Search results for: tumor evolution

Authors: Thieu-Thi Tra My

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Undifferentiated embryonal sarcoma of the liver (UESL), a rare malignant mesenchymal tumor, is commonly seen in children. The symptoms and imaging were not specific, so it could be mimicked with other tumors or liver abscesses. The tumor often appears as a large heterogeneous echoic solid mass with small cystic areas while showing a cyst-like appearance on CT and MRI. The histopathological manifestation of the UESL consisted of stellate-shaped and spindle cells scattered on a myxoid background with high mitotic count. Cells with multiple or bizarre nuclear were also observed. Here, we aimed to describe a 9-year-old male diagnosed with UESL focused on imaging and histopathological characteristics.

Keywords: undifferentiated embryonal sarcoma of liver, UESL, liver sarcoma, liver tumor, children

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Authors: Muhammad Hassan Khalil, Xu Jiadong

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Early detection through screening is the best tool short of a perfect treatment against the malignant tumor inside the breast of a woman. By detecting cancer in its early stages, it can be recognized and treated before it has the opportunity to spread and change into potentially dangerous. Microwave tomography is a new imaging method based on contrast in dielectric properties of materials. The mathematical theory of microwave tomography involves solving an inverse problem for Maxwell’s equations. In this paper, we present designed antenna for breast cancer detection, which will use in microwave tomography configuration.

Keywords: microwave imaging, inverse scattering, breast cancer, malignant tumor detection

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Authors: Daniela Proca, Yuan Rong, Salvatore Luceno, Jalil Nasibli

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Introduction: Solitary Fibrous Tumors (SFT) have many histologic mimickers and the only way to diagnose it, particularly in an unusual location, such as peripheral nerve trunks, is to use a comprehensive immunohistochemical staining panel. Monoclonal STAT6 immunostain is highly sensitive and specific for SFTs and particularly useful in the diagnosis of difficult SFT cases. Methods: We describe a solitary fibrous tumor (SFT) involving the right branchial plexus in a 66 yo female with 4-year history of slowly growing chest wall mass with recent dysesthesias in fingers 4th and 5th. MRI showed a well-circumscribed heterogenous mass measuring 5.4 x 3.8 x 4.0 cm and encircling peripheral nerves of the branchial plexus; no involvement of the bone or muscle was noted. A biopsy showed a bland spindled and epithelioid proliferation with no significant mitotic activity, no necrosis, and no atypia; peripheral nerve fascicles were encircled by the lesion. The main clinical and pathologic differential diagnosis included peripheral nerve sheath tumor, particularly schwannoma; HE microscopy didn’t show the classic Antoni A and B areas but showed focal subtle nuclear palisading, as well as prominent vessels with hyalinization. Immunohistochemical stains showed focal, weak cytoplasmic S100 positivity in the lesion; CD 34 and Vimentin were strongly and diffusely positive; the neoplastic cells were negative with AE1/AE3, EMA, CD31, SMA, Desmin, Calretinin, HMB-45, Melan A, PAX-8, NSE. The immunohistochemical and histologic pattern was not typical of peripheral nerve sheath tumor. On additional stains, the tumor was positive with STAT-6 and bcl-2 and focally positive with CD99. Given this profile, the final diagnosis was that of a solitary fibrous tumor. Results: NA Conclusion: Very few SFTs involving peripheral nerves and mimicking a peripheral nerve sheath tumor are described in the literature. Although histologically benign on this biopsy, long-term follow-up is required because of the risk of recurrence of these tumors and their uncertain biological behavior.

Keywords: solitary fibrous tumor, pathology, diagnosis, immunohistochemistry

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Authors: Madhu Gupta, G. P. Agrawa, Suresh P. Vyas

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Certain tumor cells overexpress a membrane-spanning molecule aminopeptidase N (CD13) isoform, which is the receptor for peptides containing the NGR motif. NGR-modified Docetaxel (DTX)-loaded PEG-b-PLGA polymeric nanoparticles (cNGR-DNB-NPs) were developed and evaluated for their in vitro potential in HT-1080 cell line. The cNGR-DNB-NPs containing particles were about 148 nm in diameter with spherical shape and high encapsulation efficiency. Cellular uptake was confirmed both qualitatively and quantitatively by Confocal Laser Scanning Microscopy (CLSM) and flow cytometry. Both quantitatively and qualitatively results confirmed the NGR conjugated nanoparticles revealed the higher uptake of nanoparticles by CD13-overexpressed tumor cells. Free NGR inhibited the cellular uptake of cNGR-DNB-NPs, revealing the mechanism of receptor mediated endocytosis. In vitro cytotoxicity studies demonstrated that cNGR-DNB-NPs, formulation was more cytotoxic than unconjugated one, which were consistent well with the observation of cellular uptake. Hence, the selective delivery of cNGR-DNB-NPs formulation in CD13-overexpressing tumors represents a potential approach for the design of nanocarrier-based dual targeted delivery systems for targeting the tumor cells and vasculature.

