The utility of inflammation and platelet biomarkers in patients with acute coronary syndromes.

INTRODUCTION: Thrombotic and inflammatory mechanisms are involved in the pathophysiology of acute coronary syndrome (ACS). The aim of the study was the evaluation of inflammation (white blood cells count/WBC, C-reactive protein/CRP, interleukin-6/IL-6) and platelet (platelet count/PLT, mean platelet volume/MPV, large platelet/LPLT, beta-thromboglobulin/ß-TG) biomarkers in the groups of ACS patients depending on the severity of signs and symptoms and compared to controls without coronary artery disease. MATERIALS AND METHODS: The study group included 93 patients categorized into 3 subgroups depending on the severity of signs and symptoms of ACS. PLT, MPV, LPLT, and WBC were determined on hematological analyzer, IL-6 and ß-TG were measured using the ELISA method. RESULTS: In the whole group of ACS patients WBC, CRP, IL-6, MPV, and ß-TG were significantly higher as compared to controls. Analyzing the inflammation and platelet biomarkers depending on the severity of signs and symptoms in comparison to controls, statistically significant differences for above-mentioned parameters were also found. There were no significant differences between the advancement of coronary artery changes and inflammation as well as platelet parameters, except for CRP concentrations. The AUCs for all inflammation parameters tested were similar, however the highest AUCs showed WBC and CRP. Among platelet parameters the highest AUC revealed ß-TG. CONCLUSION: Markers of inflammation and platelet activation may be associated to myocardial ischemia and myocardial injury. WBC, CRP and IL-6 as inflammation parameters and MPV and ß-TG as platelet biomarkers may be useful indicators of the presence of coronary artery disease.

CXCL9, CXCL10, CXCL11, and their receptor (CXCR3) in neuroinflammation and neurodegeneration.

The aim of this review is to present data from the available literature concerning CXCL9, CXCL10 and CXCL11, as well as their receptor 3 (CXCR3) in selected diseases of the central nervous system (CNS), such as tickborne encephalitis (TBE), neuroborreliosis (NB), Alzheimer's disease (AD), and multiple sclerosis (MS). CXCL9, CXCL10, and CXCL11 lack glutamic acid-leucine-arginine (ELR), and are unique, because they are more closely related to each other than to any other chemokine. The aforementioned chemokines are especially involved in Th1-type response and in various diseases, as their expression correlates with the tissue infiltration of T cells. Their production is strongly induced by interferon gamma (IFN-υ), the most typical Th1 cytokine. They act by binding to the CXC3 receptor. Knowledge about the action mechanism of CXCR3 and its ligands may be useful in the treatment of CNS diseases. However, data in the literature concerning the evaluation of CXCL9, CXCL10, CXCL11, and their receptor with the use of the enzyme-linked immunosorbent assay (ELISA) method is limited.

The isoform A of reticulon-4 (Nogo-A) in cerebrospinal fluid of primary brain tumor patients: influencing factors.

BACKGROUND: The influence of isoform A of reticulon-4 (Nogo-A), also known as neurite outgrowth inhibitor, on primary brain tumor development was reported. Therefore the aim was the evaluation of Nogo-A concentrations in cerebrospinal fluid (CSF) and serum of brain tumor patients compared with non-tumoral individuals. RESULTS: All serum results, except for two cases, obtained both in brain tumors and non-tumoral individuals, were below the lower limit of ELISA detection. Cerebrospinal fluid Nogo-A concentrations were significantly lower in primary brain tumor patients compared to non-tumoral individuals. The univariate linear regression analysis found that if white blood cell count increases by 1 × 103/µL, the mean cerebrospinal fluid Nogo-A concentration value decreases 1.12 times. In the model of multiple linear regression analysis predictor variables influencing cerebrospinal fluid Nogo-A concentrations included: diagnosis, sex, and sodium level. The mean cerebrospinal fluid Nogo-A concentration value was 1.9 times higher for women in comparison to men. In the astrocytic brain tumor group higher sodium level occurs with lower cerebrospinal fluid Nogo-A concentrations. We found the opposite situation in non-tumoral individuals. CONCLUSIONS: Univariate linear regression analysis revealed, that cerebrospinal fluid Nogo-A concentrations change in relation to white blood cell count. In the created model of multiple linear regression analysis we found, that within predictor variables influencing CSF Nogo-A concentrations were diagnosis, sex, and sodium level. Results may be relevant to the search for cerebrospinal fluid biomarkers and potential therapeutic targets in primary brain tumor patients. MATERIALS AND METHODS: Nogo-A concentrations were tested by means of enzyme-linked immunosorbent assay (ELISA).

