Importance Cannabis and cannabinoid drugs are widely used to treat disease or alleviate symptoms, but their efficacy for specific indications is not clear.Objective To conduct a systematic review of the benefits and adverse events (AEs) of cannabinoids.Data Sources Twenty-eight databases from inception to April 2015. Study SelectionRandomized clinical trials of cannabinoids for the following indications: nausea and vomiting due to chemotherapy, appetite stimulation in HIV/AIDS, chronic pain, spasticity due to multiple sclerosis or paraplegia, depression, anxiety disorder, sleep disorder, psychosis, glaucoma, or Tourette syndrome. Data Extraction and SynthesisStudy quality was assessed using the Cochrane risk of bias tool. All review stages were conducted independently by 2 reviewers. Where possible, data were pooled using random-effects meta-analysis. Main Outcomes and MeasuresPatient-relevant/disease-specific outcomes, activities of daily living, quality of life, global impression of change, and AEs.Results A total of 79 trials (6462 participants) were included; 4 were judged at low risk of bias. Most trials showed improvement in symptoms associated with cannabinoids but these associations did not reach statistical significance in all trials. Compared with placebo, cannabinoids were associated with a greater average number of patients showing a complete nausea and vomiting response (47% vs 20%; odds ratio [OR], 3.82 [95% CI, 1.55-9.42]; 3 trials), reduction in pain (37% vs 31%; OR, 1.41 [95% CI, 0.99-2.00]; 8 trials), a greater average reduction in numerical rating scale pain assessment (on a 0-10-point scale; weighted mean difference [WMD], −0.46 [95% CI, −0.80 to −0.11]; 6 trials), and average reduction in the Ashworth spasticity scale (WMD, −0.12 [95% CI, −0.24 to 0.01]; 5 trials). There was an increased risk of short-term AEs with cannabinoids, including serious AEs. Common AEs included dizziness, dry mouth, nausea, fatigue, somnolence, euphoria, vomiting, disorientation, drowsiness, confusion, loss of balance, and hallucination. Conclusions and RelevanceThere was moderate-quality evidence to support the use of cannabinoids for the treatment of chronic pain and spasticity. There was low-quality evidence suggesting that cannabinoids were associated with improvements in nausea and vomiting due to chemotherapy, weight gain in HIV infection, sleep disorders, and Tourette syndrome. Cannabinoids were associated with an increased risk of short-term AEs.

Stem cells are clonogenic cells with self-renewal and differentiation properties, which may represent a major target for genetic damage leading to prostate cancer and benign prostatic hyperplasia. Stem cells remain poorly characterised because of the absence of specific molecular markers that permit us to distinguish them from their progeny, the transit amplifying cells, which have a more restricted proliferative potential. Human CD133 antigen, also known as AC133, was recently identified as a haematopoietic stem cell marker. Here we show that a small population (approximately 1%) of human prostate basal cells express the cell surface marker CD133 and are restricted to the α2β1hi population, previously shown to be a marker of stem cells in prostate epithelia (Collins, A. T., Habib, F. K., Maitland, N. J. and Neal, D. E. (2001). J. Cell Sci. 114, 3865-3872). α2β1hi/CD133+ cells exhibit two important attributes of epithelial stem cells: they possess a high in vitro proliferative potential and can reconstitute prostatic-like acini in immunocompromised male nude mice.

Background: The tumor-initiating capacity of many cancers is considered to reside in a small subpopulation of cells (cancer stem cells). We have previously shown that rare prostate epithelial cells with a CD133 + /α 2 β 1 hi phenotype have the properties of prostate cancer stem cells. We have compared gene expression in these cells relative to their normal and differentiated (CD133 -/ α 2 β 1 low ) counterparts, resulting in an informative cancer stem cell gene-expression signature.