Keywords: solid Tumor, docetaxel, targeting, NGR ligand

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Authors: Jaewoo Choi, Ki-Tae Hwang, Eunyoung Ko

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Backgrounds/Aims: Patients with breast cancer are currently classified according to TNM stage. Nevertheless, the actual volume would be mis-estimated, and it would bring on inappropriate diagnosis. Tridimensional volume-stage derived from the ellipsoid formula was presented as useful measure. Methods: The medical records of 480 consecutive breast cancer between January 2001 and March 2013 were retrospectively reviewed. All patients were divided into three groups according to tumor volume by receiver operating characteristic analysis, and the ranges of each volume-stage were that V1 was below 2.5 cc, V2 was exceeded 2.5 and below 10.9 cc, and V3 was exceeded 10.9 cc. We analyzed outcomes of volume-stage and compared disease-free survival (DFS) and overall survival (OS) between size-stage and volume-stage with variant intrinsic factor. Results: In the T2 stage, there were patients who had a smaller volume than 4.2 cc known as maximum value of T1. These findings presented that patients in T1c had poorer DFS than T2-lesser (mean of DFS 48.7 vs. 51.8, p = 0.011). Such is also the case in OS (mean of OS 51.1 vs. 55.3, p = 0.006). The cumulative survival curves for V1, V2 compared T1, T2 showed similarity in DFS (HR 1.9 vs. 1.9), and so did it for V3 compared T3 (HR 3.5 vs. 2.6) significantly. Conclusion: This study demonstrated that tumor volume had good feasibility on the prognosis of patients with breast cancer. We proposed that volume-stage should be considered for an additional stage indicator, particularly in early breast cancer.

Keywords: breast cancer, tridimensional volume of tumor, TNM stage, volume stage

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Authors: Parag Katira, Frederika Rentzeperis, Zuzanna Nowicka, Giada Fiandaca, Thomas Veith, Jack Farinhas, Noemi Andor

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Resource limitations shape the outcome of competitions between genetically heterogeneous pre-malignant cells. One example of such heterogeneity is in the ploidy (DNA content) of pre-malignant cells. A whole-genome duplication (WGD) transforms a diploid cell into a tetraploid one and has been detected in 28-56% of human cancers. If a tetraploid subclone expands, it consistently does so early in tumor evolution, when cell density is still low, and competition for nutrients is comparatively weak – an observation confirmed for several tumor types. WGD+ cells need more resources to synthesize increasing amounts of DNA, RNA, and proteins. To quantify resource limitations and how they relate to ploidy, we performed a PAN cancer analysis of WGD, PET/CT, and MRI scans. Segmentation of >20 different organs from >900 PET/CT scans were performed with MOOSE. We observed a strong correlation between organ-wide population-average estimates of Oxygen and the average ploidy of cancers growing in the respective organ (Pearson R = 0.66; P= 0.001). In-vitro experiments using near-diploid and near-tetraploid lineages derived from a breast cancer cell line supported the hypothesis that DNA content influences Glucose- and Oxygen-dependent proliferation-, death- and migration rates. To model how subpopulations with variable DNA content compete in the resource-limited environment of the human brain, we developed a stochastic state-space model of the brain (S3MB). The model discretizes the brain into voxels, whereby the state of each voxel is defined by 8+ variables that are updated over time: stiffness, Oxygen, phosphate, glucose, vasculature, dead cells, migrating cells and proliferating cells of various DNA content, and treat conditions such as radiotherapy and chemotherapy. Well-established Fokker-Planck partial differential equations govern the distribution of resources and cells across voxels. We applied S3MB on sequencing and imaging data obtained from a primary GBM patient. We performed whole genome sequencing (WGS) of four surgical specimens collected during the 1ˢᵗ and 2ⁿᵈ surgeries of the GBM and used HATCHET to quantify its clonal composition and how it changes between the two surgeries. HATCHET identified two aneuploid subpopulations of ploidy 1.98 and 2.29, respectively. The low-ploidy clone was dominant at the time of the first surgery and became even more dominant upon recurrence. MRI images were available before and after each surgery and registered to MNI space. The S3MB domain was initiated from 4mm³ voxels of the MNI space. T1 post and T2 flair scan acquired after the 1ˢᵗ surgery informed tumor cell densities per voxel. Magnetic Resonance Elastography scans and PET/CT scans informed stiffness and Glucose access per voxel. We performed a parameter search to recapitulate the GBM’s tumor cell density and ploidy composition before the 2ⁿᵈ surgery. Results suggest that the high-ploidy subpopulation had a higher Glucose-dependent proliferation rate (0.70 vs. 0.49), but a lower Glucose-dependent death rate (0.47 vs. 1.42). These differences resulted in spatial differences in the distribution of the two subpopulations. Our results contribute to a better understanding of how genomics and microenvironments interact to shape cell fate decisions and could help pave the way to therapeutic strategies that mimic prognostically favorable environments.

Keywords: tumor evolution, intra-tumor heterogeneity, whole-genome doubling, mathematical modeling

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Authors: Xue Xiao, Sun Hao, Liu Donghua

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E-commerce is experiencing rapid development and evolution, but traditional research methods are difficult to fully demonstrate the relationship between micro factors and macro evolution in the development process of e-commerce, which cannot provide accurate assessment for the existing strategies and predict the future evolution trends. To solve these problems, this paper presents the concept of e-commerce service ecosystem based on the characteristics of e-commerce and business ecosystem theory, describes e-commerce environment as a complex adaptive system from the perspective of ecology, constructs a e-commerce service ecosystem model by using Agent-based modeling method and Java language in RePast simulation platform and conduct experiment through the way of computational experiment, attempt to provide a suitable and effective researching method for the research on e-commerce evolution. By two experiments, it can be found that system model built in this paper is able to show the evolution process of e-commerce service ecosystem and the relationship between micro factors and macro emergence. Therefore, the system model constructed by Agent-based method and computational experiment provides proper means to study the evolution of e-commerce ecosystem.

