Statin use and survival in colorectal cancer: Results from a population-based cohort study and an updated systematic review and meta-analysis

BackgroundThe aim of this study was to investigate the association between statin use and survival in a population-based colorectal cancer (CRC) cohort and perform an updated meta-analysis to quantify the magnitude of any association.MethodsA cohort of 8391 patients with newly diagnosed Dukes’ A-C CRC (2009–2012) was identified from the Scottish Cancer Registry. This cohort was linked to the Prescribing Information System and the National Records of Scotland Death Records (until January 2015) to identify 1064 colorectal cancer-specific deaths. Adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) for cancer-specific mortality by statin use were calculated using time dependent Cox regression models. The systematic review included relevant studies published before January 2016. Meta-analysis techniques were used to derive combined HRs for associations between statin use and cancer-specific and overall mortality.ResultsIn the Scottish cohort, statin use before diagnosis (HR = 0.84, 95% CI 0.75–0.94), but not after (HR = 0.90, 95% CI 0.77–1.05), was associated with significantly improved cancer-specific mortality. The systematic review identified 15 relevant studies. In the meta-analysis, there was consistent (I² = 0%,heterogeneity P = 0.57) evidence of a reduction in cancer-specific mortality with statin use before diagnosis in 6 studies (n = 86,622, pooled HR = 0.82, 95% CI 0.79–0.86) but this association was less apparent and more heterogeneous (I² = 67%,heterogeneity P = 0.03) with statin use after diagnosis in 4 studies (n = 19,152, pooled HR = 0.84, 95% CI 0.68–1.04).ConclusionIn a Scottish CRC cohort and updated meta-analysis there was some evidence that statin use was associated with improved survival. However, these associations were weak in magnitude and, particularly for post-diagnosis use, varied markedly between studies.     

Diabetes,metformin use,and colorectal cancer survival in postmenopausal women

Background: Observational studies have associated metformin use with lower colorectal cancer (CRC) incidence but few studies have examined metformin's influence on CRC survival. We examined the relationships among metformin use, diabetes, and survival in postmenopausal women with CRC in the Women's Health Initiative (WHI) clinical trials and observational study. Methods: 2066 postmenopausal women with CRC were followed for a median of 4.1 years, with 589 deaths after CRC diagnosis from all causes and 414 deaths directly attributed to CRC. CRC-specific survival was compared among women with diabetes with metformin use (n = 84); women with diabetes with no metformin use (n = 128); and women without diabetes (n = 1854). Cox proportional hazard models were used to estimate associations among metformin use, diabetes and survival after CRC. Strategies to adjust for potential confounders included: multivariate adjustment with known predictors of colorectal cancer survival and construction of a propensity score for the likelihood of receiving metformin, with model stratification by propensity score quintile. Results: After adjusting for age and stage, CRC specific survival in women with diabetes with metformin use was not significantly different compared to that in women with diabetes with no metformin use (HR 0.75; 95% CI 0.40–1.38, p = 0.67) and to women without diabetes (HR 1.00; 95% CI 0.61–1.66, p = 0.99). Following propensity score adjustment, the HR for CRC-specific survival in women with diabetes with metformin use compared to non-users was 0.78 (95% CI 0.38–1.55, p = 0.47) and for overall survival was 0.86 (95% CI 0.49–1.52; p = 0.60). Conclusions: In postmenopausal women with CRC and DM, no statistically significant difference was seen in CRC specific survival in those who used metformin compared to non-users. Analyses in larger populations of colorectal cancer patients are warranted.     

