An elemental correlation study in cancerous and normal breast tissue with successive clinical stages by neutron activation analysis

Influence of trace elements in body metabolism and their physiological importance in various diseases have motivated their accurate and quantitative determination in biological tissues and fluids. Instrumental Neutron Activation Analysis (INAA) using short and long term irradiation has been employed to determine five minor elements (Cl, K, Na, Mg, P) and 15 trace elements (As, Br, Co, Cr, Cs, Cu, Fe, Hg, Mn, Rb, Sb, Se, Sc, Sr, and Zn) in cancerous and normal breast tissue from 30 patients of four clinical stages. Several elements show enhancement in cancerous breast tissue. Selenium shows maximum enhancement of 94.7% followed by K (81.6%), Sc (66.7%), Cu (58.2%), Na (48.5%), P (44.4%), and Zn (39.2%). Some element, such as Fe, Cr, and Mn, are depressed by 30.8, 30.1, and 12.8%, respectively. These elements compete for binding sites in the cell, change its enzymatic activity and exert direct or indirect action on the carcinogenic process accelerating the growth of tumors. This is further evidenced by histopathological examination of cancerous cells showing poor cytological differentiation. An attempt has been made to correlate trace element concentrations of Se, Cu, Zn, Rb, Br, Hg, As, Co, Fe, Cr, and Mn and the ratios of Se/Zn, K/P, Cu/Zn, Na/K, and Se/Fe with the clinical stages of cancer. Inhibition of enzymatic activity caused by variation in trace element concentrations results in immunological breakdown of the body system.     

Chemometric Methods for Studying the Relationships Between Trace Elements in Laryngeal Cancer and Healthy Tissues

A quick and reliable method for the evaluation and classification of two types of tissues is presented. Several chemometric methods were applied to evaluate multivariate data of the tissue samples with respect to the content of trace elements. The content of Pb, Al, Zn, Cd, Cu, Ni and Co was determined in samples of healthy and cancerous tissue obtained from 26 patients. Determination was done at milligram/kilogram level with inductively coupled plasma optical emission spectrometry (ICP-OES) and atomic absorption spectroscopy (AAS) techniques. Contents of trace metals in studied tissues are not normally distributed; however, normal distribution was confirmed for log values. There is a statistically significant difference in the content of Zn, Cd, Cu and Al (p?<?0.01) and Ni and Co (p?<?0.05) when healthy tissue is compared to cancerous one. Correlation between contents of trace elements for studied tissues was positive; the highest was found between Zn and Cu. A chemometric methodology seems to be a promising tool for classifications of the tissue samples.     

An evaluation study of trace element content in colorectal liver metastases and surrounding normal livers by X-ray fluorescence

Background Trace elements are involved in many key pathways involving cell cycle control. The levels of trace metals such as iron, copper, and zinc in colorectal liver metastases have not previously been assessed. Methods The trace element content in snap-frozen cancerous liver tissue from patients who underwent liver resection for colorectal liver metastases was compared with the normal surrounding liver (distant from the cancer) using X-ray fluorescence (XRF). Results X-ray fluorescence was performed on a total of 60 samples from 30 patients. Of these 29 matched pairs (of cancer and normal liver distant from cancer from the same patient) were eligible for univariate analysis. Iron (0.00598 vs. 0.02306), copper (0.00541 vs. 0.00786) and zinc (0.01790 vs. 0.04873) were statistically significantly lower in the cancer tissue than the normal liver. Iron, copper, and zinc were lower in the cancer tissue than in the normal liver in 24/29 (82.8%), 23/29 (79.3%), and 28/29 (96.6%) of cases respectively. Multivariate analysis of the 60 samples revealed that zinc was the only trace element decreased in the cancer tissue after adjusting for the other elements. Zinc levels were not affected by any of the histopathological variables. Conclusion Iron, copper, and zinc are lower in colorectal liver metastases than normal liver. An investigation into the pathways underlying these differences may provide a new understanding of cancer development and possible novel therapeutic targets.     