BackgroundThis study has attempted to assess the effectiveness of quantitative faecal immunochemical tests (FIT) for triage of people presenting with lower abdominal symptoms, where a referral to secondary care for investigation of suspected colorectal cancer (CRC) is being considered, particularly when the 2-week criteria are not met.MethodsWe conducted a systematic review following published guidelines for systematic reviews of diagnostic tests. Twenty-one resources were searched up until March 2016. Summary estimates were calculated using a bivariate model or a random-effects logistic regression model.ResultsNine studies are included in this review. One additional study, included in our systematic review, was provided as ‘academic in confidence’ and cannot be described herein.When FIT was based on a single faecal sample and a cut-off of 10 μg Hb/g faeces, sensitivity estimates indicated that a negative result using either the OC-Sensor or HM-JACKarc may be adequate to rule out nearly all CRC; the summary estimate of sensitivity for the OC-Sensor was 92.1% (95% confidence interval, CI 86.9–95.3%), based on four studies (n = 4091 participants, 176 with CRC), and the only study of HM-JACKarc to assess the 10 μg Hb/g faeces cut-off (n = 507 participants, 11 with CRC) reported a sensitivity of 100% (95% CI 71.5–100%). The corresponding specificity estimates were 85.8% (95% CI 78.3–91.0%) and 76.6% (95% CI 72.6–80.3%), respectively.When the diagnostic criterion was changed to include lower grades of neoplasia, i.e. the target condition included higher risk adenoma (HRA) as well as CRC, the rule-out performance of both FIT assays was reduced.ConclusionsThere is evidence to suggest that triage using FIT at a cut-off around 10 μg Hb/g faeces has the potential to correctly rule out CRC and avoid colonoscopy in 75–80% of symptomatic patients.Systematic review registrationPROSPERO 42016037723Electronic supplementary materialThe online version of this article (doi:10.1186/s12916-017-0944-z) contains supplementary material, which is available to authorized users.

Motile prostate cancer cell lines express vimentin. In tissue sections, the presence of vimentin positive tumour cells correlated positively to poorly differentiated cancers and the presence of bone metastases.

Despite the discovery over 60 years ago by Huggins and Hodges [1] that prostate cancers respond to androgen deprivation therapy, hormone-refractory prostate cancer remains a major clinical challenge. There is now mounting evidence that solid tumours originate from undifferentiated stem cell-like cells coexisting within a heterogeneous tumour mass that drive tumour formation, maintain tumour homeostasis and initiate metastases. This review focuses upon current evidence for prostate cancer stem cells, addressing the identification and properties of both normal and transformed prostate stem cells.

BackgroundColorectal cancer (CRC) is the third most common cancer in the UK. Presenting symptoms that can be associated with CRC usually have another explanation. Faecal immunochemical tests (FITs) detect blood that is not visible to the naked eye and may help to select patients who are likely to benefit from further investigation.ObjectivesTo assess the effectiveness of FITs [OC-Sensor (Eiken Chemical Co./MAST Diagnostics, Tokyo, Japan), HM-JACKarc (Kyowa Medex/Alpha Laboratories Ltd, Tokyo, Japan), FOB Gold (Sentinel/Sysmex, Sentinel Diagnostics, Milan, Italy), RIDASCREEN Hb or RIDASCREEN Hb/Hp complex (R-Biopharm, Darmstadt, Germany)] for primary care triage of people with low-risk symptoms.MethodsTwenty-four resources were searched to March 2016. Review methods followed published guidelines. Summary estimates were calculated using a bivariate model or a random-effects logistic regression model. The cost-effectiveness analysis considered long-term costs and quality-adjusted life-years (QALYs) that were associated with different faecal occult blood tests and direct colonoscopy referral. Modelling comprised a diagnostic decision model, a Markov model for long-term costs and QALYs that were associated with CRC treatment and progression, and a Markov model for QALYs that were associated with no CRC.ResultsWe included 10 studies. Using a single sample and 10 µg Hb/g faeces threshold, sensitivity estimates for OC-Sensor [92.1%, 95% confidence interval (CI) 86.9% to 95.3%] and HM-JACKarc (100%, 95% CI 71.5% to 100%) indicated that both may be useful to rule out CRC. Specificity estimates were 85.8% (95% CI 78.3% to 91.0%) and 76.6% (95% CI 72.6% to 80.3%). Triage using FITs could rule out CRC and avoid colonoscopy in approximately 75% of symptomatic patients. Data from our systematic review suggest that 22.5–93% of patients with a positive FIT and no CRC have other significant bowel pathologies. The results of the base-case analysis suggested minimal difference in QALYs between all of the strategies; no triage (referral straight to colonoscopy) is the most expensive. Faecal immunochemical testing was cost-effective (cheaper and more, or only slightly less, effective) compared with no triage. Faecal immunochemical testing was more effective and costly than guaiac faecal occult blood testing, but remained cost-effective at a threshold incremental cost-effectiveness ratio of £30,000. The results of scenario analyses did not differ substantively from the base-case. Results were better for faecal immunochemical testing when accuracy of the guaiac faecal occult blood test (gFOBT) was based on studies that were more representative of the correct population.LimitationsOnly one included study evaluated faecal immunochemical testing in primary care; however, all of the other studies evaluated faecal immunochemical testing at the point of referral. Further, validation data for the Faecal haemoglobin, Age and Sex Test (FAST) score, which includes faecal immunochemical testing, showed no significant difference in performance between primary and secondary care. There were insufficient data to adequately assess FOB Gold, RIDASCREEN Hb or RIDASCREEN Hb/Hp complex. No study compared FIT assays, or FIT assays versus gFOBT; all of the data included in this assessment refer to the clinical effectiveness of individual FIT methods andnottheir comparative effectiveness.ConclusionsFaecal immunochemical testing is likely to be a clinically effective and cost-effective strategy for triaging people who are presenting, in primary care settings, with lower abdominal symptoms and who are at low risk for CRC. Further research is required to confirm the effectiveness of faecal immunochemical testing in primary care practice and to compare the performance of different FIT assays.Study registrationThis study is registered as PROSPERO CRD42016037723.FundingThe National Institute for Health Research Health Technology Assessment programme.