Patterns of metachronous metastases after curative treatment of colorectal cancer

BackgroundThis study aimed to provide information on timing, anatomical location, and predictors for metachronous metastases of colorectal cancer based on a large consecutive series of non-selected patients.MethodsAll patients operated on with curative intent for colorectal cancer (T_anyN_anyM₀) between 2003 and 2008 in the Dutch Eindhoven Cancer Registry were included (N = 5671). By means of active follow-up by the Cancer Registry staff within ten hospitals, data on development of metastatic disease were collected. Median follow-up was 5.0 years.ResultsOf the 5671 colorectal cancer patients, 1042 (18%) were diagnosed with metachronous metastases. Most common affected sites were the liver (60%), lungs (39%), extra-regional lymph nodes (22%), and peritoneum (19%). 86% of all metastases was diagnosed within three years and the median time to diagnosis was 17 months (interquartile range 10–29 months). Male gender (HR = 1.2, 95%CI 1.03–1.32), an advanced primary T-stage (T4 vs. T3 HR = 1.6, 95%CI 1.32–1.90) and N-stage (N1 vs. N0 HR = 2.8, 95%CI 2.42–3.30 and N2 vs. N0 HR = 4.5, 95%CI 3.72–5.42), high-grade tumour differentiation (HR = 1.4, 95%CI 1.17–1.62), and a positive (HR = 2.1, 95%CI 1.68–2.71) and unknown (HR = 1.7, 95%CI 1.34–2.22) resection margin were predictors for metachronous metastases.ConclusionsDifferent patterns of metastatic spread were observed for colon and rectal cancer patients and differences in time to diagnosis were found. Knowledge on these patterns and predictors for metachronous metastases may enhance tailor-made follow-up schemes leading to earlier detection of metastasized disease and increased curative treatment options.     

Comparison of four techniques to estimate milk production in singleton-rearing non-dairy ewes

Accurate estimates of milk production or milk intake are difficult, as all methods interfere to some degree with the natural behaviour of the dam and her young, and potentially alter milk yield itself. The present study compared milk yield obtained by the “oxytocin” method, udder dimensions (UD), the isotope dilution method, and live weight change of the lamb, in an attempt to select the most accurate and convenient way of measuring milk production in non-dairy sheep. In addition, the study investigated which of the three milk-estimation techniques was an accurate predictor of growth rates of lambs. Thirty-seven singleton-bearing and rearing ewes were milked once a week, for seven consecutive weeks, using the “oxytocin” method. Prior to each afternoon milking, the external dimensions of the ewe's udder were measured. Lambs were weighed weekly for the first seven weeks of life and live weight change was calculated. The deuterium oxide (D₂O) dilution technique was used to estimate milk intake of the lambs and performed at approximately 7 days post-partum and finishing on approximately day 14. Pearson's correlation coefficients and multiple regression coefficients among techniques were calculated. The UD-models at d7 (R² = 0.35), d35 (R² = 0.36) and d42 (R² = 0.34), were the best models explaining variation in milk yield (concordance correlation coefficient (CCC) = 0.49; 0.53; 0.51; for d7, d35 and d42, respectively). The lamb live weight-change model explained the variation in milk yield best at d28 (R² = 0.32; CCC = 0.49), at d35 (R² = 0.22; CCC = 0.36) and at d42 (R² = 0.28; CCC = 0.44). At d14, the intake of milk by lambs as measured by the D₂O technique, did not explain the variation in milk yield. In conclusion, udder dimensions, lamb live weight change and lamb milk intake are relatively poor estimators of the milk yield of singleton-rearing ewes obtained by the “oxytocin” method. Additionally, udder dimensions, milk yield and lamb milk intake do not give an accurate prediction of growth rates of singleton lambs. These results emphasize that there is a difference between ewe milk production potential and lamb milk intake, which need to be considered when estimating milk production in non-dairy animals.     