Serum changes in trace elements during thyroid cancers

The objective was to examine changes in trace elements due to thyroid cancer in humans. Serum levels and tissue contents of trace elements (Zn, Cu, Mn, Mg, Fe and Se) were measured in 43 patients with thyroid cancer before and 4 days after surgery were compared to normal values. The serum levels of zinc in cancer patients were lower than those of normal subjects. Surgical removal of the cancer resulted in the restoration of these levels. Although serum Cu levels in patients were not different from normal, but post-operatively these levels rose significantly (p < 0.001). Levels of Fe, Mg and Mn were significantly lower (p < 0.001) post-operatively. There was no significant change in Serum Se levels. The thyroid tissue contents of these trace elements did not show a difference between the normal (Juxta-tumor) thyroid tissue and the cancerous lesion. Out of the six trace elements examined, the decrease of serum levels of zinc in cancer patients may be linked to the disease condition. It is suggested that this change: (a) may be used to demonstrate successful cancer surgery and (b) may have implications for a long-term follow-up of thyroid cancer patients.     

Inductively coupled atomic emission spectrometry and neutron activation analysis for the determination of element reference values in human lung tissue

An investigation was undertaken in order to assess the performance of neutron activation analysis and inductively coupled plasma atomic emission spectrometry techniques for determining reference values for minor and trace elements in human lungs of urban subjects. Results show that in both instances experimental conditions must be carefully optimized to guarantee reliability of experimental data. Strict criteria for tissue sampling and pretreatment also had to be set. Provisional reference values for ca. 50 elements could thus be established.

     

An elemental correlation study in cancerous breast tissue by total reflection x-ray fluorescence

The total reflection x-ray fluorescence method (TRXRF) has been employed to determine of P, S, K, Ca, Cr, Mn, Fe, Ni, Cu, Zn, Se, Rb, Sr, and Pb concentration in the benign breast tumor tissue from 68 women and in the cancerous breast tissue from 26 women. Concentrations of most of elements show enhancement in cancerous breast tissue. Examined elements compete for binding sites in the cell, change its enzymatic activity, and exert direct or indirect action on the carcinogenic process accelerating the growth of rumors. Inhibition of enzymatic activity caused by variation in trace element concentrations results in immunological breakdown of the body system. An attempt has been made to correlate measured trace element concentrations with the clinical stage of cancer. Physical bases of used analytical method, experimental setup, and the procedure of sample preparation are described.     

Serum changes in trace elements during thyroid cancers

The objective was to examine changes in trace elements due to thyroid cancer in humans. Serum levels and tissue contents of trace elements (Zn, Cu, Mn, Mg, Fe and Se) were measured in 43 patients with thyroid cancer before and 4 days after surgery were compared to normal values. The serum levels of zinc in cancer patients were lower than those of normal subjects. Surgical removal of the cancer resulted in the restoration of these levels. Although serum Cu levels in patients were not different from normal, but post-operatively these levels rose significantly (p < 0.001). Levels of Fe, Mg and Mn were significantly lower (p < 0.001) post-operatively. There was no significant change in Serum Se levels. The thyroid tissue contents of these trace elements did not show a difference between the normal (Juxta-tumor) thyroid tissue and the cancerous lesion. Out of the six trace elements examined, the decrease of serum levels of zinc in cancer patients may be linked to the disease condition. It is suggested that this change: (a) may be used to demonstrate successful cancer surgery and (b) may have implications for a long-term follow-up of thyroid cancer patients.     

Pattern recognition analysis to the variation of nasal-pharynx cancer patients' trace element levels in samples of hair,whole blood,and tissue

Pattern recognition has been used in this paper to analyze trace element levels in patients diagnosed with nasal-pharynx cancer (NPC) and in healthy control subjects. Trace elements such as Zn, Cu, Fe, Mn, and Mg have been tested in samples of hair and whole blood. Through Mahalanobis Distance Decision analysis, we have achieved good classification effects in whole blood samples: Efficiency for distinguishing patients is 96% and that of healthy controls is 90%. Classification hair samples is inferior to whole blood: Decision accuracy for patients is 58% and healthy controls is 90%. These results are also shown in a nonlinear mapping figure. At the same time, we have also determined 5 trace element levels in 16 other cancer patients' nonneoplastic and cancerous tissue, with no significant difference between them: Decision accuracy of cancerous tissue is 63%, and in nonneoplastic tissue is 50%, hence, we cannot identify them. It can be inferred that there is no idiosyncratic change of trace elements in cancer patients' neoplastic tissue, the change of a cancerous person may occur in the whole body.     

