Cancer and Calcium - Epidemiological studies of Cancer Incidence and Survival

Studies have shown that there could be an association between dietary calcium and cancer, and more specifically it has been suggested that serum calcium is involved in the etiology of cancers of the prostate. In order to explore this association we performed epidemiological studies of the association between pre-diagnostic serum calcium and prostate cancer incidence and survival. We also studied temporal trends in the survival in Hodgkin’s Lymphoma in order to evaluate the advances in treatment routines. In our relative survival analysis of Hodgkin’s Lymphoma we could see that those diagnosed in the later periods of time had considerably higher 1-, 5- and 10-year survival. This improvement in survival was especially prominent for those aged 51-65 years. Despite this, the long-term survival is still low in the older age groups. We conclude that the recent improvements in treatment strategies in Hodgkin’s Lymphoma have considerably improved survival in all ages. However, age is still an important factor indicating the need of further progress in diagnosis and treatment of older patients. The key aim of this thesis was to study whether serum calcium is involved in the etiology and prognosis of cancers of the prostate. In our studies we did not find serum calcium to be associated with incidence of prostate cancer, incidence of fatal prostate cancer, prostate cancer-specific mortality, nor relative survival in prostate cancer. We did however find a small but significant association with incidence of prostate cancer in a stratified analysis of those men who entered the cohort at a young age, and with a high body mass index. In a descriptive analysis of the variance of serum calcium in correlation with other factors, we found that serum calcium was significantly associated with age, season of screening and estrogen related factors. We conclude that though we did not find any association between prediagnostic serum calcium and prostate cancer in our study at large, our stratified analyses together with the descriptive analysis of variance makes it plausible that the association between calcium and cancer found in other studies, partly could be confounded by a mediating, if not causative factor, involving the mechanisms of calcium homeostasis, such as; sun exposure, vitamin D level, level of sex hormones, body constitution, or insulin levels. Further studies of this mechanism in general, and its association with prostate cancer risk specifically, would be of interest when further exploring the association between cancer and calcium

Progress in Hodgkin lymphoma: a population-based study on patients diagnosed in Sweden from 1973-2009.

To access publisher's full text version of this article. Please click on the hyperlink in Additional Links field.In recent decades, attention has focused on reducing long-term, treatment-related morbidity and mortality in Hodgkin lymphoma (HL). In the present study, we looked for trends in relative survival for all patients diagnosed with HL in Sweden from 1973-2009 (N = 6949; 3985 men and 2964 women; median age, 45 years) and followed up for death until the end of 2010. Patients were categorized into 6 age groups and 5 calendar periods (1973-1979, 1980-1986, 1987-1994, 1994-2000, and 2001-2009). Relative survival improved in all age groups, with the greatest improvement in patients 51-65 years of age (P < .0005). A plateau in relative survival was observed in patients below 65 years of age during the last calendar period, suggesting a reduced long-term, treatment-related mortality. The 10-year relative survival for patients diagnosed in 2000-2009 was 0.95, 0.96, 0.93, 0.80, and 0.44 for the age groups 0-18, 19-35, 36-50, 51-65, and 66-80, respectively. Therefore, despite progress, age at diagnosis remains an important prognostic factor (P < .0005). Advances in therapy for patients with limited and advanced-stage HL have contributed to an increasing cure rate. In addition, our findings support that long-term mortality of HL therapy has decreased. Elderly HL patients still do poorly, and targeted treatment options associated with fewer side effects will advance the clinical HL field.Swedish Cancer Society CAN 2009/1203 Stockholm County Council Karolinska Institutet SLL 20090201 Karolinska Institutet Foundations 2009Fobi007

Lower Blood Calcium Associates with Unfavorable Prognosis and Predicts for Bone Metastasis in NSCLC

Ionized calcium was involved in various cellular signal pathways,and regulates many cellular processes, including those relevant to tumorigenesis. We hypothesis that imbalance of calcium homeostasis is correlated with development of lung carcinomas. We collected the clinical data of 1084 patients with non small cell lung cancer (NSCLC) treated in Shandong Provincial Hospital, Shandong University. Logistic regression was used to determine the association between calcium levels and clinical characteristics, and COX regression and Kaplan-Meier model were applied to analyze risk factors on overall survival. Blood electrolytes were tested before treatment; and nearly 16% patients with NSCLC were complained with decreased blood calcium, which is more frequent than that in other electrolytes. Further, Multivariate logistic regression analysis disclosed that there were significant correlation between blood calcium decrease and moderate and poor differentiation (P = 0.012, OR = 1.926 (1.203–4.219)), squamous cell carcinoma (P = 0.024, OR = 1.968(1.094–3.540)), and bone metastasis (P = 0.032, OR = 0.396(0.235–0.669)). In multivariate COX regression analysis, advanced lymph node stage and decreased blood calcium were significantly and independent, unfavorable prognostic factors (P<0.001). Finally, the Kaplan-Meier Survival curve revealed that blood calcium decrease was associated with shorter survival (Log-rank; χ2 = 26.172,P<0.001). Our finding indicates that lower blood calcium levels are associated with a higher risk of unfavorable prognosis and bone metastasis of NSCLC

