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Showing papers in "British Journal of Cancer in 2011"


Journal ArticleDOI
TL;DR: Any future studies should be carefully designed, to prevent overestimating the effect of TILs on prognosis, and ratios between TIL subsets may be more informative.
Abstract: The prognostic influence of tumour-infiltrating lymphocytes in cancer: a systematic review with meta-analysis

1,022 citations


Journal ArticleDOI
TL;DR: The development of cold plasma tumour ablation has the potential of shifting the current paradigm of cancer treatment and enabling the transformation ofcancer treatment technologies by utilisation of another state of matter.
Abstract: Plasma is an ionised gas that is typically generated in high-temperature laboratory conditions. However, recent progress in atmospheric plasmas has led to the creation of cold plasmas with ion temperature close to room temperature. Both in-vitro and in-vivo studies revealed that cold plasmas selectively kill cancer cells. We show that: (a) cold plasma application selectively eradicates cancer cells in vitro without damaging normal cells; and (b) significantly reduces tumour size in vivo. It is shown that reactive oxygen species metabolism and oxidative stress responsive genes are deregulated. The development of cold plasma tumour ablation has the potential of shifting the current paradigm of cancer treatment and enabling the transformation of cancer treatment technologies by utilisation of another state of matter.

655 citations


Journal ArticleDOI
TL;DR: This chapter summarises the results of the preceding sections, which estimate the fraction of cancers occurring in the UK in 2010 that can be attributed to sub-optimal, past exposures of 14 lifestyle and environmental risk factors.
Abstract: This chapter summarises the results of the preceding sections, which estimate the fraction of cancers occurring in the UK in 2010 that can be attributed to sub-optimal, past exposures of 14 lifestyle and environmental risk factors. For each of 18 cancer types, we present the percentage of cases attributable to one or all of the risk factors considered (tobacco, alcohol, four elements of diet (consumption of meat, fruit and vegetables, fibre, and salt), overweight, lack of physical exercise, occupation, infections, radiation (ionising and solar), use of hormones, and reproductive history (breast feeding)).Exposure to less than optimum levels of the 14 factors was responsible for 42.7% of cancers in the UK in 2010 (45.3% in men, 40.1% in women)--a total of about 134,000 cases.Tobacco smoking is by far the most important risk factor for cancer in the UK, responsible for 60, 000 cases (19.4% of all new cancer cases) in 2010. The relative importance of other exposures differs by sex. In men, deficient intake of fruits and vegetables (6.1%), occupational exposures (4.9%) and alcohol consumption (4.6%) are next in importance, while in women, it is overweight and obesity (because of the effect on breast cancer)--responsible for 6.9% of cancers, followed by infectious agents (3.7%).Population-attributable fractions provide a valuable quantitative appraisal of the impact of different factors in cancer causation, and are thus helpful in prioritising cancer control strategies. However, quantifying the likely impact of preventive interventions requires rather complex scenario modelling, including specification of realistically achievable population distributions of risk factors, and the timescale of change, as well as the latent periods between exposure and outcome, and the rate of change following modification in exposure level.

625 citations


Journal ArticleDOI
TL;DR: In this article, the authors reported the incidence of haematological malignancy by sub-type. But they did not specify the sub-types of the malignancies.
Abstract: Incidence of haematological malignancy by sub-type: a report from the Haematological Malignancy Research Network

542 citations


Journal ArticleDOI
TL;DR: This supplement provides up-to-date estimates of the numbers (and percentages) of new cancer cases in the UK that are attributable to factors that have been established by international consensus as potentially avoidable causes of the disease.
Abstract: This supplement provides up-to-date estimates of the numbers (and percentages) of new cancer cases in the UK that are attributable to factors that have been established by international consensus as potentially avoidable causes of the disease. It therefore offers a useful guide to the relative importance of different preventive interventions.