Evaluating tissue levels of the eight trace elements and heavy metals among esophagus and gastric cancer patients: A comparison between cancerous and non-cancerous tissues

BackgroundConsidering the affecting role of environmental factors including trace elements and heavy metals on the upper gastrointestinal (GI) cancers, there is paucity of empirical research in tissue evaluations.ObjectivesThe present study aimed to measure the tissue content of some trace elements and heavy metals such as zinc (Zn), chromium (Cr), manganese (Mn), tin (Sn), copper (Cu), aluminum (Al), lead (Pb), and iron (Fe) in esophagus and gastric cancerous tissues compared to the adjacent healthy tissues.MethodsIn a cross-sectional study, the aforementioned trace elements and heavy metals were evaluated among patients with esophagus and gastric cancers. During endoscopy, multiple samples were taken from cancerous lesions and the adjacent healthy tissues. The classic flame atomic absorption spectroscopy (FAAS) method was employed as the study framework.ResultsFifty patients with the mean age of 53.92 ± 8.73 were enrolled in the current study. Thirteen patients suffered from esophageal cancer and thirty-seven patients were afflicted with gastric cancer. The results revealed significant differences in the median concentrations of Zn, Cr, Sn and, Cu (P < 0.05) between the two groups. Although there were no significant changes in the tissue content in the esophageal samples, in the median concentrations of Zn, Cr and, Sn (P < 0.05) in gastric tissues, significant differences were observed. Further, the results indicated that gender enacted an affecting role in the level of some trace elements and heavy metals.ConclusionThe tissue contents of some elements were altered in gastric and esophageal cancers; this difference may reflect the underlying mechanism of cellular changing during the tumorigenesis or direct exposure of these elements. It seems that under the shade of other coexisting risk factors, larger cohort studies are suggested to be conducted to investigate other probable aspects in this area of interest.     

Trace elemental analysis of cancer-afflicted intestine by PIXE technique

Trace elemental analysis was carried out in the biological samples of cancer-afflicted intestine using the particle-induced X-ray emission technique (PIXE). A 2-MeV proton beam was employed to excite the samples. From the present results, it can be seen that the concentration of the elements Cr, Fe, and Ni are higher in the cancerous tissue of the intestine than those observed in the normal tissue, whereas the concentration levels of the element Zn is slightly lower in the cancer tissue of intestine than that observed in the normal tissue. The concentrations of S, Cl, K, Ca, Ti, Mn, Co, and Cu in the cancer tissue of the intestine are in agreement with those observed in the normal tissues within standard deviations. The present results support the previous observations that Ni and Cr are carcinogenic agents. The observed slightly low levels of zinc in the cancer tissue of the intestine suggest that zinc could possibly inhibit the tumor growth and development of neoplastic transformation. For correctly assessing the role played by the trace elements in initiating, promoting, or inhibiting cancer in various organs, there is a need for the acquisition of more data by trace elemental analysis from several investigations of this type undertaken in different regions.     

Analysis of human tissues using Energy Dispersive X Ray Fluorescence – Dark matrix determination for the application to cancer research

BackgroundX ray Fluorescence has been essayed as a suitable technique for the elemental quantification of trace element in human tissues, namely comparison of normal and cancerous tissue. However, accurate results depend on a robust quantification approach, namely correct evaluation of the samples’ dark matrix.MethodsIn order to determine the most suitable dark matrix composition for the quantification of such samples using the Fundamental Parameter approach, we have measured several Certified Reference Materials and essayed different dark matrix compositions to achieve the most accurate results. The resulting dark matrix was then applied to normal and tumor ovarian and prostate tissue samples, and the obtained results were compared with the ones obtained with a comparative method using external standard calibration curves.ResultsUsing a dark matrix composed of 10 % - H, 22 % - C, 3 % - N and 60 % - O yielded the best compromise in accuracy for the light and heavy elements. For the reduced sample size and conditions of this study, for both organs, the concentrations of transition metals decrease in tumor tissues, while the concentration of lighter elements, P and Cl, increases. On the other hand, there are elements that showed different behavior between the two types of tissue, namely Zn and S, that increase in prostate tumor tissue and decrease in ovarian tissue.ConclusionAn increase in precision was one of the improvements found with the newly developed method, as the FP-approach contemplates matrix effects and the influence of other elements in the analytes’ quantification. Additionally, the determined dark matrix can be employed in any tissue analysis application by means of EDXRF.     