CXCL9 concentrations in cerebrospinal fluid and serum of patients with tick-borne encephalitis.

INTRODUCTION: The aim of our current study was to evaluate cerebrospinal fluid (CSF) and serum CXCL9 concentrations and diagnostic usefulness of this molecule in tick-borne encephalitis (TBE). The study included TBE patients in the acute phase (TBE I) and after 2 weeks of follow-up (TBE II). The control group consisted of patients investigated for suspected central nervous system (CNS) infection, but with normal CSF findings. MATERIAL AND METHODS: Concentrations of CXCL9 were measured using enzyme-linked immunosorbent assay (ELISA). RESULTS: Cerebrospinal fluid and serum concentrations of CXCL9 in patients with TBE were significantly higher than in controls (p < 0.001). This alteration was also observed in the case of the CXCL9 index (ICXCL9; CSF CXCL9 concentration divided by serum CXCL9 concentration) (p < 0.001); moreover, ICXCL9 significantly decreased after 2 weeks (p < 0.001). This is the first study to evaluate the CSF and serum levels of CXCL9 in subjects with TBE. CONCLUSIONS: CXCL9 is a ligand for CXCR3, which was found on all Th1 memory lymphocytes present in the peripheral blood; therefore the elevated concentrations of CXCL9 in TBE patients as compared to the controls might indicate that this chemokine perhaps takes part in the trafficking of Th1 cells into the CNS. The results presented here support the hypothesis that CXCL9 may play a role in TBE. However, further studies are required to determine whether this protein might be used as a potential tool for the diagnosis and monitoring of inflammation in TBE.

[Difficulties in classifying body cavity fluids into transudate/ exudate depending on the various diagnostic criteria]. / Trudnosci w klasyfikacji plynów z jam ciala na przesiek/wysiek na podstawie róznych kryteriów diagnostycznych.

Disease processes may impair the production and reabsorption of fluid from in the body cavities, which results in its excessive accumulation. AIM: The aim of the study was the evaluation of difficulties regarding the classification of fluids from the body cavities into transudate/exudate observing the following: Light's criteria, total fluid protein concentration, and total protein ratio (TP ratio) and lactate dehydrogenase ratio (LDH ratio). MATERIALS AND METHODS: Retrospective analysis was conducted on pleural (N=314), peritoneal (N=114) and pericardial (N=10) fluids, which were tested for the total protein concentration and LDH activity both in fluid and serum and calculated on TP ratio and LDH ratio. RESULTS: Based on the total protein concentration, 278 fluids from pleural cavity were classified as an exudate; 36 as a transudate. Applying the Light's criteria 240 fluids were classified as an exudate; the remaining 74 fluids were classified as a transudate. Based on TP and LDH ratios, 229 fluids from pleural cavity were classified as an exudate; 85 as a transudate. Depending on the total protein concentration, 35 fluids from the peritoneal cavity were classified as an exudate; 79 as a transudate. Applying the Light's criteria 54 fluids were classified as an exudate; the remaining 60 fluids were classified as a transudate. Based on TP and LDH ratios, 22 fluids from peritoneal cavity were classified as an exudate; 92 as a transudate. Analysis of pericardial fluids, depending on the total protein concentration classified 9 of them as an exudate and 1 as a transudate. The same results were obtained by applying Light's criteria. Based on TP and LDH ratios, 7 fluids from pericardial cavity were classified as an exudate; 3 - as a transudate. CONCLUSIONS: Applying the Light's criteria or the total protein concentration in differential diagnostics of fluids from the body cavities resulted in qualification more of them as an exudates as compared to the analysis of the same fluids depending on the TP and LDH ratios. It can be assumed that some of the transudative/exudative fluids were incorrectly classified. Performed analysis suggest that more adequate criteria of the classification of fluids from the body cavities into transudate/exudate are of great importance.