The functional −94 insertion/deletion ATTG polymorphism in the promoter region of NFKB1 gene increases the risk of sporadic colorectal cancer

Objective: To investigate the allele and genotype frequencies of NFKB1 ?94 ins/del ATTG (rs28720239) polymorphism and to evaluate the association between the polymorphism and colorectal cancer (CRC) risk in Malaysian population. Methods: Genomic DNA was extracted from the peripheral blood samples of 474 study subjects, which consisted of 237 histopathologically confirmed CRC patients and an equal number of cancer-free controls. The NFKB1 ?94 ins/del ATTG (rs28720239) polymorphism was genotyped using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method and confirmed by DNA sequencing. The association between the polymorphic genotypes and CRC risk was evaluated by deriving odds ratios (ORs) and 95% confidence intervals (CIs) using unconditional logistic regression analysis. Results: The frequencies of wildtype (del/del), heterozygous (del/ins) and variant (ins/ins) genotypes in CRC patients were 31.7%, 53.6% and 14.8%, respectively, while those in cancer-free controls were 35.0%, 58.2% and 6.8%, respectively. The frequency of the variant genotype was significantly higher in cases compared to controls (P < 0.01). Evaluation of the risk association of the polymorphic genotypes revealed that the variant genotype could contribute to a significantly increased risk of CRC (OR = 2.42, 95% CI = 1.24–4.73, P < 0.01). Conclusions: The variant allele of NFKB1 ?94 ins/del ATTG (rs28362491) polymorphism is associated with higher risk of sporadic CRC in Malaysian population.     

Germline HOXB13 p.Gly84Glu mutation and risk of colorectal cancer

Introduction: The HOXB13 pGly84Glu mutation has recently been associated with an increased risk of prostate cancer but the association of other cancer sites with this allele has not been assessed. Data has suggested that HOXB13 expression levels are decreased in colorectal cancer (CRC) cell lines indicating this gene may be involved in colorectal tumourigenesis. Methods: To evaluate a potential association of this mutation with CRC, we genotyped the mutation in 2695 CRC cases and 4593 controls from population-based registries in Canada and Australia. Results: The HOXB13 pGly84Glu mutation was more common in CRC cases than controls (0.48% vs. 0.17%, P = 0.02) indicating a significant association between the HOXB13 variant and CRC risk (OR = 2.8; 95%CI: 1.2–6.8). This association was attenuated but remained significant with the inclusion of previously published and publicly available genotype data. Pedigree analysis of cases and controls revealed that 7/21 HOXB13 mutation carriers had a family history of prostate cancer. Discussion: This report is the first to suggest a risk of CRC associated with mutations in the HOXB13 gene. These findings require further validation but may be of importance in the screening and genetic counseling of families known to carry the HOXB13 pGly84Glu mutation.     

Birth weight and subsequent risk of cancer

Background: We aimed to determine the association between self-reported birth weight and incident cancer in the Women's Health Initiative Observational Study cohort, a large multiethnic cohort of postmenopausal women. Methods: 65,850 women reported their birth weight by category (<6 lbs, 6–7 lbs 15 oz, 8–9 lbs 15 oz, and ≥10 lbs). All self-reported, incident cancers were adjudicated by study staff. We used Cox proportional hazards regression to estimate crude and adjusted hazard ratios (aHR) for associations between birth weight and: (1) all cancer sites combined, (2) gynecologic cancers, and (3) several site-specific cancer sites. Results: After adjustments, birth weight was positively associated with the risk of lung cancer (p = 0.01), and colon cancer (p = 0.04). An inverse trend was observed between birth weight and risk for leukemia (p = 0.04). A significant trend was not observed with breast cancer risk (p = 0.67); however, women born weighing ≥10 lbs were less likely to develop breast cancer compared to women born between 6 lbs-7 lbs 15 oz (aHR 0.77, 95% CI 0.63, 0.94). Conclusion: Birth weight category appears to be significantly associated with the risk of any postmenopausal incident cancer, though the direction of the association varies by cancer type.     