Biosorptive-flotation of copper(II) from environmental water samples using sugar beet pulp as sorbent and oleic acid as surfactant

Abstract

Wounds are likely to have existed ever since mankind has existed. Wound healing is an enormously complicated process and the actual scientific mechanisms and events that take place during healing are far more complex and dynamic than might be imagined. Essential elements, especially trace elements are believed to be pivotal to the wound healing process. Their involvement in tissue regeneration and repair appears to be wide ranging and their deficiencies have been reported to impair the healing process. However, further research is required to establish the involvement of trace elements and their specific species in the wound healing process.

Thus assessments of trace element levels in wound tissues using new, reliable, verified and validated technologies could be beneficial for trace element based wound healing. Here, is an attempt made to assess the link between trace element concentrations and healing processes of chronic and acute wounds. Wound tissue samples from 58 chronic leg ulcers and 50 acute wounds were analysed for concentrations of Fe, Zn, Cu, Mn, Ca, Sn, Cr, Cd and Pb using atomic absorption spectrophotometer. Blood samples were also collected from the same patients and analysed in the same manner. All the data were tested for normality by Ryan–Joiner normality test (α = 0.05) and one-way ANOVA was done for the normally distributed data.

The results showed that the concentration of Ca, Zn, Cu and Mn were similar in both acute and chronic wounds. Apart from Ca, which showed elevated concentrations, other metal concentrations are either similar or lower than the analysed concentrations in blood. It appears that there is a significant difference in the concentrations of iron accumulated in the tissues of chronic and acute wounds.

The concentrations of Sn, Cr, Cd and Pb, which are considered as toxic metals, were not present in detectable levels with the graphite furnace atomic absorption spectrophotometry in both types of wound tissues.     

Preliminary study on the distribution of selected elements in cancerous and non-cancerous kidney tissues

In this study special interest was given to trace elements recognized as to be carcinogenic to humans. The kidney tissue sections were analyzed in order to determine the concentrations of elements present in the sample. The Synchrotron Radiation Induced X-ray Emission (SRIXE) technique was applied using a white photon microbeam. The results from cancerous parts of the kidney tissues were compared to non-cancerous parts and to the control group. In addition the iron concentration level was determined in the serum of those patients. Two-dimensional scans are presented to illustrate the differences between perfused and not-perfused tissues. According to this study there is no significant difference in the Mn concentration between cancerous and non-cancerous parts of the kidney, but the concentrations of Cd, Cr, Ti, V, Cu, Se, and Zn are at a lower concentration level in the cancerous parts than in the non-cancerous parts. A converse observation has been made for Fe. This may be associated with different metabolism and dynamics of the cancer process and both higher vascularization and need of higher blood supply in the cancerous tissue. The two-dimensional scanning of thin kidney sections showed differences in the trace element distributions depending on the analyzed samples: perfused and non-perfused. Perfusion removed blood mostly from the peritubular capillaries while in the glomerulus some capillaries had a relatively high Fe content. A low Fe concentration was observed in nephron tubules while a converse observation has been made for Cd. This may indicate that Cd is localized in the cells but not in the blood.     