Keywords: e-commerce service ecosystem, complex system, agent-based modeling, computational experiment

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Authors: Mahmoodreza Tahamtan

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Malignant surface epithelial ovarian tumors(SEOT) account for approximately 90% of primary ovarian cancer. We evaluate the immunohistochemical expression of WT1 protein among different histologic subtypes of SEOT. Immunohistochemistry for WT1 was done on 35 serous cystadenocarcinomas, 9 borderline serous tumors. A tumor was considered negative if < 1% of tumor cells were stained.Positive reactions were graded as follows:1+,1%-24%; 2+,25%-49%; 3+,50%-74%; 4+,75%-100%. Of the 35 cases of ovarian serous cystadenocarcinoma 30(85.7%)were diffusely positive(3+,4+),4 showed reactivity of < 50% of the tumor cells(1+,2+) and one were negative. All 9 borderline serous tumors showed immunoreactivity with WT1. WT1 is a good marker to distinguish primary ovarian serous carcinomas from other surface epithelial tumors.

Keywords: WT1, ovary, malignant, epithelial tumors

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Authors: Kamila Dus-Szachniewicz, Artur Bednarkiewicz, Katarzyna Gdesz-Birula, Slawomir Drobczynski

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In modern oncology hyperthermia (HT) is defined as a controlled tumor heating. HT treatment temperatures range between 40–48 °C and can selectively damage heat-sensitive cancer cells or limit their further growth, usually with minimal injury to healthy tissues. Despite many advantages, conventional whole-body and regional hyperthermia have clinically relevant side effects, including cardiac and vascular disorders. Additionally, the lack of accessibility of deep-seated tumor sites and impaired targeting micrometastases renders HT less effective. It is believed that above disadvantages can significantly overcome by the application of biofunctionalized microparticles, which can specifically target tumor sites and become activated by an external stimulus to provide a sufficient cellular response. In our research, the unique optical tweezers system have enabled capturing the silica microparticles, primary cells and tumor spheroids in highly controllable and reproducible environment to study the impact of localized heat stimulation on normal and pathological cell and within multicellular tumor spheroid. High throughput spheroid model was introduced to better mimic the response to HT treatment on tumors in vivo. Additionally, application of local heating of tumor spheroids was performed in strictly controlled conditions resembling tumor microenvironment (temperature, pH, hypoxia, etc.), in response to localized and nonhomogeneous hyperthermia in the extracellular matrix, which promotes tumor progression and metastatic spread. The lack of precise control over these well- defined parameters in basic research leads to discrepancies in the response of tumor cells to the new treatment strategy in preclinical animal testing. The developed approach enables also sorting out subclasses of cells, which exhibit partial or total resistance to therapy, in order to understand fundamental aspects of the resistance shown by given tumor cells in response to given therapy mode and conditions. This work was funded by the National Science Centre (NCN, Poland) under grant no. UMO-2017/27/B/ST7/01255.

Keywords: cancer spheroids, hyperthermia, microparticles, optical tweezers

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Authors: R. R. Ramsheeja, R. Sreeraj

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For view the internal structures of the human body such as liver, brain, kidney etc have a wide range of different modalities for medical images are provided nowadays. Computer Tomography is one of the most significant medical image modalities. In this paper use CT liver images for study the use of automatic computer aided techniques to calculate the volume of the liver tumor. Segmentation method is used for the detection of tumor from the CT scan is proposed. Gaussian filter is used for denoising the liver image and Adaptive Thresholding algorithm is used for segmentation. Multiple Region Of Interest(ROI) based method that may help to characteristic the feature different. It provides a significant impact on classification performance. Due to the characteristic of liver tumor lesion, inherent difficulties appear selective. For a better performance, a novel proposed system is introduced. Multiple ROI based feature selection and classification are performed. In order to obtain of relevant features for Support Vector Machine(SVM) classifier is important for better generalization performance. The proposed system helps to improve the better classification performance, reason in which we can see a significant reduction of features is used. The diagnosis of liver cancer from the computer tomography images is very difficult in nature. Early detection of liver tumor is very helpful to save the human life.

Keywords: computed tomography (CT), multiple region of interest(ROI), feature values, segmentation, SVM classification

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Authors: Mohamed Shafi Bin Mahboob Ali

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Introduction: Synchronous tumor is defined as the presence of more than one primary malignant lesion in the same patient at the indexed diagnosis. It is a rare occurrence, especially in the spectrum of colorectal cancer, which accounts for less than 4%. The underlying pathology of a synchronous tumor is thought to be due to a genomic factor, which is microsatellite instability (MIS) with the involvement of BRAF, KRAS, and the GSRM1 gene. There are no specific sites of occurrence for the synchronous colorectal tumor, but many studies have shown that a synchronous tumor has about 43% predominance in the ascending colon with rarity in the sigmoid colon. Case Report: We reported a case of a young lady in the middle of her 30's with no family history of colorectal cancer that was diagnosed with a synchronous adenocarcinoma at the descending colon and rectosigmoid region. The lady's presentation was quite perplexing as she presented to the district hospital initially with simple, uncomplicated hemorrhoids and constipation. She was then referred to our center for further management as she developed a 'football' sized right gluteal swelling with a complete intestinal obstruction and bilateral lower-limb paralysis. We performed a CT scan and biopsy of the lesion, which found that the tumor engulfed the sacrococcygeal region with more than one primary lesion in the colon as well as secondaries in the liver. The patient was operated on after a multidisciplinary meeting was held. Pelvic exenteration with tumor debulking and anterior resection were performed. Postoperatively, she was referred to the oncology team for chemotherapy. She had a tremendous recovery in eight months' time with a partial regain of her lower limb power. The patient is still under our follow-up with an improved quality of life post-intervention. Discussion: Synchronous colon cancer is rare, with an incidence of 2.4% to 12.4%. It has male predominance and is pathologically more advanced compared to a single colon lesion. Down staging the disease by means of chemoradiotherapy has shown to be effective in managing this tumor. It is seen commonly on the right colon, but in our case, we found it on the left colon and the rectosigmoid. Conclusion: Managing a synchronous colon tumor could be challenging to surgeons, especially in deciding the extent of resection and postoperative functional outcomes of the bowel; thus, individual treatment strategies are needed to tackle this pathology.