540 citations


Journal ArticleDOI
TL;DR: NLR is highlighted as a potentially useful clinical biomarker of systemic inflammatory response in predicting clinically meaningful outcomes in two independent cohorts, and the importance of a chronic systemicinflammatory response influencing clinical outcomes in patients with mCRC is confirmed.
Abstract: Neutrophil/lymphocyte ratio predicts chemotherapy outcomes in patients with advanced colorectal cancer

421 citations


Journal ArticleDOI
TL;DR: The results of the present study indicate that the mGPS is a powerful prognostic factor when compared with other biochemical parameters and independent of tumour site in patients with cancer.
Abstract: Introduction: A selective combination of C-reactive protein and albumin (termed the modified Glasgow Prognostic Score, mGPS) has been shown to have prognostic value, independent of tumour stage, in lung, gastrointestinal and renal cancers. It is also of interest that liver function tests such as bilirubin, alkaline phosphatase and γ-glutamyl transferase, as well as serum calcium, have also been reported to predict cancer survival. The aim of the present study was to examine the relationship between an inflammation-based prognostic score (mGPS), biochemical parameters, tumour site and survival in a large cohort of patients with cancer.

416 citations


Journal ArticleDOI
TL;DR: There is an increase in incidence of PCNSL in the elderly, and elderly blacks have lower incidence compared with white population, and survival remains poor and is negatively dominated by factors associated with HIV infection and advanced age.
Abstract: Primary central nervous system lymphoma (PCNSL) is a rare subtype of extranodal non-Hodgkin lymphoma that accounts for ∼4% of newly diagnosed central nervous system (CNS) tumours. The objective of this study was to analyse the epidemiology, incidence, and outcome of these rare tumours. Primary brain and CNS lymphoma cases were identified from the Surveillance, Epidemiology, and End Results (SEER) research data sets for the years 1980–2008 for analysis of trends in incidence and survival. SEER*Stat v. 7.0.4 software was used to analyse the data. The overall incidence rate of PCNSL was 0.47 per 100 000 person-years. The incidence was significantly higher in males compared with females, blacks aged 0–49 years at diagnosis compared with whites, and whites aged 50 years and older at diagnosis compared with blacks. After a significant decline in incidence between 1995 and 1999, incidence rates rose slightly; those aged 75+ years at diagnosis had the most dramatic increase in incidence rates over time. Five-year survival rates were significantly higher in whites compared with blacks aged 0–49 years at diagnosis, but was primarily driven by white women aged 0–49 years. There is an increase in incidence of PCNSL in the elderly, and elderly blacks have lower incidence compared with white population. Survival remains poor and is negatively dominated by factors associated with HIV infection and advanced age.

400 citations


Journal ArticleDOI
TL;DR: Comparisons of two CTC detection systems based on the expression of the EpCAM antigen or on cell size highlight important discrepancies between the numbers of CTC enumerated by both techniques, especially in patients with metastatic lung carcinoma.
Abstract: BACKGROUND: Circulating tumour cells (CTCs) can provide information on patient prognosis and treatment efficacy. However, there is no universal method to detect CTC currently available. Here, we compared the performance of two CTC detection systems based on the expression of the EpCAM antigen (CellSearch assay) or on cell size (ISET assay). METHODS: Circulating tumour cells were enumerated in 60 patients with metastatic carcinomas of breast, prostate and lung origins using CellSearch according to the manufacturer’s protocol and ISET by studying cytomorphology and immunolabelling with anti-cytokeratin or lineage-specific antibodies. RESULTS: Concordant results were obtained in 55% (11 out of 20) of the patients with breast cancer, in 60% (12 out of 20) of the patients with prostate cancer and in only 20% (4 out of 20) of lung cancer patients. CONCLUSION: Our results highlight important discrepancies between the numbers of CTC enumerated by both techniques. These differences depend mostly on the tumour type. These results suggest that technologies limiting CTC capture to EpCAM-positive cells, may present important limitations, especially in patients with metastatic lung carcinoma.

368 citations


Journal ArticleDOI
TL;DR: The existence of hybrid CTCs with an epithelial/mesenchymal phenotype in patients with NSCLC is shown for the first time.
Abstract: Detection of circulating tumour cells with a hybrid (epithelial/mesenchymal) phenotype in patients with metastatic non-small cell lung cancer