The second commonest cause of cancer death in the Western world is attributed to prostate cancer (Jensen et al, 1990). It is well documented that prostatic carcinoma shows a predilection to metastasize to the bone marrow (Jacobs, 1983). Metastatic prostate cancer remains an incurable disease and as such, is a massive clinical problem. There is clearly a need to elucidate the factors underlying the spread of prostate cancer, particularly to the skeleton.It has been suggested that the bone marrow microenvironment is conducive to the growth of prostate cancer cells, which nonselectively enter the bone marrow from the circulation (Galasko, 1981;Jacobs, 1983;Paget, 1989;Body, 1992). However, the strikingly consistent pattern of prostate metastasis within the red marrow suggests that this process may in fact be regulated (Fidler et al, 1978). The mechanism of metastasis is a complex multi-step process that is not fully understood. One critical step in this mechanism may be the attachment to and extravasation through endothelial barriers by malignant cells possibly leading to selective metastatic sites. Tumour cell binding to endothelium involves two distinct steps, an initial docking step mediated via lectin-carbohydrate interactions followed by an integrin-mediated locking step (Honn and Tang, 1992). Several endothelial and tumour adhesion molecules have been associated with metastasis. In particular the integrins β1, α2 and α5 have been shown to be expressed by prostate epithelial cells and bone marrow cells (Soligo et al, 1990;Nagle et al, 1994;Rokhlin and Cohen, 1995). The carbohydrate sialyl Lewis X has also been associated with breast and lung cancer metastasis and its ligand P selectin is found on endothelial cells (Soligo et al, 1990). Some lung, brain, liver and ovary metastatic tumour cells have been demonstrated to bind selectively to endothelial cells isolated from lung, brain, liver and ovary respectively (Nicolson and Winkelhake, 1975;Auerbach et al, 1987). These studies suggest an active regulatory role for the endothelium in metastasis (Zetter, 1990).We have shown previously that primary prostatic epithelia from both benign and malignant tissue show an accelerated growth rate within bone marrow stroma compared to control stroma (Lang et al, 1998) and also that integrin α2β1 is a major contributor to the binding of primary prostatic epithelial cells to bone marrow stroma (Lang et al, 1997). This pattern of primary prostatic epithelial cell adhesion (α2β1) is mimicked by the prostate cell line, PC3 (Kostenuik et al, 1996) and our experiments were therefore conducted with this cell line. These studies have now been extended to develop a model to investigate the interactions of prostatic epithelial cells (primary and cell lines) with the bone marrow endothelium. MATERIALS AND METHODS MaterialsGeneral chemicals were purchased from Sigma (Poole, UK). Tissue culture media and supplements were obtained from Gibco Summary Prostate cancer shows a propensity to form secondary tumours within the bone marrow. Such ...