Multiple sclerosis - etiology and diagnostic potential.

Multiple sclerosis (MS) is a chronic inflammatory and demyelinating disease of autoimmune originate. The main agents responsible for the MS development include exogenous, environmental, and genetic factors. MS is characterized by multifocal and temporally scattered central nervous system (CNS) damage which lead to the axonal damage. Among clinical courses of MS it can be distinguish relapsing-remitting multiple sclerosis (RRMS), secondary progressive multiple sclerosis (SPSM), primary progressive multiple sclerosis (PPMS), and progressive-relapsing multiple sclerosis (RPMS). Depending on the severity of signs and symptoms MS can be described as benign MS or malignant MS. MS diagnosis is based on McDonald's diagnostic criteria, which link clinical manifestation with characteristic lesions demonstrated by magnetic resonance imaging (MRI), cerebrospinal fluid (CSF) analysis, and visual evoked potentials. Among CSF laboratory tests used to the MS diagnosis are applied: Tibbling & Link IgG index, reinbegrams, and CSF isoelectrofocusing for oligoclonal bands detection. It should be emphasized, that despite huge progress regarding MS as well as the availability of different diagnostics methods this disease is still a diagnostic challenge. It may result from fact that MS has diverse clinical course and there is a lack of single test, which would be of appropriate diagnostic sensitivity and specificity for quick and accurate diagnosis.

Serum soluble CD40L concentration depending on the stage of multiple myeloma and its correlation with selected angiogenic cytokines.

INTRODUCTION    Little is known about the CD40L-CD40 pathway in hematologic malignancies, especially in multiple myeloma (MM). OBJECTIVES    The aim of the current study was to evaluate serum soluble CD40 ligand (sCD40L) concentrations in patients with newly diagnosed MM prior to treatment at different stages of disease, compared with healthy controls. To assess the clinical significance of sCD40L, we assessed correlations between the levels of sCD40L and those of angiogenic cytokines: interleukin 6 (IL-6), soluble receptor of IL-6 (sIL-6R), tumor necrosis factor α (TNF-α), soluble vascular cell adhesion molecule 1 (sVCAM-1), and platelet-derived growth factor AB (PDGF-AB), as well as with well-established biomarkers of MM activity (lactate dehydrogenase activity and percentage of bone marrow plasma cells) and with a marker of platelet activation (ß-thromboglobulin). PATIENTS AND METHODS    The study group consisted of 41 patients with newly diagnosed MM; the control group consisted of 30 healthy subjects. The level of sCD40L was determined using an enzyme-linked immunosorbent assay. RESULTS    The level of sCD40L was significantly higher in patients with MM than in controls and increased with the stage of the disease. Moreover, it significantly correlated with the levels of IL-6, sIL-6R, sVCAM-1, PDGF-AB, as well as the levels of MM activity markers and ß-thromboglobulin. CONCLUSIONS    Our findings indicate that increased serum sCD40L levels may be related to angiogenesis in patients with MM. This protein has potential clinical usefulness in MM and may be considered as an additional prognostic marker. The correlation of sCD40L with ß-thromboglobulin may indicate that in patients with MM sCD40L derives from activated platelets.

Early breast cancer screening using iron/iron oxide-based nanoplatforms with sub-femtomolar limits of detection.