The reliability of biomechanical variables collected during single leg squat and landing tasks

IntroductionThe aim of this study was to determine the within- and between-day reliability of lower limb biomechanical variables collected during single leg squat (SLS) and single leg landing (SLL) tasks.Methods15 recreational athletes took part in three testing sessions, two sessions on the same day and another session one week later. Kinematic and kinetic data was gathered using a ten-camera movement analysis system (Qualisys) and a force platform (AMTI) embedded into the floor.ResultsThe combined averages of within-day ICC values (ICC_SLS = 0.87; ICC_SLL = 0.90) were higher than between-days (ICC_SLS = 0.81; ICC_SLL = 0.78). Vertical GRF values (ICC_SLS = 0.90; ICC_SLL = 0.98) were more reliable than joint angles (ICC_SLS = 0.85; ICC_SLL = 0.82) and moments (ICC_SLS = 0.83; ICC_SLL = 0.87).DiscussionThis study demonstrates that all joint angles, moments, and vertical ground reaction force (GRF) variables obtained during both tasks showed good to excellent consistency with relatively low standard error of measurement values. These findings would be of relevance to practitioners who are using such measures for screening and prospective studies of rehabilitative techniques.     

The relationship between ethnicity,social deprivation and late presentation of colorectal cancer

IntroductionTumour staging at time of presentation is an important factor in determining survival in colorectal cancer. The aim of this paper is to investigate the relationship between ethnicity and deprivation in late (Stage IV) presentation of colorectal cancer.MethodsData from the Thames Cancer Registry comprising 77,057 colorectal cancer patients between the years 2000 and 2012 were analysed.ResultsA total of 17,348 patients were identified with complete data, of which 53.9% were male. Patients from a Black Afro/Caribbean background were diagnosed with CRC at a much younger age than the White British group (median age 67 compared with 72, p < 0.001). In multiple regression, ethnicity, deprivation and age were positive predictors of presenting with advanced tumour stage at time of diagnosis. Black patients were more likely to present with Stage IV tumours than white patients (OR 1.37, 95% CI 1.18–1.59, p < 0.001). Social deprivation was also a predictor of Stage IV cancer presentation, with the most deprived group (Quintile 5) 1.26 times more likely to be diagnosed with Stage IV cancer compared with the most affluent group (CI 1.13–1.40, p < 0.001). Sub-group analyses demonstrated that Black & Affluent patients were still at greater risk of Stage IV CRC than their White & Affluent counterparts (OR 1.24, 95% CI 1.11–1.45, p = 0.023). Patients with rectal cancer were less likely to present with Stage IV CRC (OR 0.66, 95% CI 0.61–0.71, p < 0.001).ConclusionRacial and age related disparities exist in tumour presentation in the United Kingdom. Patients from black and socially deprived backgrounds as well as the elderly are more likely to present with advanced tumours at time of diagnosis.     

No association between garlic intake and risk of colorectal cancer

BackgroundAlthough experimental studies suggested beneficial role of garlic intake on colorectal carcinogenesis, limited prospective cohort studies have evaluated garlic intake in relation to colorectal cancer (CRC) incidence.MethodsWe followed 76,208 women in the Nurses’ Health Study and 45,592 men in the Health Professionals Follow-up Study for up to 24 years and examined garlic intake and garlic supplement use in relation to CRC risk. Information on garlic intake and supplement use was assessed using a validated food frequency questionnaire and a Cox proportional hazard regression model was used to estimate the multivariable hazard ratio (MV-HR) and 95% confidence intervals (95% CIs).ResultsWe documented 2368 (1339 women and 1029 men) incident CRC cases and found no association between garlic intake and CRC risk; the MV-HRs (95% CIs) associated with garlic (1 clove or 4 shakes per serving) intake ≥1/day compared with <1/month were 1.21 (0.94–1.57; p-trend = 0.14) for women and 1.00 (0.71–1.42; p-trend = 0.89) for men. The MV-HRs (95% CIs) of CRC for garlic supplement use, which was used in 6% of the participants in each study, were 0.72 (0.48–1.07) for women and 1.22 (0.83–1.78) for men.ConclusionOur prospective data do not support an important role of garlic intake or garlic supplement use in colorectal carcinogenesis.     