357 citations


Journal ArticleDOI
TL;DR: Sex hormone concentrations were strongly associated with several established or suspected risk factors for breast cancer, and may mediate the effects of these factors on breast cancer risk.
Abstract: BACKGROUND: Breast cancer risk for postmenopausal women is positively associated with circulating concentrations of oestrogens and androgens, but the determinants of these hormones are not well understood. METHODS: Cross-sectional analyses of breast cancer risk factors and circulating hormone concentrations in more than 6000 postmenopausal women controls in 13 prospective studies. RESULTS: Concentrations of all hormones were lower in older than younger women, with the largest difference for dehydroepiandrosterone sulphate (DHEAS), whereas sex hormone-binding globulin (SHBG) was higher in the older women. Androgens were lower in women with bilateral ovariectomy than in naturally postmenopausal women, with the largest difference for free testosterone. All hormones were higher in obese than lean women, with the largest difference for free oestradiol, whereas SHBG was lower in obese women. Smokers of 15+ cigarettes per day had higher levels of all hormones than non-smokers, with the largest difference for testosterone. Drinkers of 20+ g alcohol per day had higher levels of all hormones, but lower SHBG, than non-drinkers, with the largest difference for DHEAS. Hormone concentrations were not strongly related to age at menarche, parity, age at first full-term pregnancy or family history of breast cancer. CONCLUSION: Sex hormone concentrations were strongly associated with several established or suspected risk factors for breast cancer, and may mediate the effects of these factors on breast cancer risk. British Journal of Cancer (2011) 105, 709-722. doi:10.1038/bjc.2011.254 www.bjcancer.com Published online 19 July 2011 (C) 2011 Cancer Research UK

Journal ArticleDOI
TL;DR: The delayed and sustained release of cisplatin after i.v. administration contributes to the low toxicity of NC-6004 and the recommended dose was 90 mg m−2, although DLT was not defined as per protocol.
Abstract: A Phase I clinical study of cisplatin-incorporated polymeric micelles (NC-6004) in patients with solid tumours

Journal ArticleDOI
TL;DR: Correlative studies suggest that HDAC2 expression is a predictive marker and histone hyperacetylation is a useful pharmacodynamic marker for the efficacy of this combination of vorinostat and tamoxifen, and exhibits encouraging activity in reversing hormone resistance.
Abstract: Histone deacetylases (HDACs) are crucial components of the oestrogen receptor (ER) transcriptional complex. Preclinically, HDAC inhibitors can reverse tamoxifen/aromatase inhibitor resistance in hormone receptor-positive breast cancer. This concept was examined in a phase II combination trial with correlative end points. Patients with ER-positive metastatic breast cancer progressing on endocrine therapy were treated with 400 mg of vorinostat daily for 3 of 4 weeks and 20 mg tamoxifen daily, continuously. Histone acetylation and HDAC2 expression in peripheral blood mononuclear cells were also evaluated. In all, 43 patients (median age 56 years (31–71)) were treated, 25 (58%) received prior adjuvant tamoxifen, 29 (67%) failed one prior chemotherapy regimen, 42 (98%) progressed after one, and 23 (54%) after two aromatase inhibitors. The objective response rate by Response Evaluation Criteria in Solid Tumours criteria was 19% and the clinical benefit rate (response or stable disease >24 weeks) was 40%. The median response duration was 10.3 months (confidence interval: 8.1–12.4). Histone hyperacetylation and higher baseline HDAC2 levels correlated with response. The combination of vorinostat and tamoxifen is well tolerated and exhibits encouraging activity in reversing hormone resistance. Correlative studies suggest that HDAC2 expression is a predictive marker and histone hyperacetylation is a useful pharmacodynamic marker for the efficacy of this combination.

Journal ArticleDOI
TL;DR: Presence of mutated BRAF is one of the most powerful prognostic factors for advanced and recurrent CRC, and the KRAS13 mutation showed a trend towards poor OS in patients with advanced and recurring CRC.
Abstract: Activating mutation of KRAS and BRAF are focused on as potential prognostic and predictive biomarkers in patients with colorectal cancer (CRC) treated with anti-EGFR therapies This study investigated the clinicopathological features and prognostic impact of KRAS/BRAF mutation in advanced and recurrent CRC patients Patients with advanced and recurrent CRC treated with systemic chemotherapy (n=229) were analysed for KRAS/BRAF genotypes by cycleave PCR Prognostic factors associated with survival were identified by univariate and multivariate analyses using the Cox proportional hazards model KRAS and BRAF mutations were present in 345% and 65% of patients, respectively BRAF mutated tumours were more likely to develop on the right of the colon, and to be of the poorly differentiated adenocarcinoma or mucinous carcinoma, and peritoneal metastasis The median overall survival (OS) for BRAF mutation-positive and KRAS 13 mutation-positive patients was 110 and 277 months, respectively, which was significantly worse than that for patients with wild-type (wt) KRAS and BRAF (406 months) (BRAF; HR=425, P<0001, KRAS13; HR=203, P=0024) After adjustment for significant features by multivariate Cox regression analysis, BRAF mutation was associated with poor OS (HR=423, P=0019) Presence of mutated BRAF is one of the most powerful prognostic factors for advanced and recurrent CRC The KRAS13 mutation showed a trend towards poor OS in patients with advanced and recurrent CRC