Keywords: synchronous, colon, tumor, adenocarcinoma

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Authors: Hakim Derradji, M’Hammedi Yousra, Sabrou Abdelmalek, Tabet Nacer

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Introduction: This is a retrospective study carried out at the Central Hospital of Army from 2017 to 2022. Its objective is to demonstrate the best surgical method for the management of obstructive hydrocephalus secondary to a posterior fossa tumor in children, in pre, per, and post-operative. Patients and Methods: During this period, 24 children (over 1 year old) were admitted for treatment of the posterior fossa tumor with obstructive secondary hydrocephalus and the majority of whom benefited from VCS followed by surgery and excision, the rest, received after evacuation from other hospital structures, were managed there beforehand with ventriculoperitoneal diversion or external drainage. We found that the way hydrocephalus is managed has implications for subsequent management, hence the need for this study to determine the effectiveness of different surgical procedures used in the treatment of hydrocephalus in these patients. The evaluation is made on the basis of revision rate, complications, survival, and radiological evaluation. Results: 6 patients (25%) received a ventriculoperitoneal shunt (VPD), 15 patients (62%) underwent a ventriculocysternostomy (VCS), and 3 patients (12.5%) received temporary ventricular drainage before or during tumor excision. The post-operative results were almost similar. Nevertheless, a high failure rate (25%) was observed. No deaths are recorded. In total, 75% of children who had a DVP were reoperated. The revision by VCS was performed, in addition to the 4 patients benefiting from a DVP, with one patient having received external drainage, and only one revision of a VCS was recorded. In the two patients who received external drainage, restoration of CSF outflow was observed following tumor resection. Conclusion: VCS is indicated in the first intention in the treatment of hydrocephalus secondary to a posterior fossa tumor, in view of the satisfactory results obtained and the high failure rate in DVP, especially with the presence of metastatic cells in the peritoneum, but can be considered as a second-line treatment.

Keywords: posterior fossa tumor, obstructive hydrocephalus, DVP, VCS

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Authors: Haile F. Darge, Hsieh C. Tsai

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The tumor microenvironment affects the therapeutic outcomes of cancer disease. In a malignant tumor, overexpression of vascular endothelial growth factor (VEGF) provokes the production of pathologic vascular networks. This results in a hostile tumor environment that hinders anti-cancer drug activities and profoundly fuels tumor progression. In this study, we develop a strategy of sequential sustain release of the anti-angiogenic drug: Bevacizumab(BVZ), and anti-cancer drug: Doxorubicin(DOX) which had a synergistic effect on cancer treatment. Poly (D, L-Lactide)- Poly (ethylene glycol) –Poly (D, L-Lactide) (PDLLA-PEG-PDLLA) thermo-sensitive hydrogel was used as a vehicle for local delivery of drugs in a single platform. The in vitro release profiles of the drugs were investigated and confirmed a relatively rapid release of BVZ (73.56 ± 1.39%) followed by Dox (61.21 ± 0.62%) for a prolonged period. The cytotoxicity test revealed that the copolymer exhibited negligible cytotoxicity up to 2.5 mg ml-1 concentration on HaCaT and HeLa cells. The in vivo study on Hela xenograft nude mice verified that hydrogel co-loaded with BVZ and DOX displayed the highest tumor suppression efficacy for up to 36 days with pronounce anti-angiogenic effect of BVZ and with no noticeable damage on vital organs. Therefore, localized co-delivery of anti-angiogenic drug and anti-cancer drugs by the hydrogel system may be a promising approach for enhanced chemotherapeutic efficacy in cancer treatment.

Keywords: anti-angiogenesis, chemotherapy, controlled release, thermo-sensitive hydrogel

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Authors: Seyhan Karaçavuş, Bülent Yılmaz, Ömer Kayaaltı, Semra İçer, Arzu Taşdemir, Oğuzhan Ayyıldız, Kübra Eset, Eser Kaya

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In this study, our goal was to perform tumor staging and subtype determination automatically using different texture analysis approaches for a very common cancer type, i.e., non-small cell lung carcinoma (NSCLC). Especially, we introduced a texture analysis approach, called Law’s texture filter, to be used in this context for the first time. The 18F-FDG PET images of 42 patients with NSCLC were evaluated. The number of patients for each tumor stage, i.e., I-II, III or IV, was 14. The patients had ~45% adenocarcinoma (ADC) and ~55% squamous cell carcinoma (SqCCs). MATLAB technical computing language was employed in the extraction of 51 features by using first order statistics (FOS), gray-level co-occurrence matrix (GLCM), gray-level run-length matrix (GLRLM), and Laws’ texture filters. The feature selection method employed was the sequential forward selection (SFS). Selected textural features were used in the automatic classification by k-nearest neighbors (k-NN) and support vector machines (SVM). In the automatic classification of tumor stage, the accuracy was approximately 59.5% with k-NN classifier (k=3) and 69% with SVM (with one versus one paradigm), using 5 features. In the automatic classification of tumor subtype, the accuracy was around 92.7% with SVM one vs. one. Texture analysis of FDG-PET images might be used, in addition to metabolic parameters as an objective tool to assess tumor histopathological characteristics and in automatic classification of tumor stage and subtype.