Behavioral remodeling of normal and cancerous epithelial cell lines with differing invasion potential induced by substrate elastic modulus

ABSTRACT

The micro-environment of cancer cells in the body is mechanically stiffer than that of normal cells. We cultured three breast cell lines of MCF10A-normal, MCF7-noninvasive, and MDA-MB-231-invasive on PDMS substrates with different elastic moduli and different cellular features were examined.Effects of substrate stiffness on cell behavior were evident among all cell lines. Cancerous cells were more sensitive to substrate stiffness for cell behaviors related to cell motility and migration which are necessary for invasion. The invasive cancerous cells were the most motile on substrates with moderate stiffness followed by non-invasive cancerous cells. Gene markers alterations were generally according to the analyzed cell movement parameters. Results suggest that alterations in matrix stiffness may be related to cancer disease and progression.     

Fourier transform infrared microspectroscopy as a diagnostic tool for distinguishing between normal and malignant human gastric tissue

Fourier transform infrared (FTIR) microspectroscopy can be considered to be a fast and non-invasive tool for distinguishing between normal and cancerous cells and tissues without the need for laborious and invasive sampling procedures. Gastric samples from four patients (age, 65±2 years) were analysed. Samples were obtained from the organs removed during gastrectomy and then classified as normal or cancerous. Classification was based on histopathological examinations at our institution. Formalin-fixed sections of gastric tissue were analysed by FTIR- microspectroscopy. To characterize differences between sections of normal and cancerous tissue, specific regions of the spectra were analysed to study variations in the levels of metabolites. To distinguish between two conditions (normal and cancerous), changes in the relative intensity of bands in the range 600–4000 cm⁻¹ were analysed. A FTIR spectral map of the bands in the region 2800–3100 cm^–1 and 900–1800 cm^–1 were created to analyse pathological changes in tissues. The limited data available showed that normal gastric tissue had stronger absorption than cancerous tissue over a wide region in the four patients. There was a significant decrease in total biomolecular components for cancerous tissue compared with normal tissue.     

Variation in Blood and Colorectal Epithelia’s Key Trace Elements Along with Expression of Mismatch Repair Proteins from Localized and Metastatic Colorectal Cancer Patients

Colorectal cancer (CRC) is an increasingly common medical issue affecting millions worldwide, and contribution of the body’s trace elements to CRC is arguable. The concentrations and buffered status of selenium, iron, copper, zinc, and phosphorus in blood and large intestinal tissues of CRC patients are, respectively, variable and vital for cell physiology. The aim of this study was to assess selenium, iron, copper, zinc, and phosphorus variations in blood and colorectal epithelia along with examining the expression of mismatch repair proteins in CRC patients with/without metastasis for potential diagnosis/therapy. Concentrations of selenium, iron, copper, zinc, and phosphorus in blood of healthy versus CRC patients and colorectal epithelia (adenocarcinomatous versus non-adenocarcinomatous/control) were measured in 40 CRC patients (55.87 ± 11.9 years old) with/without metastasis before surgery using ICP-OES. Mismatch repair (MMR) protein expression was analyzed through histopathological/immunohistochemistry assays, which was sparse in 5 CRC patient’s colorectal tissues (12%). Compared with healthy individuals, blood and colorectal tissue’s levels of phosphorus, copper, and iron were significantly higher in the CRC patients, and more pronounced in metastatic CRC patients; conversely, blood and colorectal tissue’s selenium levels were significantly lower in metastatic patients. Unlike blood zinc, cancerous colorectal tissue’s zinc concentration was significantly lower in CRC patients compared to healthy control cohorts. There was no significant difference on the measured elements in samples from CRC patients with MMR⁻ compared to CRC patients with MMR⁺. Receiver operating characteristic analysis revealed a correlation of blood iron, zinc, copper, and phosphorus to CRC, and inappropriately low levels of blood and colorectal selenium correlated with exacerbated metastasis. Altered levels of selenium, iron, copper, zinc, and phosphorus in vivo may impact the pathogenesis and detection of CRC, and their diagnostic/therapeutic potential in CRC would be revealing.