Journal ArticleDOI
TL;DR: Disulfiram/copper inhibited BCSCs and enhanced cytotoxicity of PAC in BC cell lines and may be caused by simultaneous induction of ROS and inhibition of NFκB.
Abstract: Disulfiram modulated ROS–MAPK and NF κ B pathways and targeted breast cancer cells with cancer stem cell-like properties

Journal ArticleDOI
TL;DR: It is estimated that germline mutations in the BRCA2 gene confer an ∼8.6-fold increased risk of PrCa by age 65, corresponding to an absolute risk of ∼15% by age65.
Abstract: BRCA2 is a moderate penetrance gene contributing to young-onset prostate cancer: implications for genetic testing in prostate cancer patients

Journal ArticleDOI
TL;DR: This independent validation study demonstrated similar performance indices to those recently published, however, in this study, HE4 and ROMA did not increase the detection of malignant disease compared with CA125 alone.
Abstract: HE4 and CA125 as a diagnostic test in ovarian cancer: prospective validation of the Risk of Ovarian Malignancy Algorithm

Journal ArticleDOI
TL;DR: Advice in relation to diet and cancer should include the recommendation to consume adequate amounts of fruit and vegetables, but should put most emphasis on the well-established adverse effects of obesity and high alcohol intakes.
Abstract: The possibility that fruit and vegetables may help to reduce the risk of cancer has been studied for over 30 years, but no protective effects have been firmly established. For cancers of the upper gastrointestinal tract, epidemiological studies have generally observed that people with a relatively high intake of fruit and vegetables have a moderately reduced risk, but these observations must be interpreted cautiously because of potential confounding by smoking and alcohol. For lung cancer, recent large prospective analyses with detailed adjustment for smoking have not shown a convincing association between fruit and vegetable intake and reduced risk. For other common cancers, including colorectal, breast and prostate cancer, epidemiological studies suggest little or no association between total fruit and vegetable consumption and risk. It is still possible that there are benefits to be identified: there could be benefits in populations with low average intakes of fruit and vegetables, such that those eating moderate amounts have a lower cancer risk than those eating very low amounts, and there could also be effects of particular nutrients in certain fruits and vegetables, as fruit and vegetables have very varied composition. Nutritional principles indicate that healthy diets should include at least moderate amounts of fruit and vegetables, but the available data suggest that general increases in fruit and vegetable intake would not have much effect on cancer rates, at least in well-nourished populations. Current advice in relation to diet and cancer should include the recommendation to consume adequate amounts of fruit and vegetables, but should put most emphasis on the well-established adverse effects of obesity and high alcohol intakes.

Journal ArticleDOI
TL;DR: The qHPV vaccine demonstrated high efficacy, immunogenicity, and acceptable safety in women aged 24–45 years, regardless of previous exposure to HPV vaccine type.
Abstract: Previous analyses from a randomised trial in women aged 24–45 years have shown the quadrivalent human papillomavirus (qHPV) vaccine to be efficacious in the prevention of infection, cervical intraepithelial neoplasia (CIN), and external genital lesions (EGLs) related to HPV 6/11/16/18. In this report, we present end-of-study efficacy, safety, and immunogenicity data with a median follow-up time of 4.0 years. We enrolled 3819 24–45-year-old women with no history of cervical disease or genital warts in the past 5 years. Women received quadrivalent vaccine or placebo at day 1, and at months 2 and 6. Ascertainment of CIN/EGL was accomplished through Pap testing, genital inspection, and cervicovaginal sampling (every 6 months). The main analysis was conducted in a per-protocol efficacy population (that received three doses, was naive to the relevant HPV types at day 1, and remained free of infection through month 7). Efficacy was also estimated in other naive and non-naive populations. Vaccine efficacy against the combined incidence of persistent infection, CIN/EGL related to HPV6/11/16/18 in the per-protocol population was 88.7% (95% CI: 78.1, 94.8). Efficacy for women who were seropositive and DNA negative for the relevant vaccine HPV type at the time of enrolment who received at least 1 dose was 66.9% (95% CI: 4.3, 90.6). At month 48, 91.5, 92.0, 97.4, and 47.9% of vaccinated women were seropositive to HPV 6/11/16/18, respectively. No serious vaccine-related adverse experiences were reported. The qHPV vaccine demonstrated high efficacy, immunogenicity, and acceptable safety in women aged 24–45 years, regardless of previous exposure to HPV vaccine type.