Keywords: cancer stage, cancer cell type, non-small cell lung carcinoma, PET, texture analysis

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Authors: Mahesh Pal, Tripti Mishra, Chandana Rao, Dalip Upreti

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Cancer has been considered to be a very dreadful disease. Holmskioldia sanguinea is a large climbing shrub found in the Himalayas at an altitude of 5,000 ft and preliminary investigation showed the excellent yield of andrographolide and subjected for the anticancer activity. Protective effect of Holmskioldia sanguinea leaf ethanolic extract has been investigated against Ehrlich ascites carcinoma (EAC) and Daltons ascites lymphoma (DAL) in Swiss albino mice to evaluate the possible mechanism of action. The enzymatic antioxidant status was studied on tumor bearing mice, which shows the potential of the compound to possess significant free radical scavenging property and revealed significant tumor regression and prolonged survival time. The isolated bioactive molecule andrographolide from Holmskioldia sanguinea yields (2.5%) in subject to HPTLC/HPLC analysis. The cellular defense system constituting the superoxide dismutase, catalyses was enhanced whereby the lipid peroxidation content was restricted to a larger extent. The Holmskioldia sanguinea is a new source of andrographolide and demonstrated the potency in treatment of cancer.

Keywords: Holmskioldia sanguinea, tumor, mice, andrographolide

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Authors: S. Ravichandra, D. V. L. N. Somayajulu

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Requirement of stakeholders for adding more details to the database is the main cause of the schema evolution in the relational database. Further, this schema evolution causes the instability to the database. Hence, it is aimed to define a metric suite for schema evolution of a relational database. The metric suite will calculate the metrics based on the features of the database, analyse the queries on the database and measures the coupling, cohesion and component dependencies of the schema for existing and evolved versions of the database. This metric suite will also provide an indicator for the problems related to the stability and usability of the evolved database. The degree of change in the schema of a database is presented in the forms of graphs that acts as an indicator and also provides the relations between various parameters (metrics) related to the database architecture. The acquired information is used to defend and improve the stability of database architecture. The challenges arise in incorporating these metrics with varying parameters for formulating a suitable metric suite are discussed. To validate the proposed metric suite, an experimentation has been performed on publicly available datasets.

Keywords: cohesion, coupling, entropy, metric suite, schema evolution

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Authors: F. Kashanian, M. M. Masoudi, A. Akbari, A. Shamloo, M. R. Zand, S. S. Salehi

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Nano-sized materials present new opportunities in biology and medicine and they are used as biomedical tools for investigation, separation of molecules and cells. To achieve more effective cancer therapy, it is essential to select cancer cells exactly. This research suggests that using the antibody-functionalized nontoxic Arginine-doped magnetic nanoparticles (A-MNPs), has been prosperous in detection, capture, and magnetic separation of circulating tumor cells (CTCs) in tumor tissue. In this study, A-MNPs were synthesized via a simple precipitation reaction and directly immobilized Ep-CAM EBA-1 antibodies over superparamagnetic A-MNPs for Mucin BCA-225 in breast cancer cell. The samples were characterized by vibrating sample magnetometer (VSM), FT-IR spectroscopy, Tunneling Electron Microscopy (TEM) and Scanning Electron Microscopy (SEM). These antibody-functionalized nontoxic A-MNPs were used to capture breast cancer cell. Through employing a strong permanent magnet, the magnetic separation was achieved within a few seconds. Antibody-Conjugated nontoxic Arginine-doped Fe₃O₄ nanoparticles have the potential for the future study to capture CTCs which are released from tumor tissue and for drug delivery, and these results demonstrate that the antibody-conjugated A-MNPs can be used in magnetic hyperthermia techniques for cancer treatment.

Keywords: tumor tissue, antibody, magnetic nanoparticle, CTCs capturing

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Authors: Michael Aupetit, Mahmoud Al-ismail, Khaled Mohamed

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Cancer is a major public health problem all over the world. Breast cancer has the highest incidence rate over all cancers for women in Qatar making its study a top priority of the country. Human cancer is a dynamic disease that develops over an extended period through the accumulation of a series of genetic alterations. A Darwinian process drives the tumor cells toward higher malignancy growing the branches of a progression tree in the space of genes expression. Although it is not possible to track these genetic alterations dynamically for one patient, it is possible to reconstruct the progression tree from the aggregation of thousands of tumor cells’ genetic profiles from thousands of different patients at different stages of the disease. Analyzing the progression tree is a way to detect pivotal molecular events that drive the malignant evolution and to provide a guide for the development of cancer diagnostics, prognostics and targeted therapeutics. In this work we present the development of a Visual Analytic web platform CanVis enabling users to upload gene-expression data and analyze their progression tree. The server computes the progression tree based on state-of-the-art techniques and allows an interactive visual exploration of this tree and the gene-expression data along its branching structure helping to discover potential driver genes.

Keywords: breast cancer, progression tree, visual analytics, web platform

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Authors: Akram Boubakri, Fethi Choubani, Tan Hoa Vuong, Jacques David

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Nowadays, microwave hyperthermia is considered as an effective treatment for the malignant tumors. This microwave treatment which comes to substitute the chemotherapy and the surgical intervention enables an in-depth tumor heating without causing any diseases to the sane tissue. This technique requires a high precision system, in order to effectively concentrate the heating just in the tumor, without heating any surrounding healthy tissue. In the hyperthermia treatment, the temperature in cancerous area is typically raised up to over 42◦C and maintained for one hour in order to destroy the tumor sufficiently, whilst in the surrounding healthy tissues, the temperature is maintained below 42◦C to avoid any damage. Metamaterial lenses are widely used in medical applications like microwave hyperthermia treatment. They enabled a subdiffraction resolution thanks to the amplification of the evanescent waves and they can focus electromagnetic waves from a point source to a point image. Metasurfaces have been used to built metamaterial lenses. The main mechanical advantages of those structures over three dimensional material structures are ease of fabrication and a smaller required volume. Here in this work, we proposed a metasurface based lens operating at the frequency of 6 GHz and designed for microwave hyperthermia. This lens was applied and showed good results in focusing and heating the tumor inside a breast tissue with an increased and maintained temperature above 42°C. The tumor was placed in the focal distance of the lens so that only the tumor tissue will be heated. Finally, in this work, it has been shown that the hyperthermia area within the tissue can be carefully adjusted by moving the antennas or by changing the thickness of the metamaterial lenses based on the tumor position. Even though the simulations performed in this work have taken into account an ideal case, some real characteristics can be considered to improve the obtained results in a realistic model.

