Monitoring the Effect of Doxorubicin Liposomal in VX2 Tumor Using Magnetic Resonance Imaging

Cancer is still one of the serious diseases threatening the lives of human beings. How to have an early diagnosis and effective treatment for tumors is a very important issue. The animal carcinoma model can provide a simulation tool for the studies of pathogenesis, biological characteristics, and therapeutic effects. Recently, drug delivery systems have been rapidly developed to effectively improve the therapeutic effects. Liposome plays an increasingly important role in clinical diagnosis and therapy for delivering a pharmaceutic or contrast agent to the targeted sites. Liposome can be absorbed and excreted by the human body, and is well known that no harm to the human body. This study aimed to compare the therapeutic effects between encapsulated (doxorubicin liposomal, Lipodox) and un-encapsulated (doxorubicin, Dox) anti-tumor drugs using magnetic resonance imaging (MRI). Twenty-four New Zealand rabbits implanted with VX2 carcinoma at left thighs were classified into three groups: control group (untreated), Dox-treated group, and LipoDox-treated group, 8 rabbits for each group. MRI scans were performed three days after tumor implantation. A 1.5T GE Signa HDxt whole body MRI scanner with a high resolution knee coil was used in this study. After a 3-plane localizer scan was performed, three-dimensional (3D) fast spin echo (FSE) T2-weighted Images (T2WI) was used for tumor volumetric quantification. Afterwards, two-dimensional (2D) spoiled gradient recalled echo (SPGR) dynamic contrast-enhanced (DCE) MRI was used for tumor perfusion evaluation. DCE-MRI was designed to acquire four baseline images, followed by contrast agent Gd-DOTA injection through the ear vein of rabbit. A series of 32 images were acquired to observe the signals change over time in the tumor and muscle. The MRI scanning was scheduled on a weekly basis for a period of four weeks to observe the tumor progression longitudinally. The Dox and LipoDox treatments were prescribed 3 times in the first week immediately after the first MRI scan; i.e. 3 days after VX2 tumor implantation. ImageJ was used to quantitate tumor volume and time course signal enhancement on DCE images. The changes of tumor size showed that the growth of VX2 tumors was effectively inhibited for both LipoDox-treated and Dox-treated groups. Furthermore, the tumor volume of LipoDox-treated group was significantly lower than that of Dox-treated group, which implies that LipoDox has better therapeutic effect than Dox. The signal intensity of LipoDox-treated group is significantly lower than that of the other two groups, which implies that targeted therapeutic drug remained in the tumor tissue. This study provides a radiation-free and non-invasive MRI method for therapeutic monitoring of targeted liposome on an animal tumor model.

Preliminary Dosimetric Evaluation of a New Therapeutic 177Lu Complex for Human Based on Biodistribution Data in Rats

Abstract—[Tris (1,10-phenanthroline) lanthanum(III)] trithiocyanate is a new compound that has shown high ability for stopping the synthesis of DNA and also acting as a photosensitizer. Nowadays, the radiation dose assessment resource (RADAR) method is known as the most common method for absorbed dose calculation. 177Lu was produced by (n, gamma) reaction in a research reactor. 177Lu-PL3 was prepared in the optimized condition. The radiochemical yield was checked by ITLC method. The biodistribution of the complex was investigated by intravenously injection to wild-type rats via their tail veins. In this study, the absorbed dose of 177Lu-PL3 to human organs was estimated by RADAR method. 177Lu was prepared with a specific activity of 2.6-3 GBq.mg-1 and radionuclide purity of 99.98 %. Final preparation of the radiolabelled complex showed high radiochemical purity of > 99%. The results show that liver and spleen have received the highest absorbed dose of 1.051 and 0.441 mSv/MBq, respectively. The absorbed dose values for these two dose-limiting tissues suggest more biological studies special in tumor-bearing animals.

Medical Image Segmentation and Detection of MR Images Based on Spatial Multiple-Kernel Fuzzy C-Means Algorithm

In this paper, a spatial multiple-kernel fuzzy C-means (SMKFCM) algorithm is introduced for segmentation problem. A linear combination of multiples kernels with spatial information is used in the kernel FCM (KFCM) and the updating rules for the linear coefficients of the composite kernels are derived as well. Fuzzy cmeans (FCM) based techniques have been widely used in medical image segmentation problem due to their simplicity and fast convergence. The proposed SMKFCM algorithm provides us a new flexible vehicle to fuse different pixel information in medical image segmentation and detection of MR images. To evaluate the robustness of the proposed segmentation algorithm in noisy environment, we add noise in medical brain tumor MR images and calculated the success rate and segmentation accuracy. From the experimental results it is clear that the proposed algorithm has better performance than those of other FCM based techniques for noisy medical MR images.

