broccoli, Brussels sprouts, cabbage etc.) provide such protection. OBJECTIVE: To define the phytonutrients within this group of vegetables and how their chemoprotective properties might be conferred. METHODS: Cruciferous vegetables provide the only human dietary source of a class of phytonutrients, the glucosinolates. The glucosinolate breakdown products, which include indole-3-carbinol and sulforaphane, have demonstrated various anticancer actions in laboratory studies. We give a brief overview of current understanding of the chemopreventive pathways for indole-3-carbinol in various human cancers and how this may relate, in particular, to colorectal cancer; the supporting evidence; and our opinion of its anticancer properties. The review is limited by the lack of bioavailability data in humans. RESULTS: Indole-3-carbinol interacts with a multitude of intracellular processes, which may halt tumourgenesis and induce apoptosis.

Surgeon and hospital volume and the management of colorectal cancer patients in Australia.

BACKGROUND: The evidence for a relationship between patient outcomes and clinician and hospital volume is increasing. The National Colorectal Cancer Care Survey was undertaken to determine the management patterns in Australia for individuals newly diagnosed with colorectal cancer in a 3 month period in the year 2000. METHODS: All new cases of colorectal cancer registered at each Australian State Cancer Registry were entered into the survey. This generated a questionnaire that was sent to the treating surgeon. Chi-squared tests and logistic regression analyses were used to determine levels of statistical significance. RESULTS: Of 2,383 surgical questionnaires generated, 2,015 (85%) were completed. The majority (58%) of surgeons treated one or two patients with colorectal cancer over the 3 months of the survey. There was variation across surgeon cohorts for preoperative measures including the use of deep vein thrombosis prophylaxis. Patients seen by low volume surgeons were most likely to be given a permanent stoma (P < 0.0001). Patients with rectal cancer who were operated on by high volume surgeons were significantly more likely to receive a colonic pouch (P < 0.0001). CONCLUSION: This nationwide population-based survey of the treatment of colorectal cancer patients suggests that the delivery of care by surgeons (the majority) who treat patients with rectal cancer infrequently should be evaluated.

Management of colorectal cancer patients in Australia: the National Colorectal Cancer Care Survey.

BACKGROUND: The National Colorectal Cancer Care Survey was undertaken to determine the management patterns for individuals newly diagnosed with colorectal cancer in Australia. METHODS: Between 1 February and 30 April 2000, all new cases of colorectal cancer registered at each Cancer Registry within Australia were entered into the survey. This generated a questionnaire that was sent to the treating surgeons. Chi-squared and logistic regression analyses were used to determine levels of statistical significance for the various comparisons of interest. RESULTS: Of 2383 surgical questionnaires generated, 2015 (85%) were completed. A total of 1911 patients (95% of those who responded to the questionnaire) had an operation. Of the 86 guidelines for the management of colorectal cancer published by the National Health and Medical Research Council, the survey allowed for comparison between 18 of these, which covered a spectrum of surgical management. Thromboembolic prophylaxis was given to 1843 patients (96.4%) undergoing surgery. Prophylactic antibiotics were commonly used, but there appear to be issues regarding the best regimen to use. Curative resections were carried out in 1563 patients (81.8%), with anterior resections being the most commonly performed procedure. Adjuvant therapy was regularly used, but not all eligible patients were offered such treatment. CONCLUSION: With the considerable resources required to develop clinical practice guidelines, studies like this are essential to monitor the impact of the guidelines. To ensure that the guidelines are in line with current evidence, regular reviews of the guideline recommendations are required.

In the beginning there was colectomy: current surgical options in familial adenomatous polyposis.

Multiple colonic polyps, almost guaranteed colorectal cancer by the age of forty-five and an increased risk of non-colonic cancers characterise the autosomal dominant condition Familial Adenomatous Polyposis (FAP) 1. The patients and families faced with such a diagnosis present many difficult management challenges, both surgical and non-surgical. We discuss the current surgical options for treatment of the more significant manifestations of FAP arising in the colorectum and duodenum as well as desmoid disease.

The effect of indole-3-carbinol and sulforaphane on a prostate cancer cell line.

BACKGROUND: Cruciferous vegetable consumption is inversely related to the incidence of prostate cancer. We examined the effect of indole-3-carbinol (I3C) and of sulforaphane (constituents of cruciferous vegetables) on cell proliferation of a PC-3 prostate cancer cell line, in order to observe if an inhibitory effect might be detected in vitro. METHODS: PC-3 prostate cancer cells were cultured in 96-well microtitre plates. Indole-3-carbinol concentrations ranging from 0.1 mmol/L to 0.8 mmol/L or sulforaphane concentrations ranging from 0.01 mmol/L to 0.06 mmol/L were added to the wells. Cell proliferation was measured by colorimetric assay and results were based on the mean value of triplicate experiments. Data are -presented as medians and interquartile ranges and were analysed using the Mann-Whitney U-test. RESULTS: Cell proliferation in PC-3 prostate cancer cells was significantly inhibited by I3C and sulforaphane at media concentrations of 0.2 mmol/L and 0.02 mmol/L, respectively. CONCLUSION: Both compounds inhibited the proliferation of prostate cancer cells in a dose-dependent manner. These findings may help explain the observed protective effect of cruciferous vegetables in relation to prostate cancer.