Dendrimer-Functionalized Shell-crosslinked Iron Oxide Nanoparticles for In-Vivo Magnetic Resonance Imaging of Tumors

No Abstract.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/58645/1/1671_ftp.pd

Bacteria-responsive multilayer coatings comprising polycationic nanospheres for bacteria biofilm prevention on urinary catheters

This work reports on the development of infection-preventive coatings on silicone urinary catheters that contain in their structure and release on demand antibacterial polycationic nanospheres. Polycationic aminocellulose conjugate was first sonochemically processed into nanospheres to improve its antibacterial potential compared to the bulk conjugate in solution (ACSol). Afterwards the processed aminocellulose nanospheres (ACNSs) were combined with the hyaluronic acid (HA) polyanion to build a layer-by-layer construct on silicone surfaces. Although the coating deposition was more effective when HA was coupled with ACSol than with ACNSs, the ACNSs-based coatings were thicker and displayed smoother surfaces due to the embedment of intact nanospheres. The antibacterial effect of the ACNSs multilayers was by 40 % higher compared to the ACSol coatings. This fact was further translated into more effective prevention of Pseudomonas aeruginosa biofilm formation. The coatings were stable in absence of bacteria, whereas their disassembling occurred gradually during incubation with Pseudomonas aeruginosa, and thus eradicate the biofilm upon release of antibacterial agents. Only 5 bilayers of HA/ACNSs were sufficient to prevent the biofilm formation, in contrast to the 10 bilayers of ACSol required to achieve the same effect. The antibiofilm efficiency of (HA/ACNSs)10 multilayer construct built on a Foley catheter was additionally validated under dynamic conditions using a model of catheterized bladder in which the biofilm was grown during seven days.M.M.F. acknowledges the support of the European Commissionunder the Marie Curie Intra-European Fellowship (IEF) Program (Grant Agreement ‘‘NanoQuench” FP7-331416)

Blood Magnesium, and the Interaction with Calcium, on the Risk of High-Grade Prostate Cancer

Ionized calcium (Ca) and magnesium (Mg) compete as essential messengers to regulate cell proliferation and inflammation. We hypothesized that inadequate Mg levels, perhaps relative to Ca levels (e.g. a high Ca/Mg ratio) are associated with greater prostate cancer risk.In this biomarker sub-study of the Nashville Men's Health Study (NMHS), we included 494 NMHS participants, consisting of 98 high-grade (Gleason≥7) and 100 low-grade cancer cases, 133 prostate intraepithelial neoplasia (PIN) cases, and 163 controls without cancer or PIN at biopsy. Linear and logistic regression were used to determine associations between blood Ca, Mg, and the Ca/Mg ratio across controls and case groups while adjusting for potential confounding factors.Serum Mg levels were significantly lower, while the Ca/Mg ratio was significantly higher, among high-grade cases vs. controls (p = 0.04, p = 0.01, respectively). Elevated Mg was significantly associated with a lower risk of high-grade prostate cancer (OR = 0.26 (0.09, 0.85)). An elevated Ca/Mg ratio was also associated with an increased risk of high-grade prostate cancer (OR = 2.81 (1.24, 6.36) adjusted for serum Ca and Mg). In contrast, blood Ca levels were not significantly associated with prostate cancer or PIN.Mg, Ca, or Ca/Mg levels were not associated with low-grade cancer, PIN, PSA levels, prostate volume, or BPH treatment.Low blood Mg levels and a high Ca/Mg ratio were significantly associated with high-grade prostate cancer. These findings suggest Mg affects prostate cancer risk perhaps through interacting with Ca

Multilayer Structures for Biomaterial Applications : Biomacromolecule-based Coatings