Proteases, including matrix metalloproteinases (MMPs), tissue serine proteases, and cathepsins (CTS) exhibit numerous functions in tumor biology. Solid tumors are characterized by changes in protease expression levels by tumor and surrounding tissue. Therefore, monitoring protease levels in tissue samples and liquid biopsies is a vital strategy for early cancer detection. Water-dispersable Fe/Fe3O4-core/shell based nanoplatforms for protease detection are capable of detecting protease activity down to sub-femtomolar limits of detection. They feature one dye (tetrakis(carboxyphenyl)porphyrin (TCPP)) that is tethered to the central nanoparticle by means of a protease-cleavable consensus sequence and a second dye (Cy 5.5) that is directly linked. Based on the protease activities of urokinase plasminogen activator (uPA), MMPs 1, 2, 3, 7, 9, and 13, as well as CTS B and L, human breast cancer can be detected at stage I by means of a simple serum test. By monitoring CTS B and L stage 0 detection may be achieved. This initial study, comprised of 46 breast cancer patients and 20 apparently healthy human subjects, demonstrates the feasibility of protease-activity-based liquid biopsies for early cancer diagnosis.

Application of the Bead-Based Technique in Neurodegeneration: A Literature Review.

BACKGROUND: Alzheimer's disease (AD) is the most common disease causing neurodegeneration. The lower concentration of ß-amyloid 1-42 (Aß1-42) together with increased levels of total tau protein (T-tau) and phosphorylated tau protein (P-tau) in the cerebrospinal fluid (CSF) make a panel of well-established biomarkers in AD diagnosis. Addition of novel biomarkers to the gold standard biomarker panel might improve the diagnostic accuracy of neurodegeneration. This goal might be reached by the use of multiplexing, which is a simultaneous measurement of multiple analytes in a single sample volume and within a single cycle or run. OBJECTIVE/METHODS: Therefore the aim of the current review was to present, according to our best knowledge, available data concerning the evaluation of concentrations and diagnostic accuracy of well-established biomarkers in AD as well as novel biomarkers analyzed with the use of the bead-based technique. Additionally we discuss the utilization of the bead-based technique as compared to the conventional ELISA method. RESULTS: Literature data indicate that the bead-based technique revealed diagnostic sensitivity, specificity and coefficients of variation at the levels similar to ELISA. Moreover, an addition of novel biomarkers (tested by means of the bead-based technique) to the gold standard biomarker panel improved the diagnostic accuracy of neurodegeneration. CONCLUSION: Review of literature data shows that the combined analysis of classical CSF biomarkers with novel biomarkers might increase the specificity and sensitivity of performed tests. However, we concluded that the replacement of conventional ELISA with the bead-based technique requires new reference intervals for Aß1-42, T-tau and P-tau concentrations.

Does thrombopoiesis in multiple myeloma patients depend on the stage of the disease?

PURPOSE: Infiltration of the bone marrow by neoplastic plasmocytes in multiple myeloma (MM) patients might impair megakaryocytopoiesis. The aim of the study was to evaluate stage-dependent platelet count (PLT) and thrombopoietin (TPO) concentration in comparison to the control group. We also wanted to establish whether TPO might be recognized as a marker of the stage of the disease. MATERIAL/METHODS: The study group consisted of 41 patients (mean age 67.7) with newly diagnosed MM prior to treatment and categorized according to the Durie and Salmon diagnostic classification. The control group consisted of 30 healthy subjects (mean age 65.5). PLT, WBC, RBC and Hb were measured with the use of the haematological analyser. TPO was assayed with the use of ELISA and albumin with the use of the immunonephelometry method. The number of plasma cells in the bone marrow was evaluated in bone marrow smears under light microscopy. RESULTS: PLT was not statistically different as compared the control groups, but was stage-dependent. Thrombocytopenia was observed in the III stage of MM. TPO median was significantly higher in study group than in healthy subjects and it was increasing considerably with the stage of the disease. TPO concentration was negatively correlated with albumin and PLT. AUC for TPO was 0.9764. The number of plasma cells in the bone marrow was considerably increasing with the stage of the disease. CONCLUSIONS: PLT and TPO in MM patients were stage-dependent. Elevated TPO concentration in MM patients might be an unfavourable marker of the stage of the disease.