Journal ArticleDOI
TL;DR: Recent studies indicate that tumour cells with defective homologous recombination (HR) repair pathways are exquisitely sensitive to PARPi, and the identification of predictive markers for sensitivity to PARP inhibition is a priority area for research.
Abstract: Historically, PARP inhibitors (PARPi) were developed to potentiate the cytotoxic effect of certain chemotherapeutic agents and are currently being investigated in combination with chemotherapy in diverse cancer types. These agents are also radiosensitisers and clinical trials of PARPi with concurrent radiation are required. It has long been recognised that defective DNA repair pathways lead to tumour susceptibility. Recent studies indicate that tumour cells with defective homologous recombination (HR) repair pathways, the classic example being BRCA mutations, are exquisitely sensitive to PARPi. Defects in HR are not restricted to BRCA-associated tumours and other cancer types may be enriched for HR defects and hence susceptible to PARP inhibition. The identification of predictive markers for sensitivity to PARP inhibition is a priority area for research.

Journal ArticleDOI
TL;DR: Both primary tumours and liver metastases can be used for KRAS mutation analysis, and the concordance of test results between primary tumour and corresponding metastases is high.
Abstract: KRAS mutation is a negative predictive factor for treatment with anti-epidermal growth factor receptor antibody in metastatic colorectal cancer (CRC). KRAS mutation analysis is usually performed on primary tumour tissue because metastatic tissue is often not available. However, controversial data are available on the concordance of test results between primary tumours and corresponding metastases. We assessed the concordance of KRAS mutation status in a study of 305 primary colorectal tumours and their corresponding liver metastases. Patients with histologically confirmed CRC who underwent surgical resection of the primary tumour and biopsy or surgical resection of the corresponding liver metastasis were included. KRAS mutation analysis was performed for codons 12 and 13. KRAS mutation was detected in 108 out of 305 primary tumours (35.4%). In 11 cases (3.6%), we found a discordance between primary tumour and metastasis: 5 primary tumours had a KRAS mutation with a wild-type metastasis, 1 primary tumour was wild type with a KRAS mutation in the metastasis, and in 5 cases the primary tumour and the metastasis had a different KRAS mutation. We observed a high concordance of KRAS mutation status of 96.4% (95% CI 93.6–98.2%) between primary colorectal tumours and their corresponding liver metastases. In only six patients (2.0%; 95% CI 0.7–4.2%), the discordance was clinically relevant. In this largest and most homogenous study to date, we conclude that both primary tumours and liver metastases can be used for KRAS mutation analysis.

Journal ArticleDOI
TL;DR: Small-nucleolar RNAs are important in cancer prognosis, and their use as reference genes can introduce bias in associations between miRNA and pathology or outcome when determining miRNA expression.
Abstract: To investigate small-nucleolar RNAs (snoRNAs) as reference genes when measuring miRNA expression in tumour samples, given emerging evidence for their role in cancer. Four snoRNAs, commonly used for normalisation, RNU44, RNU48, RNU43 and RNU6B, and miRNA known to be associated with pathological factors, were measured by real-time polymerase chain reaction in two patient series: 219 breast cancer and 46 head and neck squamous cell carcinoma (HNSCC). SnoRNA and miRNA were then correlated with clinicopathological features and prognosis. Small-nucleolar RNA expression was as variable as miRNA expression (miR-21, miR-210, miR-10b). Normalising miRNA PCR expression data to these recommended snoRNAs introduced bias in associations between miRNA and pathology or outcome. Low snoRNA expression correlated with markers of aggressive pathology. Low levels of RNU44 were associated with a poor prognosis. RNU44 is an intronic gene in a cluster of highly conserved snoRNAs in the growth arrest specific 5 (GAS5) transcript, which is normally upregulated to arrest cell growth under stress. Low-tumour GAS5 expression was associated with a poor prognosis. RNU48 and RNU43 were also identified as intronic snoRNAs within genes that are dysregulated in cancer. Small-nucleolar RNAs are important in cancer prognosis, and their use as reference genes can introduce bias when determining miRNA expression.