     

Trace Elements Characteristic Based on ICP-AES and the Correlation of Flavonoids from Sparganii rhizoma

The aim of the present work was to investigate the trace elements and the correlation with flavonoids from Sparganii rhizoma. The ICP-AES and ultraviolet-visible spectroscopy were employed to analyze trace elements and flavonoids. The concentrations of trace elements and flavonoids were calculated using standard curve. The content of flavonoids was expressed as rutin equivalents. The cluster analysis was applied to evaluate geographical features of S. rhizoma from different geographical regions. The correlation analysis was used to obtain the relationship between the trace elements and flavonoids. The results indicated that the 15 trace elements were measured and the K, Ca, Mg, Na, Mn, Al, Cu, and Zn are rich in Sparganii rhizome. The different producing regions samples were classified into four groups. There was a weak relationship between trace elements and flavonoids.

     

A cellular automaton model for tumour growth in inhomogeneous environment

Most of the existing mathematical models for tumour growth and tumour-induced angiogenesis neglect blood flow. This is an important factor on which both nutrient and metabolite supply depend. In this paper we aim to address this shortcoming by developing a mathematical model which shows how blood flow and red blood cell heterogeneity influence the growth of systems of normal and cancerous cells. The model is developed in two stages. First we determine the distribution of oxygen in a native vascular network, incorporating into our model features of blood flow and vascular dynamics such as structural adaptation, complex rheology and red blood cell circulation. Once we have calculated the oxygen distribution, we then study the dynamics of a colony of normal and cancerous cells, placed in such a heterogeneous environment. During this second stage, we assume that the vascular network does not evolve and is independent of the dynamics of the surrounding tissue. The cells are considered as elements of a cellular automaton, whose evolution rules are inspired by the different behaviour of normal and cancer cells. Our aim is to show that blood flow and red blood cell heterogeneity play major roles in the development of such colonies, even when the red blood cells are flowing through the vasculature of normal, healthy tissue.     

The FEAR Before MEN: Networks of Mitotic Exit

Variations in the normal regulation of the mitotic cell cycle can lead to such global cellular changes as differential development or malignant transformation. Studies on the control of mitosis are particularly important to discover the details of the basic mechanisms responsible for normal cell division, as well as to learn about strategies employed by cancerous cells to indefinitely proliferate. The past years have brought noteworthy progress in elucidating the molecular pathways that regulate crucial events during mitosis such as: chromosome condensation, formation of the mitotic spindle, chromosome segregation, cytokinesis, and disassembly of the mitotic spindle.

Key Words:

Mitosis, FEAR, MEN     

Discovery of EST-SSRs in lung cancer: tagged ESTs with SSRs lead to differential amino acid and protein expression patterns in cancerous tissues

Tandem repeats are found in both coding and non-coding sequences of higher organisms. These sequences can be used in cancer genetics and diagnosis to unravel the genetic basis of tumor formation and progression. In this study, a possible relationship between SSR distributions and lung cancer was studied by comparative analysis of EST-SSRs in normal and lung cancerous tissues. While the EST-SSR distribution was similar between tumorous tissues, this distribution was different between normal and tumorous tissues. Trinucleotides tandem repeats were highly different; the number of trinucleotides in ESTs of lung cancer was 3 times higher than normal tissue. Significant negative correlation between normal and cancerous tissue showed that cancerous tissue generates different types of trinucleotides. GGC and CGC were the more frequent expressed trinucleotides in cancerous tissue, but these SSRs were not expressed in normal tissue. Similar to the EST level, the expression pattern of EST-SSRs-derived amino acids was significantly different between normal and cancerous tissues. Arg, Pro, Ser, Gly, and Lys were the most abundant amino acids in cancerous tissues, and Leu, Cys, Phe, and His were significantly more abundant in normal tissues than in cancerous tissues. Next, the putative functions of triplet SSR-containing genes were analyzed. In cancerous tissue, EST-SSRs produce different types of proteins. Chromodomain helicase DNA binding proteins were one of the major protein products of EST-SSRs in the cancerous library, while these proteins were not produced from EST-SSRs in normal tissue. For the first time, the findings of this study confirmed that EST-SSRs in normal lung tissues are different than in unhealthy tissues, and tagged ESTs with SSRs cause remarkable differences in amino acid and protein expression patterns in cancerous tissue. We suggest that EST-SSRs and EST-SSRs differentially expressed in cancerous tissue may be suitable candidate markers for lung cancer diagnosis and prediction.