Keywords: focusing, hyperthermia, metamaterial lenses, metasurface, microwave treatment

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Authors: Kolja Them, Priyal Chikhaliwala, Sudeshna Chandra

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Purpose: The purpose of this work is to examine possibilities for noninvasive imaging and identification of tumor markers for cancer diagnosis. The proposed method uses antibody conjugated iron oxide nanoparticles and multicolor Magnetic Particle Imaging (mMPI). The method has the potential for radiation exposure free real-time estimation of local tumor marker concentrations in vivo. In this study, the method is applied to human Alpha-1-Fetoprotein. Materials and Methods: As tracer material AFP antibody-conjugated Dendrimer-Fe3O4 nanoparticles were used. The nanoparticle bioconjugates were then incubated with bovine serum albumin (BSA) to block any possible nonspecific binding sites. Parts of the resulting solution were then incubated with AFP antigen. MPI measurements were done using the preclinical MPI scanner (Bruker Biospin MRI GmbH) and the multicolor method was used for image reconstruction. Results: In multicolor MPI images the nanoparticles incubated only with BSA were clearly distinguished from nanoparticles incubated with BSA and AFP antigens. Conclusion: Tomographic imaging of human tumor marker Alpha-1-Fetoprotein is possible using AFP antibody conjugated iron oxide nanoparticles in presence of BSA. This opens interesting perspectives for cancer diagnosis.

Keywords: noninvasive imaging, tumor antigens, antibody conjugated iron oxide nanoparticles, multicolor magnetic particle imaging, cancer diagnosis

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Authors: Antonios Katsianis

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I present the evolution of the galaxy Star Formation Rate Function (SFRF), star formation rate-stellar mass relation (SFR-M*) and Cosmic Star Formation Rate Density (CSFRD) of z = 0-8 galaxies employing both the Evolution and Assembly of GaLaxies and their Environments (EAGLE) simulations and a compilation of UV, Ha, radio and IR data. While I present comparisons between the above, I evaluate the effect and importance of supernovae/active galactic nuclei feedback. The relation between the star formation rate and stellar mass of galaxies represents a fundamental constraint on galaxy formation, and has been studied extensively both in observations and cosmological hydrodynamic simulations. However, a tension between the above is reported in the literature. I present the evolution of the SFR-M* relation and demonstrate the inconsistencies between observations that are retrieved using different methods. I employ cosmological hydrodynamic simulations combined with radiative transfer methods and compare these with a range of observed data in order to investigate further the root of this tension. Last, I present insights about the scatter of the SFR-M* relation and investigate which mechanisms (e.g. feedback) drive its shape and evolution.

Keywords: cosmological simulations, galaxy formation and evolution, star formation rate, stellar masses

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Authors: Ren-Jy Ben, Jo-Chi Jao, Chiu-Ya Liao, Ya-Ru Tsai, Lain-Chyr Hwang, Po-Chou Chen

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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 study 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 thigh 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. And 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 rabbits. Afterwards, 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 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.

Keywords: doxorubicin, dynamic contrast-enhanced MRI, lipodox, magnetic resonance imaging, VX2 tumor model

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Authors: Han Xiao

Abstract:

The development of nanomedicines has recently achieved several breakthroughs in the field of cancer treatment; however, the biocompatibility and targeted burst release of these medications remain a limitation, which leads to serious side effects and significantly narrows the scope of their applications. The self-assembly of intermediate filament protein (IFP) peptides was triggered by a hydrophobic cation drug 7-amino actinomycin D (7-AAD) to synthesize pH-activatable nanoparticles (NPs) that could simultaneously locate tumors and produce antitumor effects. The designed IFP peptide included a target peptide (arginine–glycine–aspartate), a negatively charged region, and an α-helix sequence. It also possessed the ability to encapsulate 7-AAD molecules through the formation of hydrogen bonds and hydrophobic interactions by a one-step method. 7-AAD molecules with excellent near-infrared fluorescence properties could be target delivered into tumor cells by NPs and released immediately in the acidic environments of tumors and endosome/lysosomes, ultimately inducing cytotoxicity by arresting the tumor cell cycle with inserted DNA. It is noteworthy that the IFP/7-AAD NPs tail vein injection approach demonstrated not only high tumor-targeted imaging potential, but also strong antitumor therapeutic effects in vivo. The proposed strategy may be used in the delivery of cationic antitumor drugs for precise imaging and cancer therapy.