Journal ArticleDOI
TL;DR: Evidence suggests that the mechanism of benefit from diet and physical activity pertains to body weight, with excess body weight being a risk factor, which is modifiable through lifestyle, and that a low-fat, high-fibre diet might be protective against cancer recurrence and progression.
Abstract: The role of diet and physical activity in breast, colorectal, and prostate cancer survivorship: a review of the literature

Journal ArticleDOI
TL;DR: Greater adherence to a Mediterranean dietary pattern could reduce overall cancer risk in this population if study subjects had a greater adherence to Mediterranean dietary patterns.
Abstract: BACKGROUND: Although several studies have investigated the association of the Mediterranean diet with overall mortality or risk of specific cancers, data on overall cancer risk are sparse. METHODS: We examined the association between adherence to Mediterranean dietary pattern and overall cancer risk using data from the European Prospective Investigation Into Cancer and nutrition, a multi-centre prospective cohort study including 142 605 men and 335 873. Adherence to Mediterranean diet was examined using a score (range: 0-9) considering the combined intake of fruits and nuts, vegetables, legumes, cereals, lipids, fish, dairy products, meat products, and alcohol. Association with cancer incidence was assessed through Cox regression modelling, controlling for potential confounders. RESULTS: In all, 9669 incident cancers in men and 21 062 in women were identified. A lower overall cancer risk was found among individuals with greater adherence to Mediterranean diet (hazard ratio = 0.96, 95% CI 0.95-0.98) for a two-point increment of the Mediterranean diet score. The apparent inverse association was stronger for smoking-related cancers than for cancers not known to be related to tobacco (P (heterogeneity) = 0.008). In all, 4.7% of cancers among men and 2.4% in women would be avoided in this population if study subjects had a greater adherence to Mediterranean dietary pattern. CONCLUSION: Greater adherence to a Mediterranean dietary pattern could reduce overall cancer risk. British Journal of Cancer (2011) 104, 1493-1499. doi:10.1038/bjc.2011.106 www.bjcancer.com Published online 5 April 2011 (C) 2011 Cancer Research UK

Journal ArticleDOI
TL;DR: The downregulation ofmiR-1 and miR-133a was a frequent event in BC, and these miRNAs were recognised as tumour suppressive and TAGLN2 may be a target of both mi RNAs and had a potential oncogenic function.
Abstract: The tumour-suppressive function of miR-1 and miR-133a targeting TAGLN2 in bladder cancer

Journal ArticleDOI
TL;DR: Detection of circulating miRNAs might provide new complementary tumour markers for ESCC by monitoring tumour dynamics through plasma miRNA assays.
Abstract: Several recent studies demonstrated that microRNAs (miRNAs) are stably detectable in plasma/serum. We hypothesised that plasma miRNAs concentrations contributed to potential biomarkers in patients with oesophageal squamous cell carcinoma (ESCC). We selected three oncogenic miRNAs (miR-21, miR-184, miR-221) and one tumour suppressive miRNA (miR-375), which are frequently reported in squamous cell carcinoma, as candidate targets for this plasma miRNA assay. This study was divided into three steps: (1) Determination of appropriate plasma miRNAs in preliminary tests. (2) Evaluation of whether the plasma miRNA assays could monitor tumour dynamics. (3) Validation study on the clinical application of plasma miRNA assays in 50 ESCC patients and 20 healthy volunteers. (1) In preliminary tests, the plasma level of miR-21 was significantly higher (P=0.0218) and that of miR-375 (P=0.0052) was significantly lower in ESCC patients than controls. (2) The high plasma miR-21 levels reflected tumour levels in all cases (100%). The plasma level of miR-21 was significantly reduced in postoperative samples (P=0.0058). (3) On validation analysis, the plasma level of miR-21 tended to be higher in ESCC patients (P=0.0649), while that of miR-375 was significantly lower (P<0.0001) and the miR-21/miR-375 ratio was significantly higher (P<0.0001) in ESCC patients than in controls. The value of the area under the receiver-operating characteristic curve (AUC) was 0.816 for the miR-21/miR-375 ratio assay. Patients with a high plasma level of miR-21 tended to have greater vascular invasion (P=0.1554) and to show a high correlation with recurrence (P=0.0164). Detection of circulating miRNAs might provide new complementary tumour markers for ESCC.