A Fuzzy Approach to Liver Tumor Segmentation with Zernike Moments

In this paper, we present a new segmentation approach for liver lesions in regions of interest within MRI (Magnetic Resonance Imaging). This approach, based on a two-cluster Fuzzy CMeans methodology, considers the parameter variable compactness to handle uncertainty. Fine boundaries are detected by a local recursive merging of ambiguous pixels with a sequential forward floating selection with Zernike moments. The method has been tested on both synthetic and real images. When applied on synthetic images, the proposed approach provides good performance, segmentations obtained are accurate, their shape is consistent with the ground truth, and the extracted information is reliable. The results obtained on MR images confirm such observations. Our approach allows, even for difficult cases of MR images, to extract a segmentation with good performance in terms of accuracy and shape, which implies that the geometry of the tumor is preserved for further clinical activities (such as automatic extraction of pharmaco-kinetics properties, lesion characterization, etc.).

Association of Overweight and Obesity with Breast Cancer

Breast cancer is in the top rate of cancer. We analyzed the prevalence of obesity and its association with breast cancer and finally we reviewed 25 article that 320 patient and 320 control which enrolled to our study. The distribution of breast cancer patients and controls with respect to their anthropometric indices in patients with higher weight, which was statistically significant (60.2 ± 10.2 kg) compared with control group (56.1 ± 11.3 kg). The body mass index of patients was (26.06+/-3.42) and significantly higher than the control group (24.1+/-1.7). Obesity leads to increased levels of adipose tissue in the body that can be stored toxins and carcinogens to produce a continuous supply. Due to the high level of fat and the role of estrogen in a woman which is endogenous estrogen of the tumor and regulates the activities of growth steroids, obesity has confirmed as a risk factor for breast cancer. Our study and other studies have shown that obesity is a risk factor for breast cancer. And it can be prevented with a weight loss intervention for breast cancer in the future.

Synthesis of PVA/γ-Fe2O3 Used in Cancer Treatment by Hyperthermia

In recent years a new method of combination treatment for cancer has been developed and studied that has led to significant advancements in the field of cancer therapy. Hyperthermia is a traditional therapy that, along with a creation of a medically approved level of heat with the help of an alternating magnetic AC current, results in the destruction of cancer cells by heat. This paper gives details regarding the production of the spherical nanocomposite PVA/γ-Fe2O3 in order to be used for medical purposes such as tumor treatment by hyperthermia. To reach a suitable and evenly distributed temperature, the nanocomposite with core-shell morphology and spherical form within a 100 to 200 nanometer size was created using phase separation emulsion, in which the magnetic nano-particles γ- Fe2O3 with an average particle size of 20 nano-meters and with different percentages of 0.2, 0.4, 0.5 and 0.6 were covered by polyvinyl alcohol. The main concern in hyperthermia and heat treatment is achieving desirable specific absorption rate (SAR) and one of the most critical factors in SAR is particle size. In this project all attempts has been done to reach minimal size and consequently maximum SAR. The morphological analysis of the spherical structure of the nanocomposite PVA/γ-Fe2O3 was achieved by SEM analyses and the study of the chemical bonds created was made possible by FTIR analysis. To investigate the manner of magnetic nanocomposite particle size distribution a DLS experiment was conducted. Moreover, to determine the magnetic behavior of the γ- Fe2O3 particle and the nanocomposite PVA/γ-Fe2O3 in different concentrations a VSM test was conducted. To sum up, creating magnetic nanocomposites with a spherical morphology that would be employed for drug loading opens doors to new approaches in developing nanocomposites that provide efficient heat and a controlled release of drug simultaneously inside the magnetic field, which are among their positive characteristics that could significantly improve the recovery process in patients.