The incidence and histo-pathological characteristics of colorectal cancer in a population based cancer registry in Zimbabwe

BackgroundData on colorectal cancer (CRC) in sub-Saharan Africa is mainly based on hospital series which suggest low incidence and frequent early onset cancers. This study characterises colorectal cancer in a population-based cancer registry in Zimbabwe.MethodsCases of CRC recorded by the Zimbabwe National Cancer Registry between 2003 and 2012 were analysed. Demographic and pathological characteristics were compared according to ethnicity and age. Trends in age standardised incidence rates (ASR) were determined.ResultsThere were 886 and 216 cases of CRC among black Africans and Caucasians respectively, and 26% of the black Africans were younger than 40 years. Signet ring cell carcinomas were more common among black Africans compared to Caucasians (4% vs 1%, p = 0.027). ASR increased by 1.9%/year and 3.9%/year among black African males and females respectively.ConclusionCRC incidence is rising among black Africans and has unique demographic and pathological characteristics.     

Measurement of DNA damage in peripheral blood by the γ-H2AX assay as predictor of colorectal cancer risk

The detection of γ-H2AX focus is one of the most sensitive ways to monitor DNA double-strand breaks (DSBs). Although changes in γ-H2AX activity have been studied in tumor cells in colorectal cancer (CRC), changes in peripheral blood lymphocytes (PBLs) have not been examined previously. We hypothesize that higher levels of irradiation-induced γ-H2AX in PBLs may be associated with an elevated risk of colorectal cancer (CRC). In a case-control study, the baseline and ionizing radiation (IR)-induced γ-H2AX levels in PBLs from frequency-matched 320 untreated CRC patients and 320 controls were detected by a laser scanning cytometer-based immunocytochemical method. We used unconditional multivariable logistic regression to evaluate CRC risk by using the ratio of IR-induced γ-H2AX to the baseline levels with adjustment of age, sex and smoking status. We found CRC cases had significantly higher γ-H2AX ratio (1.5 vs. 1.41, P < 0.0001) compared with controls. When using the median γ-H2AX ratio of controls as a cutoff point, we found higher γ-H2AX ratio was significantly associated with an increased risk of CRC (OR = 6.72, 95% CI = 4.54–9.94). Quartile analyses also showed significant dose–response relationship between higher γ-H2AX ratio and increased risk of CRC (P for trend < 0.0001). Age, sex, BMI and smoking status also influenced the association of γ-H2AX ratio with CRC risk; however, no interactions with γ-H2AX ratio were observed. These results support the premise that DSBs in peripheral blood as measured by γ-H2AX level might represent an intermediate phenotype to assess the risk of CRC. Future prospective studies are necessary to confirm our findings in independent populations.     

Correlation between VEGFR-2 receptor kinase domain-containing receptor (KDR) mRNA and angiotensin II receptor type 1 (AT1-R) mRNA in endometrial cancer

PurposeAngiogenesis, a multistep process that results in new blood vessel formation from preexisting vasculature is essential for both the growth of solid tumour and for metastasis. Stimulation of vascular endothelial growth factor receptor (VEGFR), a transmembrane glycoprotein, results in mitogenesis. Within this family of receptors, VEGFR 2/kinase-insert-domain containing receptor appears to be principally upregulated during tumorigenesis. The aim of this study was to determine the expression of VEGFR-2/kinase-insert-domain containing receptor (KDR) and its correlation with angiotensin receptor type 1 (AT1-R) and clinical factors in endometrial carcinoma.MethodsThe expression of KDR and AT1-R was studied in endometrial carcinoma and normal endometrium by Real-time RT-PCR and Western blot analysis in 136 samples. The expression profile was correlated with the clinicopathological characteristics of endometrial adenocarcinoma.ResultsWe noted a significant correlation between the expression of KDR and AT1-R in tumour grade G1, G2 and G3 (R_s = 0.50; p = 0.002, R_s = 0.69; p = 0.0001, R_s = 0.52; p = 0.005, respectively). In stage I and stage II carcinoma, a significant correlation was also found between the expression of KDR and AT1-R (R_s = 0.70, p = 0.0001, R_s = 0.67; p = 0.001, respectively). Moreover significant correlation was observed between both KDR and AT1-R in tissue with different myometrial invasion (R_s = 0.54, p = 0.0001, R_s = 0.68; p = 0.0001; respectively for tumours with invasion into the inner half and invasion into the outer half).ConclusionsBasing on received correlation between AT1-R and KDR expression and previous results we speculate that angiotensin through AT1-R modulates KDR expression and thus have influence on local VEGF level. However, further studies are required to clarify the biological interaction between KDR, AT1-R and other hormonal regulators in endometrial carcinoma.     