Journal ArticleDOI
TL;DR: Circulating miR-18a might provide new complementary tumour markers for pancreatic cancer as well as stably detectable in the plasma/serum.
Abstract: BACKGROUND: Several recent studies have demonstrated that microRNAs (miRNAs) are stably detectable in the plasma/serum. We hypothesised that miR-18a in the plasma is a potential biomarker in patients with pancreatic cancer. METHODS: miR-18a is located in the miR-17–92 cluster and reported to be highly expressed in pancreatic cancer tissues. This study was divided into three parts: (1) Confirmation of higher miR-18a levels in primary pancreatic cancer tissues and cell lines than in normal pancreatic tissues and a human fibroblast cell line. (2) Evaluation of the plasma miR-18a assay using quantitative RT–PCR by comparing plasma results obtained from 36 patients with pancreatic cancer and from 30 healthy volunteers. (3) Evaluation of the assay for monitoring tumour dynamics in patients with pancreatic cancer. RESULTS: (1) The expression of miR-18a was significantly higher in pancreatic cancer tissues (P ¼0.012) and pancreatic cancer cell lines (P ¼0.015) than in normal tissues and fibroblasts. (2) Plasma concentrations of miR-18a were significantly higher in pancreatic cancer patients than in controls (Po0.0001). The value of the area under the receiver-operating characteristic curve (AUC) was 0.9369. (3) Plasma levels of miR-18a were significantly lower in postoperative samples than in preoperative samples (P ¼0.0077). CONCLUSION: Circulating miR-18a might provide new complementary tumour markers for pancreatic cancer.

Journal ArticleDOI
TL;DR: D dose-limiting toxicities and maximum tolerated dose of PD 0332991, an oral cyclin-dependent kinase 4/6 inhibitor with potent anti-proliferative activity in vitro/vivo, were generally well tolerated.
Abstract: Phase I study of PD 0332991, a cyclin-dependent kinase inhibitor, administered in 3-week cycles (Schedule 2/1)

Journal ArticleDOI
TL;DR: Without new initiatives for smoking and obesity reduction, the number of cancers in the United Kingdom will increase substantially reflecting the growing and aging populations.
Abstract: Projections of cancer incidence are important for planning health services and to provide a baseline for assessing the impact of public health interventions. Rates estimated from smooth function age–period–cohort modelling of cancer incidence data from Great Britain 1975 to 2007 are extrapolated to 2030 and applied to UK population projections. Prostate and breast cancer projections take into account the effect of screening. Overall rates of cancer are projected to be stable over the next 20 years, but this masks individual changes. In both sexes, age-standardised rates of cancers of the stomach, larynx, bladder and leukaemia are projected to fall by ⩾1% per year, whereas cancers of the lip, mouth and pharynx (ICD-10 C00-C14) and melanoma are projected to increase by ⩾1% per year. The growing and aging populations will have a substantial impact: numbers of cancers in men and women are projected to increase by 55% (from 149 169 to 231 026) and 35% (from 148 716 to 200 929), respectively, between 2007 and 2030. The model used yields similar results to those of Nordpred, but is more flexible. Without new initiatives for smoking and obesity reduction, the number of cancers in the United Kingdom will increase substantially reflecting the growing and aging populations.

Journal ArticleDOI
TL;DR: Current knowledge about the roles and validated targets of miRNAs in liver cancer progression is summarised.
Abstract: Primary liver cancer, predominantly consisting of hepatocellular carcinoma (HCC), is one of the most common and aggressive human malignancies worldwide. MicroRNAs (miRNAs) are a class of small non-coding RNAs that regulate gene expression post-transcriptionally. Emerging evidence indicates that miRNAs are often deregulated in HCC, and that some specific miRNAs are associated with the clinicopathological features of HCC. Recent work demonstrates that miRNAs have essential roles in HCC progression and directly contribute to cell proliferation, avoidance of apoptotic cell death, and metastasis of HCC by targeting a large number of critical protein-coding genes. The discovery of the aberrantly expressed miRNAs and their corresponding targets has opened a novel avenue to investigate the molecular mechanism of HCC progression and to develop potential therapeutics against HCC. In this review, we summarise current knowledge about the roles and validated targets of miRNAs in liver cancer progression.