The Toxicity of Doxorubicin with Nanotransporters

Doxorubicin (DOX) is an anthracycline drug used to treat many cancer diseases. Similarly to other cytostatic drugs, DOX has serious side effects; the biggest obstacle is the cardiotoxicity. With the aim of lowering the negative side effects and to target the DOX into the tumor tissue, the different nanoparticles (NPs) are studied. The aim of this work was to synthetized different NPs and conjugated them with DOX and determine the binding capacity of the NPs. For this experiment, carbon nanotubes (CNTs), graphene oxide (GO), fullerene (FUL) and liposomes (LIP) were used. The highest binding capacity was observed in GO (85%). Subsequently the toxicity of NPs and NPs-DOX conjugates was analyzed in in vivo system (chicken embryos). Some NPs (GO) can increase the toxicity of DOX, whereas other NPs (LIP, CNTs) decrease DOX toxicity.

The Effect of Choke on the Efficiency of Coaxial Antenna for Percutaneous Microwave Coagulation Therapy for Hepatic Tumor

There are many perceived advantages of microwave ablation have driven researchers to develop innovative antennas to effectively treat deep-seated, non-resectable hepatic tumors. In this paper a coaxial antenna with a miniaturized sleeve choke has been discussed for microwave interstitial ablation therapy, in order to reduce backward heating effects irrespective of the insertion depth into the tissue. Two dimensional Finite Element Method (FEM) is used to simulate and measure the results of miniaturized sleeve choke antenna. This paper emphasizes the importance of factors that can affect simulation accuracy, which include mesh resolution, surface heating and reflection coefficient. Quarter wavelength choke effectiveness has been discussed by comparing it with the unchoked antenna with same dimensions.

Radiobiological Model in Radiotherapy Planning for Prostate Cancer Treatment

Quantitative radiobiological models can be used to assess the optimum clinical outcome from sophisticated therapeutic modalities by calculating tumor control probability (TCP) and normal tissue complication probability (NTCP). In this study two 3D-CRT and an IMRT treatment plans were developed with an initial prescription dose of 60 Gy in 2 Gy/fraction to prostate. Sensitivity of TCP and Complication free tumor control probability (P+) to the different values of α/β ratio was investigated for various prescription doses planned to be delivered in either a fixed number of fractions (I) or in a fixed dose per fraction (II) in each of the three different treatment plans. High dose/fraction and high α/β value result in comparatively smaller P+ and IMRT plans resulted in the highest P+, mainly due to the decrease in NTCP. If α/β is lower than expected, better tumor control can be achieved by increasing dose/fraction but decreasing the number of fractions.

VHL, PBRM1 and SETD2 Genes in Kidney Cancer: A Molecular Investigation

Kidney cancer is the most lethal urological cancer accounting for 3% of adult malignancies. VHL, a tumor-suppressor gene, is best known to be associated with renal cell carcinoma (RCC). The VHL functions as negative regulator of hypoxia inducible factors. Recent sequencing efforts have identified several novel frequent mutations of histone modifying and chromatin remodeling genes in ccRCC (clear cell RCC) including PBRM1 and SETD2. The PBRM1 gene encodes the BAF180 protein, which involved in transcriptional activation and repression of selected genes. SETD2 encodes a histone methyltransferase, which may play a role in suppressing tumor development. In this study, RNAs of 30 paired tumor and normal samples that were grouped according to the types of kidney cancer and clinical characteristics of patients, including gender and average age were examined by RT-PCR, SSCP and sequencing techniques. VHL, PBRM1 and SETD2 expressions were relatively down-regulated. However, statistically no significance was found (Wilcoxon signed rank test, p>0.05). Interestingly, no mutation was observed on the contrary of previous studies. Understanding the molecular mechanisms involved in the pathogenesis of RCC has aided the development of molecular-targeted drugs for kidney cancer. Further analysis is required to identify the responsible genes rather than VHL, PBRM1 and SETD2 in kidney cancer.

Metabolites of Polygonum L. Plants Having Antitumor Properties

The article represents the results of research of antitumor activity of different structural types of plant flavonoids extracted by authors from Polygonum L. plants in commercial reserves at the territory of the Republic of Kazakhstan. For the first time ever the results comparative research of antitumor activity of plant flavonoids of different structural groups and their synthetic derivatives have been represented. The results of determination of toxicity of flavonoids in single parenteral infusion conditions have been represented. Experimental substantiation of possible mechanisms of antiproliferative and cytotoxic action of flavonoids has been suggested. The perspectives of usage of plant flavonoids as medications and creation of effective dosage forms of antitumor medicines on their basis have been substantiated.