Valeur pronostique de la TEP/TDM dans le bilan initial du cancer du col utérin : SUVmax de la tumeur primitive et stadification ganglionnaire

PurposeWe investigated the prognostic significance of F-18 fluorodeoxyglucose (FDG) uptake measured as maximum Standardized Uptake Value (SUV_max) in primary tumor by positron emission tomography/computed tomography (PET/CT) in cervical cancer. The secondary objective was to determine the accuracy of the PET/CT for detecting pelvic lymph node (PLN) and para-aortic lymph node (PALN) metastases.MethodsThis retrospective study included 49 consecutive patients with stage IB1 to IVB cervical cancer. Univariate analysis was performed to determine the relationships between SUV_max value and pathological prognostics factors. Survival was estimated by Kaplan-Meier method. The gold standard of LN metastases was histologic.ResultsA significant difference in SUV_max was observed between stage I and stage II, stage I and stage IV and tumor size ≤ 4 cm and > 4 cm (P = 0.0001). There was a significant correlation between the SUV_max and tumor maximal size (r = 0.597) (P < 0.0001). PLN metastasis was found to be predictive of progression-free survival (P = 0.0007). The negative predictive value (NPV) of the PET/CT for PALN was 100% for locally advanced cervical carcinoma in 24 patients. The specificity and NPV of the PET/CT for PLN in eight early-stage cervical cancer were 100% and 87.5% (7/8) respectively. The PET/CT false-negative PLN measured less than 2 mm.ConclusionOur results demonstrate a correlation between SUV_max and tumor maximal size, which represents an indicator of tumor aggressiveness. PET/CT is effective to predict the absence of PALN in locally advanced cervical carcinoma. PET/CT is not sufficient to predict PLN in early-stage cancer without lymphadenectomy.     

Évaluation de la fonction ventriculaire gauche par l’utilisation d’une caméra à semi-conducteur Cadmium Zinc Telluride (CZT) : impact de l’échantillonnage temporel (8 vs 16 intervalles)