Concentrations of matrix metalloproteinases and their tissue inhibitors in the cerebrospinal fluid of patients with Alzheimer's disease.

BACKGROUND: A growing body of evidence shows the involvement of matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs) in neurodegeneration processes, but reports of their concentrations in the cerebrospinal fluid (CSF) are inconsistent. OBJECTIVE: Therefore, the aim of our study was to evaluate the CSF concentrations of MMP-2, MMP-3, MMP-9, and their inhibitors (TIMP-1 and TIMP-2) in carefully selected groups of patients with Alzheimer's disease (AD), mild cognitive impairment (MCI), and non-demented controls, whose clinical and neuropsychological diagnoses were confirmed by the corresponding CSF biomarkers of neurochemical dementia diagnostics: decreased concentrations of Aß1-42 and/or Aß42/40 ratio, and increased concentrations of Tau and pTau181 proteins. METHODS: The study included 33 AD patients, 15 subjects with MCI, and 18 elderly individuals without cognitive deficits. The CSF concentrations of MMPs and TIMPs were determined with ELISAs. RESULTS: CSF concentrations of MMP-9 were significantly lower, and the concentrations of MMP-3 significantly higher in AD patients compared to the controls. Neither MMP-2 nor TIMPs showed significant changes among the groups investigated. CONCLUSION: Altered concentrations of two out of three MMPs investigated in this study suggest that this family of biomolecules may play a role in the AD pathophysiology. Further studies are needed to establish their potential diagnostic utility.

Magnetic-Fe/Fe(3)O(4)-nanoparticle-bound SN38 as carboxylesterase-cleavable prodrug for the delivery to tumors within monocytes/macrophages.

The targeted delivery of therapeutics to the tumor site is highly desirable in cancer treatment, because it is capable of minimizing collateral damage. Herein, we report the synthesis of a nanoplatform, which is composed of a 15 ± 1 nm diameter core/shell Fe/Fe(3)O(4) magnetic nanoparticles (MNPs) and the topoisomerase I blocker SN38 bound to the surface of the MNPs via a carboxylesterase cleavable linker. This nanoplatform demonstrated high heating ability (SAR = 522 ± 40 W/g) in an AC-magnetic field. For the purpose of targeted delivery, this nanoplatform was loaded into tumor-homing double-stable RAW264.7 cells (mouse monocyte/macrophage-like cells (Mo/Ma)), which have been engineered to express intracellular carboxylesterase (InCE) upon addition of doxycycline by a Tet-On Advanced system. The nanoplatform was taken up efficiently by these tumor-homing cells. They showed low toxicity even at high nanoplatform concentration. SN38 was released successfully by switching on the Tet-On Advanced system. We have demonstrated that this nanoplatform can be potentially used for thermochemotherapy. We will be able to achieve the following goals: (1) Specifically deliver the SN38 prodrug and magnetic nanoparticles to the cancer site as the payload of tumor-homing double-stable RAW264.7 cells; (2) Release of chemotherapeutic SN38 at the cancer site by means of the self-containing Tet-On Advanced system; (3) Provide localized magnetic hyperthermia to enhance the cancer treatment, both by killing cancer cells through magnetic heating and by activating the immune system.

[Albuminuria in patients with type 2 diabetes mellitus in relation to percentage of HbA1c]. / Albuminuria u chorych na cukrzyce typu 2 w zaleznosci od odsetka HbA1c.