Detecting HCC Tumor in Three Phasic CT Liver Images with Optimization of Neural Network

The aim of this work is to build a model based on tissue characterization that is able to discriminate pathological and non-pathological regions from three-phasic CT images. With our research and based on a feature selection in different phases, we are trying to design a neural network system with an optimal neuron number in a hidden layer. Our approach consists of three steps: feature selection, feature reduction, and classification. For each region of interest (ROI), 6 distinct sets of texture features are extracted such as: first order histogram parameters, absolute gradient, run-length matrix, co-occurrence matrix, autoregressive model, and wavelet, for a total of 270 texture features. When analyzing more phases, we show that the injection of liquid cause changes to the high relevant features in each region. Our results demonstrate that for detecting HCC tumor phase 3 is the best one in most of the features that we apply to the classification algorithm. The percentage of detection between pathology and healthy classes, according to our method, relates to first order histogram parameters with accuracy of 85% in phase 1, 95% in phase 2, and 95% in phase 3.

Brain Image Segmentation Using Conditional Random Field Based On Modified Artificial Bee Colony Optimization Algorithm

Tumor is an uncontrolled growth of tissues in any part of the body. Tumors are of different types and they have different characteristics and treatments. Brain tumor is inherently serious and life-threatening because of its character in the limited space of the intracranial cavity (space formed inside the skull). Locating the tumor within MR (magnetic resonance) image of brain is integral part of the treatment of brain tumor. This segmentation task requires classification of each voxel as either tumor or non-tumor, based on the description of the voxel under consideration. Many studies are going on in the medical field using Markov Random Fields (MRF) in segmentation of MR images. Even though the segmentation process is better, computing the probability and estimation of parameters is difficult. In order to overcome the aforementioned issues, Conditional Random Field (CRF) is used in this paper for segmentation, along with the modified artificial bee colony optimization and modified fuzzy possibility c-means (MFPCM) algorithm. This work is mainly focused to reduce the computational complexities, which are found in existing methods and aimed at getting higher accuracy. The efficiency of this work is evaluated using the parameters such as region non-uniformity, correlation and computation time. The experimental results are compared with the existing methods such as MRF with improved Genetic Algorithm (GA) and MRF-Artificial Bee Colony (MRF-ABC) algorithm.

Statistical Measures and Optimization Algorithms for Gene Selection in Lung and Ovarian Tumor

Microarray technology is universally used in the study of disease diagnosis using gene expression levels. The main shortcoming of gene expression data is that it includes thousands of genes and a small number of samples. Abundant methods and techniques have been proposed for tumor classification using microarray gene expression data. Feature or gene selection methods can be used to mine the genes that directly involve in the classification and to eliminate irrelevant genes. In this paper statistical measures like T-Statistics, Signal-to-Noise Ratio (SNR) and F-Statistics are used to rank the genes. The ranked genes are used for further classification. Particle Swarm Optimization (PSO) algorithm and Shuffled Frog Leaping (SFL) algorithm are used to find the significant genes from the top-m ranked genes. The Naïve Bayes Classifier (NBC) is used to classify the samples based on the significant genes. The proposed work is applied on Lung and Ovarian datasets. The experimental results show that the proposed method achieves 100% accuracy in all the three datasets and the results are compared with previous works.

Ficus deltoidea Extract Protects HaCaT Keratinocytes from UVB Irradiation-Induced Inflammation

Ficus deltoidea from the Moraceae family is a popular medicinal herb in Malaysia. It possesses strong antioxidant and antiinflammatory properties. In the present study, the anti-inflammatory effects of F. deltoidea extract on UVB-irradiated HaCaT Keratinocytes were investigated. HaCaT Keratinocytes were UVBirradiated (12.5 mJ/cm3) and were treated with 0.05, 0.08 or 0.1% of F. deltoidea extract. Cell viability following UVB irradiation was significantly higher in the groups treated with the F. deltoidea extract at doses of 0.05, 0.08 or 0.1% than in control group with UVB irradiation only. Tumor necrosis factor-α (TNF-α), interleukin-1α (IL-1α), interleukin-6 (IL-6) and cyclooxygenase (COX-2) play primary roles in the inflammation process upon UV irradiation and are known to be stimulated by UVB irradiation. Treatment with the F. deltoidea extract dramatically inhibited the UV-induced TNF-α, IL-1α, IL-6, and COX-2 expression. These results suggest that the F. deltoidea extract inhibits the production of pro-inflammatory cytokines and may be an effective protective agent for the treatment of skin diseases.