The cellular response to a biomaterial, such as a dental implant, is mainly governed by the surface properties, and can thus be altered by the introduction of a surface coating. In this thesis the buildup of a biomacromolecule-based coating formed by layerby-layer (LbL) deposition of the charged polypeptides poly(L-lysine) (PLL) and poly(L-glutamic acid) (PGA) has been studied. In an attempt to make these coatings bioactive and useful for bone-anchored implants, an amelogenin protein mixture (EMD), has been immobilized in these thin polyelectrolyte multilayer (PEM) films. Multilayers were also built by LbL deposition of the natural biomacromolecules collagen (Col) and hyaluronic acid (HA). Multilayer films of these two extra-cellular biomacromolecules should be of interest for use as a scaffold for tissue engineering. The buildup of the multilayer films has been followed in situ, using ellipsometry, quartz crystal microbalance with dissipation (QCM-D), and dual polarization interferometry (DPI). The studied PLL/PGA multilayers were found to be highly hydrated, and to exhibit a two-regime buildup behavior, with an initial “slow-growing” regime, and a second “fast-growing” regime with a linear growth in film thickness and more than linear growth in mass. A net diffusion of polypeptides into the film during the buildup led to an increase in density of the films for each layer adsorbed. A change in density was also observed in the Col/HA film, where HA penetrated and diffused into the porous fibrous Col network. The formed PLL/PGA films were further found to be rather stable during drying, and post-buildup changes in temperature and pH, not losing any mass as long as the temperature was not raised too rapidly. The film thickness responded to changes in the ambient media and collapsed reversibly when dried. A swelling/de-swelling behavior of the film was also observed for changes in the temperature and pH. The EMD protein adsorbed to silica surfaces as nanospheres, and could by itself form multilayers. The adsorption of EMD onto PLL/PGA multilayer films increased at lower pH (5.0), and EMD could be immobilized in several layers by alternate deposition of EMD and PGA.QC 2010101

Flow permeable composites of lignin and poly(vinyl alcohol) : Towards removal of bisphenol A and erythromycin from water

Monolithic composites of Polyphepan (R) or Kraft lignin embedded in a poly(vinyl alcohol) (PVA) matrix were synthesized using cryogelation technique and studied as flow permeable adsorbents for bisphenol A and erythromycin removal from water. Adsorption isotherms of bisphenol A on pristine Polyphepan provided the equilibrium dissociation constant K-L = 2.6 x 10 (6) M and the maximal binding capacity Q(max) = 20 mu mol/g; for erythromycin K-L was in the 9.6 x 10 (6) M to 5.8 x 10 (5) M range, and Q(max) was between 55 mu mol/g and 94 mu mol/g. Embedment of lignins into PVA cryogels resulted in monoliths with adequate flow permeability and the composites essentially retained the binding capacity for both bisphenol A and erythromycin. Percolation of contaminated water through the monoliths resulted in 10-fold reduction of the pollutant concentrations within 12-70 column volumes of the effluent. Due to the higher loading of lignin, the Kraft lignin-PVA composite showed higher adsorption capacity for erythromycin than Polyphepan-PVA. Stability and reversible compression of the monoliths in the flow of water were studied. Limitations are associated with leakage of soluble lignin, strongly expressed in the case of Kraft lignin-containing composites. (C) 2016 Elsevier Ltd. All rights reserved

Adsorption from saliva to silica and hydroxyapatite surfaces and elution of salivary films by SDS and delmopinol

The adsorption of human whole saliva (HWS) onto silica and hydroxyapatite surfaces (HA) was followed by quartz crystal microbalance with dissipation (QCM-D) and ellipsometry. The influence of different surface properties and adsorption media (water and PBS) on the HWS adsorption was studied. The viscoelastic properties of the saliva films formed onto the solid surfaces were estimated by the use of the Voigt-based viscoelastic film model. Furthermore, the efficiency of SDS and delmopinol to elute the adsorbed saliva film from the surfaces was investigated at different surfactant concentrations. It was observed a biphasic kinetic regime for the adsorption of saliva on the silica and HA surfaces, indicating the formation of a rigidly coupled first layer corresponding to an initial adsorption of small proteins and a more loosely bound second layer. The results further showed a higher adsorption of HWS onto the HA surfaces compared to the silica surfaces in both adsorption media (PBS and water). The adsorption in PBS led to higher adsorbed amounts on both surfaces as compared to water. SDS was found to be more efficient in removing the saliva film from both surfaces than delmopinol. The salivary film was found to be less tightly bound on to the silica surfaces since more saliva film could be removed with both SDS and delmopinol compared to from the HA surface. When saliva was adsorbed from PBS a higher energy dissipation was determined implying that a softer saliva layer is build up in PBS as opposed to in water. In the same media (water) a softer saliva layer was formed onto the HA surfaces, while in PBS the saliva layer formed at both surfaces seems to have similar structure