UNLABELLED: Albuminuria is an early marker of the microvascular and macrovascular complications in patients with type 2 diabetes mellitus. Metabolic complication accompanying the disease, especially hyperglicaemia, have significant influence on the range of albumin excretion. The aim of the study was to evaluate urinary albumin excretion and percentage of glycated hemoglobin (HbA1c), in relation to fasting and postprandial glycaemia. MATERIAL AND METHODS: Research was made in two groups of patients with confirmed albuminuria: in the 1st group with good glycemic control with HbA1c > or = 6,1%-< or = 6,5%, and in the 2-nd group with poor glycemic control with HbA1c > 6,5%-< or = 10%. The control group consisted of 21 patients with essential hypertension and coexisted albuminuria, not suffering from diabetes. The average fasting and postprandial glycemic were calculated for each patient on the basis of the last three values of glycaemia from the patient's self-control test. The extent of albuminuria and the percentage of HbA1c were determined by the immunoturbidimetric test. RESULTS: The highest albumin excretion in urine was noticed in the group with poor glycemic control, a slightly lower level of albuminuria was found in the group with good glycemic control, however the lowest level of albumin excretion was noticed in the control group. The differences were not statistically significant. The fasting glycaemia as well as postprandial glycaemia were increased in the group with higher percentage of HbA1c (p < 0,001) with comparison to the group with good glycemic control. The average percentage of HbA1c was 7,54% in the group with poor glycemic control and was significantly connected with larger glycaemia with comparison to the 2nd group with average percentage of HbA1c 6,3%. CONCLUSIONS: The excretion of albumin in urine rises with increased glycaemia and percentage of glycosylated hemoglobin. Fasting glycaemia as well as postprandial glycaemia have influence on the percentage of glycated hemoglobin.

[Assess the impact of concentrations of inflammatory markers IL-6, CRP in the presence of albuminuria in patients with type 2 diabetes]. / Ocena wplywu stezenia markerów stanu zapalnego: IL-6, CRP na wystepowanie albuminurii u chorych na cukrzyce typu 2.

UNLABELLED: Diabetic nephropathy is one of the most common complications of diabetes. Symptom of nephropathy is albuminuria, in which the mechanism of formation may participates CRP and IL-6. The aim of the study was to evaluate the concentrations of CRP and IL-6 depending on the irregularity of metabolic patients with type 2 diabetes and their impact on the occurrence of albuminuria. MATERIAL AND METHODS: The study was conducted among 68 patients with type 2 diabetes with albuminuria. Patients were divided into groups: group I - patients with type 2 diabetes with HbA1c > or = 6.1 - < or = 6.5%, group II - patients with type 2 diabetes with HbA1c > 6.5 - < or = 10.0%, K - control group, 21 patients with essential hypertension with albuminuria. The material was consisted of venal extracted for clot drawn from the basilic vain. IL 6 concentration was assessed using the ELISA method. The percentage of hemoglobin A1c (HbA1c), CRP, the extent of albuminuria was determined by immunoturbidimetric method. RESULTS: The mean urinary albumin excretion was highest in the second study group, lowerin the test group, the lowest in the control group. The average concentration of IL-6 and CRP was highest in group I, lower in group II, the lowest in the control group (p > 0.05). It has been shown a positive correlation between serum CRP and the magnitude of albuminuria in the test group of patients with type 2 diabetes with HbA1c > or = 6.1 - < or = 6.5% (p < 0.037). The relationship between serum CRP and the magnitude of albuminuria in the control group of patients with essential hypertension were at the border of statistical significance (p < 0.057). Not shown a positive correlation between these parameters in the second group of patients with type 2 diabetes with HbA1c >6.5 - < or = 10.0%. CONCLUSIONS: In patients with type 2 diabetes with better metabolic control, protein CRP is a sensitive marker of albuminuria.

Cell-delivered magnetic nanoparticles caused hyperthermia-mediated increased survival in a murine pancreatic cancer model.