Protective Effect of Hesperidin against Cyclophosphamide Hepatotoxicity in Rats

The protective effect of hesperidin was investigated in rats exposed to liver injury induced by a single intraperitoneal injection of cyclophosphamide (CYP) at a dose of 150 mg kg-1. Hesperidin treatment (100 mg kg-1/day, orally) was applied for seven days, starting five days before CYP administration. Hesperidin significantly decreased the CYP-induced elevations of serum alanine aminotransferase, and hepatic malondialdehyde and myeloperoxidase activity, significantly prevented the depletion of hepatic glutathione peroxidase activity resulted from CYP administration. Also, hesperidin ameliorated the CYP-induced liver tissue injury observed by histopathological examination. In addition, hesperidin decreased the CYP-induced expression of inducible nitric oxide synthase, tumor necrosis factor-α, cyclooxygenase-2, Fas ligand, and caspase-9 in liver tissue. It was concluded that hesperidin may represent a potential candidate to protect against CYP-induced hepatotoxicity.

Ultra Wideband Breast Cancer Detection by Using SAR for Indication the Tumor Location

This paper presents breast cancer detection by observing the specific absorption rate (SAR) intensity for identification tumor location, the tumor is identified in coordinates (x,y,z) system. We examined the frequency between 4-8 GHz to look for the most appropriate frequency. Results are simulated in frequency 4-8 GHz, the model overview include normal breast with 50 mm radian, 5 mm diameter of tumor, and ultra wideband (UWB) bowtie antenna. The models are created and simulated in CST Microwave Studio. For this simulation, we changed antenna to 5 location around the breast, the tumor can be detected when an antenna is close to the tumor location, which the coordinate of maximum SAR is approximated the tumor location. For reliable, we experiment by random tumor location to 3 position in the same size of tumor and simulation the result again by varying the antenna position in 5 position again, and it also detectable the tumor position from the antenna that nearby tumor position by maximum value of SAR, which it can be detected the tumor with precision in all frequency between 4-8 GHz.

Performance Analysis of Brain Tumor Detection Based On Image Fusion

Medical Image fusion plays a vital role in medical field to diagnose the brain tumors which can be classified as benign or malignant. It is the process of integrating multiple images of the same scene into a single fused image to reduce uncertainty and minimizing redundancy while extracting all the useful information from the source images. Fuzzy logic is used to fuse two brain MRI images with different vision. The fused image will be more informative than the source images. The texture and wavelet features are extracted from the fused image. The multilevel Adaptive Neuro Fuzzy Classifier classifies the brain tumors based on trained and tested features. The proposed method achieved 80.48% sensitivity, 99.9% specificity and 99.69% accuracy. Experimental results obtained from fusion process prove that the use of the proposed image fusion approach shows better performance while compared with conventional fusion methodologies.

ICAM-2, A Protein of Antitumor Immune Response in Mekong Giant Catfish (Pangasianodon gigas)

ICAM-2 (intercellular adhesion molecule 2) or CD102 (Cluster of Differentiation 102) is type I transmembrane glycoproteins, composing 2-9 immunoglobulin-like C2-type domains. ICAM-2 plays the particular role in immune response and cell surveillance. It is concerned in innate and specific immunity, cell survival signal, apoptosis, and anticancer. EST clone of ICAM-2, from P. gigas blood cell EST libraries, showed high identity to human ICAM-2 (92%) with conserve region of ICAM N-terminal domain and part of Ig superfamily. Gene and protein of ICAM-2 has been founded in mammals. This is the first report of ICAM-2 in fish

Industrial Production and Clinical Application of L-Asparaginase: A Chemotherapeutic Agent

This article comprises detail information about L-asparaginase, encompassing topic such as various sources of L-asparaginase, mechanism and properties of L-asparaginase. Also describe the production, cultivation and purification of L-asparaginase along with information about the application of L-asparaginase. L-asparaginase catalyzes the conversion reaction to convert asparagine to aspartic acid and ammonia. Asparagine is a nutritional requirement for both normal and tumor cell. Present scenario has found that L-asparaginase has been found to be a best anti tumor or antileukemic agent. In the recent years this enzyme gained application in the field of clinical research pharmacologic and food industry. It has been characterized based on the enzyme assay principle hydrolyzing L-asparagine into L-aspartic acid and ammonia. It has been observed that eukaryotic microorganisms such as yeast and filamentous fungi have a potential for L-asparaginase production. L-asparaginase has been and is still one of the most lengthily studied therapeutic enzymes by scientist and researchers worldwide.