Keywords: 7-amino actinomycin D, intermediate filament protein, nanoparticle, tumor image

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Authors: Mounir Zekkaoui, Abdelhadi Fennan

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The software evolution control requires a deep understanding of the changes and their impact on different system heterogeneous artifacts. And an understanding of descriptive knowledge of the developed software artifacts is a prerequisite condition for the success of the evolutionary process. The implementation of an evolutionary process is to make changes more or less important to many heterogeneous software artifacts such as source code, analysis and design models, unit testing, XML deployment descriptors, user guides, and others. These changes can be a source of degradation in functional, qualitative or behavioral terms of modified software. Hence the need for a unified approach for extraction and representation of different heterogeneous artifacts in order to ensure a unified and detailed description of heterogeneous software artifacts, exploitable by several software tools and allowing to responsible for the evolution of carry out the reasoning change concerned.

Keywords: heterogeneous software artifacts, software evolution control, unified approach, meta model, software architecture

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Authors: Shouta Sora, Shizuki Kuriu, Radhika Mishra, Ariunbuyan Sukhbaatar, Maya Sakamoto, Shiro Mori, Tetsuya Kodama

Abstract:

Lymph node (LN) metastasis accounts for 20 - 30 % of all deaths in patients with head and neck cancer. Therefore, the control of metastatic lymph nodes (MLNs) is necessary to improve the life prognosis of patients with cancer. In a classical metastatic theory, tumor cells are thought to metastasize hematogenously through a bead-like network of lymph nodes. Recently, a lymph node-mediated hematogenous metastasis theory has been proposed, in which sentinel LNs are regarded as a source of distant metastasis. Therefore, the treatment of MLNs at the early stage is essential to prevent distant metastasis. Radiation therapy is one of the primary therapeutic modalities in cancer treatment. In addition, total body irradiation (TBI) has been reported to act as activation of natural killer cells and increase of infiltration of CD4+ T-cells to tumor tissues. However, the treatment effect of TBI for MLNs remains unclear. This study evaluated the possibilities of low-dose total body irradiation (L-TBI) and middle-dose total body irradiation (M-TBI) for the treatment of MLNs. Mouse breast cancer FM3A-Luc cells were injected into subiliac lymph node (SiLN) of MXH10/Mo/LPR mice to induce the metastasis to the proper axillary lymph node (PALN) and lung. Mice were irradiated for the whole body on 4 days after tumor injection. The L-TBI and M-TBI were defined as irradiations to the whole body at 0.2 Gy and 1.0 Gy, respectively. Tumor growth was evaluated by in vivo bioluminescence imaging system. In the non-irradiated group, tumor activities on SiLN and PALN significantly increased over time, and the metastasis to the lung from LNs was confirmed 28 days after tumor injection. The L-TBI led to a tumor growth delay in PALN but did not control tumor growth in SiLN and metastasis to the lung. In contrast, it was found that the M-TBI significantly delayed the tumor growth of both SiLN and PALN and controlled the distant metastasis to the lung compared with non-irradiated and L-TBI groups. These results suggest that the M-TBI is an effective treatment method for MLNs in the early stage and distant metastasis from lymph nodes via blood vessels connected with LNs.

Keywords: metastatic lymph node, lung metastasis, radiation therapy, total body irradiation, lymphatic system

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Authors: Eashwar V. Somasundaram, Raoul R. Wadhwa, Jacob G. Scott

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The use of radiomics in measuring geometric properties of tumor images such as size, surface area, and volume has been invaluable in assessing cancer diagnosis, treatment, and prognosis. In addition to analyzing geometric properties, radiomics would benefit from measuring topological properties using persistent homology. Intuitively, features uncovered by persistent homology may correlate to tumor structural features. One example is necrotic cavities (corresponding to 2D topological features), which are markers of very aggressive tumors. We develop a data pipeline in R that clusters tumors images based on persistent homology is used to identify meaningful clinical distinctions between tumors and possibly new relationships not captured by established clinical categorizations. A preliminary analysis was performed on 16 Magnetic Resonance Imaging (MRI) breast tissue segments downloaded from the 'Investigation of Serial Studies to Predict Your Therapeutic Response with Imaging and Molecular Analysis' (I-SPY TRIAL or ISPY1) collection in The Cancer Imaging Archive. Each segment represents a patient’s breast tumor prior to treatment. The ISPY1 dataset also provided the estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) status data. A persistent homology matrix up to 2-dimensional features was calculated for each of the MRI segmentation. Wasserstein distances were then calculated between all pairwise tumor image persistent homology matrices to create a distance matrix for each feature dimension. Since Wasserstein distances were calculated for 0, 1, and 2-dimensional features, three hierarchal clusters were constructed. The adjusted Rand Index was used to see how well the clusters corresponded to the ER/PR/HER2 status of the tumors. Triple-negative cancers (negative status for all three receptors) significantly clustered together in the 2-dimensional features dendrogram (Adjusted Rand Index of .35, p = .031). It is known that having a triple-negative breast tumor is associated with aggressive tumor growth and poor prognosis when compared to non-triple negative breast tumors. The aggressive tumor growth associated with triple-negative tumors may have a unique structure in an MRI segmentation, which persistent homology is able to identify. This preliminary analysis shows promising results in the use of persistent homology on tumor imaging to assess the severity of breast tumors. The next step is to apply this pipeline to other tumor segment images from The Cancer Imaging Archive at different sites such as the lung, kidney, and brain. In addition, whether other clinical parameters, such as overall survival, tumor stage, and tumor genotype data are captured well in persistent homology clusters will be assessed. If analyzing tumor MRI segments using persistent homology consistently identifies clinical relationships, this could enable clinicians to use persistent homology data as a noninvasive way to inform clinical decision making in oncology.