BackgroundNew CZT cameras provide an increased spatial resolution and sensitivity. The tomographic acquisition “in list mode” allows the evaluation of the left ventricular function using 8–16 intervals per cycle with an increased spatial resolution. However, the impact of temporal sampling on evaluation of the contractile function remains uncertain.Method^99mTc-sestamibi SPECT studies were acquired in 99 consecutive patients (70 men, 29 women) using an ultrafast CZT Camera (D-Spectrum, Spectrum Dynamics) and processed using both 8- and 16-interval (int). All patients underwent a stress (2 MBq/kg)-rest (6 MBq/kg) single day (stop condition: 700 KCTS within a myocardial VOI). Left ventricular function was assessed using QGS^®. Perfusion was analyzed using QPS^® and quantified using Summed Stress Score (SSS), Summed Rest Score (SRS) and Summed Difference Score (SDS) (17 segments model) and the extent of perfusion defects (% of LV).ResultsEight intervals gating overestimated the end-systolic volumes (ESV) and underestimated the left ventricular ejection fraction (LVEF) compared to 16 intervals (respectively for eight and 16 intervals: at rest [VTS: 45 ± 25 mL vs 41 ± 24 mL, P < 0.0001, LVEF: 53 ± 10% vs 59 ± 10%, P < 0.0001], and post-stress [VTS: 43 ± 24. mL vs 39 ± 24 mL, P < 0.0001; LVEF: 58 ± 10% vs 61 ± 11%, P < 0.0001]). However, it was not found significant differences between end diastolic volumes (EDV) (at rest: EDV: 98 ± 33 mL vs 97 ± 33 mL, P = NS; and post-stress: EDV: 98 ± 33 ml vs 99 ± 34 mL, P = NS). Parameters of left ventricular function were consistent between eight and 16 intervals (EDV: CCC = 0.99, ESV: CCC = 0.98, LVEF: CCC = 0.92, P < 0.0001). Correlation could not be evidenced between the extent of perfusion defect and the difference between eight and 16 intervals for the different parameters of left ventricular function both at rest and post-stress.ConclusionIn our study, comparison between eight and 16 intervals showed an overestimation of the ESV and an underestimation of LVEF, without correlation with perfusion abnormalities. The estimation of LVEF on CZT camera should take into account the chosen temporal sampling.     

Effect of pain location on spatial reorganisation of muscle activity

IntroductionWe aimed to determine whether the changes in muscle activity (in terms of both gross electromyography (EMG) and motor unit (MU) discharge characteristics) observed during pain are spatially organized with respect to pain location within a muscle which is the main contributor of the task.MethodsSurface and fine-wire EMG was recorded during matched low-force isometric plantarflexion from soleus (from four quadrants with fine-wire EMG and from the medial/lateral sides with surface EMG), both gastrocnemii heads, peroneus longus, and tibialis anterior. Four conditions were tested: two control conditions that each preceded contractions with pain induced in either the lateral (Pain_L) or medial (Pain_M) side of soleus.ResultsNeither the presence (p = 0.28) nor location (p = 0.19) of pain significantly altered gross muscle activity of any location (lateral/medial side of soleus, gastrocnemii, peroneus longus and tibialis anterior). Group data from 196 MUs show redistribution of MU activity throughout the four quadrants of soleus, irrespective of pain location. The significant decrease of MU discharge rate during pain (p < 0.0001; Pain_L: 7.3 ± 0.9–6.9 ± 1.1 Hz, Pain_M: 7.0 ± 1.1 to 6.6 ± 1.1 Hz) was similar for all quadrants of the soleus (p = 0.43), regardless of the pain location (p = 0.98). There was large inter-participant variation in respect to the characteristics of the altered MU discharge with pain.ConclusionResults from both surface and fine-wire EMG recordings do not support the hypothesis that muscle activity is reorganized in a simple systematic manner with respect to pain location.     

High expression of Rab3D predicts poor prognosis and associates with tumor progression in colorectal cancer

Rab3D belongs to Rab protein family. Previous reports showed that the expression of Rab3D was dysregulated in various types of cancer. Rab3D belongsRab3D belongs. However, little is known about the role of Rab3D in carcinogenesis and progression of colorectal cancer (CRC). Here, we first evaluated the expression of Rab3D in 32 fresh CRC and matched normal tissues and found Rab3D was dramatically increased in CRC tissues compared to normal tissues (p < 0.001). Furthermore, immunochemistry was used to investigate Rab3D expression in 300CRC tissue specimens. The expression of Rab3D significantly positively correlated with the tumor size (p = 0.041), CEA level (p = 0.007), tumor classification (p = 0.030), lymphatic metastasis (p < 0.001), distant metastasis (p = 0.013) and clinical stage (p = 0.003). We also demonstrated that overall survival is poor in CRC patients with high expression of Rab3D (p < 0.001). Finally, we showed that Rab3D activated Akt/GSK3β/Snail pathway and induced EMT process in colorectal cancer cells. In conclusion, this study establishes increased Rab3D expression is associated with invasiveness of CRC cells, and Rab3D expression status may serve as a reliable prognostic biomarker in CRC patients.     