Using magnetic nanoparticles to absorb alternating magnetic field energy as a method of generating localized hyperthermia has been shown to be a potential cancer treatment. This report demonstrates a system that uses tumor homing cells to actively carry iron/iron oxide nanoparticles into tumor tissue for alternating magnetic field treatment. Paramagnetic iron/ iron oxide nanoparticles were synthesized and loaded into RAW264.7 cells (mouse monocyte/ macrophage-like cells), which have been shown to be tumor homing cells. A murine model of disseminated peritoneal pancreatic cancer was then generated by intraperitoneal injection of Pan02 cells. After tumor development, monocyte/macrophage-like cells loaded with iron/ iron oxide nanoparticles were injected intraperitoneally and allowed to migrate into the tumor. Three days after injection, mice were exposed to an alternating magnetic field for 20 minutes to cause the cell-delivered nanoparticles to generate heat. This treatment regimen was repeated three times. A survival study demonstrated that this system can significantly increase survival in a murine pancreatic cancer model, with an average post-tumor insertion life expectancy increase of 31%. This system has the potential to become a useful method for specifically and actively delivering nanoparticles for local hyperthermia treatment of cancer.

Attenuation of mouse melanoma by A/C magnetic field after delivery of bi-magnetic nanoparticles by neural progenitor cells.

Localized magnetic hyperthermia as a treatment modality for cancer has generated renewed interest, particularly if it can be targeted to the tumor site. We examined whether tumor-tropic neural progenitor cells (NPCs) could be utilized as cell delivery vehicles for achieving preferential accumulation of core/shell iron/iron oxide magnetic nanoparticles (MNPs) within a mouse model of melanoma. We developed aminosiloxane-porphyrin functionalized MNPs, evaluated cell viability and loading efficiency, and transplanted neural progenitor cells loaded with this cargo into mice with melanoma. NPCs were efficiently loaded with core/shell Fe/Fe(3)O(4) MNPs with minimal cytotoxicity; the MNPs accumulated as aggregates in the cytosol. The NPCs loaded with MNPs could travel to subcutaneous melanomas, and after A/C (alternating current) magnetic field (AMF) exposure, the targeted delivery of MNPs by the cells resulted in a measurable regression of the tumors. The tumor attenuation was significant (p < 0.05) a short time (24 h) after the last of three AMF exposures.

A/C magnetic hyperthermia of melanoma mediated by iron(0)/iron oxide core/shell magnetic nanoparticles: a mouse study.

BACKGROUND: There is renewed interest in magnetic hyperthermia as a treatment modality for cancer, especially when it is combined with other more traditional therapeutic approaches, such as the co-delivery of anticancer drugs or photodynamic therapy. METHODS: The influence of bimagnetic nanoparticles (MNPs) combined with short external alternating magnetic field (AMF) exposure on the growth of subcutaneous mouse melanomas (B16-F10) was evaluated. Bimagnetic Fe/Fe3O4 core/shell nanoparticles were designed for cancer targeting after intratumoral or intravenous administration. Their inorganic center was protected against rapid biocorrosion by organic dopamine-oligoethylene glycol ligands. TCPP (4-tetracarboxyphenyl porphyrin) units were attached to the dopamine-oligoethylene glycol ligands. RESULTS: The magnetic hyperthermia results obtained after intratumoral injection indicated that micromolar concentrations of iron given within the modified core-shell Fe/Fe3O4 nanoparticles caused a significant anti-tumor effect on murine B16-F10 melanoma with three short 10-minute AMF exposures. We also observed a decrease in tumor size after intravenous administration of the MNPs followed by three consecutive days of AMF exposure 24 hrs after the MNPs injection. CONCLUSIONS: These results indicate that intratumoral administration of surface modified MNPs can attenuate mouse melanoma after AMF exposure. Moreover, we have found that after intravenous administration of micromolar concentrations, these MNPs are capable of causing an anti-tumor effect in a mouse melanoma model after only a short AMF exposure time. This is a clear improvement to state of the art.

Evaluation of PDGF-AB and sP-selectin concentrations in relation to platelet count in patients with colorectal cancer before and after surgical treatment.