Keywords: cancer biology, oncology, persistent homology, radiomics, topological data analysis, tumor imaging

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Authors: V. R. Ahire, A. Kumar, B. N. Pandey, K. P. Mishra, G. R. Kulkarni

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Radiation therapy is an effective vital strategy used globally in the treatment of cervical cancer. However, radiation efficacy principally depends on the radiosensitivity of the tumor, and not all patient exhibit significant response to irradiation. A radiosensitive tumor is easier to cure than a radioresistant tumor which later advances to local recurrence and metastasis. Herbal polyphenols are gaining attention for exhibiting radiosensitization through various signaling. Current work focuses to study the radiosensitization effect of ellagic acid (EA), on HeLa cells. EA intermediated radiosensitization of HeLa cells was due to the induction γ-H2AX foci formation, G1 phase cell cycle arrest, and loss of reproductive potential, growth inhibition, drop in the mitochondrial membrane potential and protein expression studies that eventually induced apoptosis. Irradiation of HeLa in presence of EA (10 μM) to doses of 2 and 4 Gy γ-radiation produced marked tumor cytotoxicity. EA also demonstrated radio-protective effect on normal cell, NIH3T3 and aided recovery from the radiation damage. Our results advocate EA to be an effective adjuvant for improving cancer radiotherapy as it displays striking tumor cytotoxicity and reduced normal cell damage instigated by irradiation.

Keywords: apoptotic radiosensitivity, ellagic acid, mitochondrial potential, cell-cycle arrest

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Authors: Sajeeha Ansar, Asad Ali Safi, Sheikh Ziauddin, Ahmad R. Shahid, Faraz Ahsan

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Gliomas are most challenging and aggressive type of tumors which appear in different sizes, locations, and scattered boundaries. CNN is most efficient deep learning approach with outstanding capability of solving image analysis problems. A fully automatic deep learning based 2D-CNN model for brain tumor segmentation is presented in this paper. We used small convolution filters (3 x 3) to make architecture deeper. We increased convolutional layers for efficient learning of complex features from large dataset. We achieved better results by pushing convolutional layers up to 16 layers for HGG model. We achieved reliable and accurate results through fine-tuning among dataset and hyper-parameters. Pre-processing of this model includes generation of brain pipeline, intensity normalization, bias correction and data augmentation. We used the BRATS-2015, and Dice Similarity Coefficient (DSC) is used as performance measure for the evaluation of the proposed method. Our method achieved DSC score of 0.81 for complete, 0.79 for core, 0.80 for enhanced tumor regions. However, these results are comparable with methods already implemented 2D CNN architecture.

Keywords: brain tumor segmentation, convolutional neural networks, deep learning, HGG

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Authors: Abraham J. Rizkalla, Tristan D. Yan

Abstract:

Atrial myxoma is the most common primary cardiac tumor, and can result in cardiac failure secondary to obstruction, or systemic embolism due to fragmentation. Traditionally, excision of atrial an myxoma has been performed through median sternotomy, however the robotic approach offers several advantages including less pain, improved cosmesis, and faster recovery. Here, we highlight the less well recognized advantages and technical aspects to robotic myxoma resection. This video-presentation demonstrates the resection of a papillary subtype left atrial myxoma using the DaVinci© Xi surgical robot. The 10x magnification and 3D vision allows for the interface between the tumor and the interatrial septum to be accurately dissected, without the need to patch the interatrial septum. Several techniques to avoid tumor fragmentation and embolization are demonstrated throughout the procedure. The tumor was completely excised with clear margins. There was no atrial septal defect or mitral valve injury on post operative transesophageal echocardiography. The patient was discharged home on the fourth post-operative day. This video-presentation highlights the advantages of the robotic approach in atrial myxoma resection compared with sternotomy, as well as emphasizing several technical considerations to avoid potential complications.

Keywords: cardiac surgery, left atrial myxoma, cardiac tumour, robotic resection

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Authors: Babak Masoomian, Masoud Khorrami Nejad, Hamid Riazi Esfahani

Abstract:

Purpose: To report the result of strabismus surgery in eye-salvaged retinoblastoma (Rb) patients. Methods: A retrospective case series including 18 patients with Rb and strabismus who underwent strabismus surgery after completing tumor treatment by a single pediatric ophthalmologist. Results: A total of 18 patients (10 females and 8 males) were included with a mean age of 13.3 ± 3.0 (range, 2-39) months at the time tumor presentation and 6.0 ± 1.5 (range, 4-9) years at the time of strabismus surgery. Ten (56%) patients had unilateral, and 8(44%) had bilateral involvement, and the most common worse eye tumor’s group was D (n=11), C (n=4), B (n=2) and E (n=1). Macula was involved by the tumors in 12 (67%) patients. The tumors were managed by intravenous chemotherapy (n=8, 47%), intra-arterial chemotherapy (n=7, 41%) and both (n=3, 17%). After complete treatment, the average time to strabismus surgery was 29.9 ± 20.5 (range, 12-84) months. Except for one, visual acuity was equal or less than 1.0 logMAR (≤ 20/200) in the affected eye. Seven (39%) patients had exotropia, 11(61%) had esotropia (P=0.346) and vertical deviation was found in 8 (48%) cases. The angle of deviation was 42.0 ± 10.4 (range, 30-60) prism diopter (PD) for esotropic and 35.7± 7.9 (range, 25-50) PD for exotropic patients (P=0.32) that after surgery significantly decreased to 8.5 ± 5.3 PD in esotropic cases and 5.9±6.7 PD in exotropic cases (P<0.001). The mean follow-up after surgery was 15.2 ± 2.0 (range, 10-24) months, in which 3 (17%) patients needed a second surgery. Conclusion: Strabismus surgery in treated Rb is safe, and results of the surgeries are acceptable and close to the general population. There was not associated with tumor recurrence or metastasis.

Keywords: retinoblastoma, strabismus, chemotherapy, surgery

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