Effects of polymorphisms in alcohol metabolism and oxidative stress genes on survival from head and neck cancer

BackgroundHeavy alcohol consumption increases risk of developing squamous cell carcinoma of the head and neck (SCCHN). Alcohol metabolism to cytotoxic and mutagenic intermediates acetaldehyde and reactive oxygen species is critical for alcohol-drinking-associated carcinogenesis. We hypothesized that polymorphisms in alcohol metabolism-related and antioxidant genes influence SCCHN survival.MethodsInterview and genotyping data (64 polymorphisms in 12 genes) were obtained from 1227 white and African-American cases from the Carolina Head and Neck Cancer Epidemiology study, a population-based case–control study of SCCHN conducted in North Carolina from 2002 to 2006. Vital status, date and cause of death through 2009 were obtained from the National Death Index. Kaplan–Meier log-rank tests and adjusted hazard ratios were calculated to identify alleles associated with survival.ResultsMost tested SNPs were not associated with survival, with the exception of the minor alleles of rs3813865 and rs8192772 in CYP2E1. These were associated with poorer cancer-specific survival (HR_rs3813865, 95%CI = 2.00, 1.33–3.01; HR_rs8192772, 95%CI = 1.62, 1.17–2.23). Hazard ratios for 8 additional SNPs in CYP2E1, GPx2, SOD1, and SOD2, though not statistically significant, were suggestive of differences in allele hazards for all-cause and/or cancer death. No consistent associations with survival were found for SNPs in ADH1B, ADH1C, ADH4, ADH7, ALDH2, GPx2, GPx4, and CAT.ConclusionsWe identified some polymorphisms in alcohol and oxidative stress metabolism genes that influence survival in subjects with SCCHN. Previously unreported associations of SNPs in CYP2E1 warrant further investigation.     

Soluble receptor for advanced glycation end products as a potential biomarker to predict weight loss and improvement of insulin sensitivity by a very low calorie diet of obese human subjects

IntroductionObesity is associated with low-grade systemic inflammation which is thought to trigger the development of comorbidities such as type 2 diabetes. The soluble receptor for advanced glycation end products (sRAGE) belongs to the innate immune system and has been linked to obesity, recently. The aim of the present study was to examine whether serum sRAGE concentrations are related to the grade of weight loss and improvement of insulin resistance due to a very low calorie diet (VLCD).Methods22 severe obese subjects (Median Body Mass Index (BMI): 44.5 kg/m²) were included in a dietary intervention study of 6 month, consisting of a very low calorie formula diet phase (VLCD: 800 kcal/d) for 12 weeks and a following 12 week weight maintenance phase. Fasting glucose, fasting insulin, adiponectin, leptin and sRAGE were determined from sera. Insulin sensitivity was estimated by Homeostasis Model Assessment (HOMA) index and leptin-to-adiponectin-ratio (LAR).ResultsMean body weight reduction by VLCD accounted to 21.7 kg with a significant improvement of insulin resistance. At baseline, sRAGE serum levels were significantly inversely related to BMI (r_S = −0.642, p = 0.001) and HOMA (r_S = −0.419, p = 0.041). Of interest, sRAGE serum levels at baseline were significantly lower in study subjects with greater reduction of BMI (p = 0.017). In addition, a significantly greater HOMA reduction was observed in subjects with lower sRAGE serum levels at baseline (p = 0.006). Finally, correlation analysis revealed, that changes of sRAGE serum levels were significantly correlated to changes of BMI (r_S = −0.650, p = 0.022) during intervention.ConclusionAnti-inflammatory sRAGE might be a potential future biomarker to predict weight loss and improvement of insulin resistance by a VLCD whereby lower baseline sRAGE serum levels indicate a better outcome of the dietary intervention.