INTRODUCTION: Platelet-derived growth factor (PDGF) and P-selectin, the low-molecular weight proteins located mainly in the platelet alpha-granules, are considered to be biologically active markers of platelet (PLT) activation. OBJECTIVES: The study objective was to assess levels of PDGF-AB and sP-selectin in relation to PLT blood count in patients with colorectal cancer (CRC) who were examined before and after radical surgical treatment of the cancer. PATIENTS AND METHODS: The study involved 38 CRC patients including B1 - 20 patients (T(2-3)N(1)M(0)), B2 -18 patients (T(2-3)N2M0) and 24 age and sex-matched healthy subjects (the control group). Blood samples were collected from the antecubital vein prior to and 3 months after the radical surgery. PDGF-AB and souble (s)P-selectin, the markers of PLT activation, were determined by the immunoenzymatic methods. RESULTS: In CRC patients, the levels of PDGF-AB and sP-selectin were a few times higher, whereas the PLT count was lower as compared to the control group. Moreover, these levels were statistically much higher before, compared to those after the surgery, in patients with a higher grade of clinical and histological differentiation (p <0.05) as well. However, no positive correlation was found between the PLT count and the PDGF-AB and sP-selectin levels. CONCLUSIONS: High levels of PDGF-AB and sP-selectin, the sensitive markers of PLT activation prior to surgical treatment seem to indicate cancer tissue as the source of both PDGF and sP-selectin. For this reason, PDGF-AB and sP-selectin determination may help in early non-invasive CRC evaluation in the future.

[Platelet- derived growth factor--the construction, role and it's receptors]. / Plytkopochodny czynnik wzrostu--budowa, rola i jego receptory.

CONSTRUCTION: The platelet- derived growth factor (PDGF) is a small protein which is produced by many cells. PDGF was originally identified in platelets and in serum. It is a dimeric molecule consisting of disulfide- bonded, structurally similar A- and B- polypeptide chains. There are four isoforms of PDGF: PDGF A, PDGF B, PDFG C and PDGF D. There are purified from the alpha-granules of the platelets. ROLE: PDGF is a critical regulator of mesenchymal cell migration and proliferation. It is essential for angiogenesis, embryogenesis and cancer development and progression. Clinical studies reveal that aberrant expression of PDGF and its receptors is often associated with a variety of disorders including atherosclerosis, fibroproliferative diseases of lungs and kidneys. RECEPTORS: There are two structurally related PDGF- receptors, each with its own variation in signaling mechanism. Each subunit of PDGF binds one receptor subunit, leading to receptor dimerization. The receptors are tyrosine kinases. PDGFR alpha binds all types of isoforms. PDGFR beta can bind only polypeptide B.

Nanocrystalline metal oxides as destructive adsorbents for organophosphorus compounds at ambient temperatures.

Nanocrystals of magnesium oxide react with organophosphorus compounds at room temperature by dissociative chemisorption, which we term "destructive adsorption". This process involves cleavage of P-O and P-F bonds (but not P-C bonds) and immobilization of the resultant molecular fragments. These ultrafine powders have unusual crystalline shapes and possess high surface concentrations of reactive edge/corner and defect sites, and thereby display higher surface reactivity, normalized for surface area, than typical polycrystalline material. This high surface reactivity coupled with high surface area allows their use for effective decontamination of chemical warfare agents and related toxic substances. Herein data is presented for paraoxon, diisopropylfluorophosphate (DFP), and (CH3CH2O)2P(O)CH2-SC6H5 (DEPTMP). Solid-state NMR and IR spectroscopy indicate that all OR and F groups dissociate; this leaves bound -PO4, -F, and -OR groups for paraoxon, DFP, and DEPTMP, respectively. For paraoxon, it was shown that one monolayer reacts. For DEPTMP, the OR groups dissociate, but not the P-CH2SC6H5 group. The nanocrystalline MgO reacts much faster and in higher capacity than typical activated carbon samples, which physisorb but do not destructively adsorb these phosphorous compounds.