Search results for: tumor infiltrating lymphocytes

Authors: H. Feza Carlak, N. G. Gencer

Abstract:

To increase the temperature contrast in thermal images, the characteristics of the electrical conductivity and thermal imaging modalities can be combined. In this experimental study, it is objected to observe whether the temperature contrast created by the tumor tissue can be improved just due to the current application within medical safety limits. Various thermal breast phantoms are developed to simulate the female breast tissue. In vitro experiments are implemented using a thermal infrared camera in a controlled manner. Since experiments are implemented in vitro, there is no metabolic heat generation and blood perfusion. Only the effects and results of the electrical stimulation are investigated. Experimental study is implemented with two-dimensional models. Temperature contrasts due to the tumor tissues are obtained. Cancerous tissue is determined using the difference and ratio of healthy and tumor images. 1 cm diameter single tumor tissue causes almost 40 °mC temperature contrast on the thermal-breast phantom. Electrode artifacts are reduced by taking the difference and ratio of background (healthy) and tumor images. Ratio of healthy and tumor images show that temperature contrast is increased by the current application.

Keywords: medical diagnostic imaging, breast phantom, active thermography, breast cancer detection

Procedia PDF Downloads 428

Authors: Ella Tyuryumina, Alexey Neznanov

Abstract:

This study is an attempt to obtain reliable data on the natural history of breast cancer growth. We analyze the opportunities for using classical mathematical models (exponential and logistic tumor growth models, Gompertz and von Bertalanffy tumor growth models) to try to describe growth of the primary tumor and the secondary distant metastases of human breast cancer. The research aim is to improve predicting accuracy of breast cancer progression using an original mathematical model referred to CoMPaS and corresponding software. We are interested in: 1) modelling the whole natural history of the primary tumor and the secondary distant metastases; 2) developing adequate and precise CoMPaS which reflects relations between the primary tumor and the secondary distant metastases; 3) analyzing the CoMPaS scope of application; 4) implementing the model as a software tool. The foundation of the CoMPaS is the exponential tumor growth model, which is described by determinate nonlinear and linear equations. The CoMPaS corresponds to TNM classification. It allows to calculate different growth periods of the primary tumor and the secondary distant metastases: 1) ‘non-visible period’ for the primary tumor; 2) ‘non-visible period’ for the secondary distant metastases; 3) ‘visible period’ for the secondary distant metastases. The CoMPaS is validated on clinical data of 10-years and 15-years survival depending on the tumor stage and diameter of the primary tumor. The new predictive tool: 1) is a solid foundation to develop future studies of breast cancer growth models; 2) does not require any expensive diagnostic tests; 3) is the first predictor which makes forecast using only current patient data, the others are based on the additional statistical data. The CoMPaS model and predictive software: a) fit to clinical trials data; b) detect different growth periods of the primary tumor and the secondary distant metastases; c) make forecast of the period of the secondary distant metastases appearance; d) have higher average prediction accuracy than the other tools; e) can improve forecasts on survival of breast cancer and facilitate optimization of diagnostic tests. The following are calculated by CoMPaS: the number of doublings for ‘non-visible’ and ‘visible’ growth period of the secondary distant metastases; tumor volume doubling time (days) for ‘non-visible’ and ‘visible’ growth period of the secondary distant metastases. The CoMPaS enables, for the first time, to predict ‘whole natural history’ of the primary tumor and the secondary distant metastases growth on each stage (pT1, pT2, pT3, pT4) relying only on the primary tumor sizes. Summarizing: a) CoMPaS describes correctly the primary tumor growth of IA, IIA, IIB, IIIB (T1-4N0M0) stages without metastases in lymph nodes (N0); b) facilitates the understanding of the appearance period and inception of the secondary distant metastases.

Keywords: breast cancer, exponential growth model, mathematical model, metastases in lymph nodes, primary tumor, survival

Procedia PDF Downloads 341

Authors: Javad Khoshnegah, Hossein Nourani, Ali Mirshahi

Abstract:

A 12-year-old female Terrier presented with lethargy, decreased appetite, melena, polyuria and polydipsia. On physical examination skin lesions including crusting, erythema and pupolopustular lesions, were observed mainly on the abdomen. Based on blood examinations, ultrasonography, necropsy and histopathological findings, the condition was diagnosed as superficial necrolytic dermatitis. Gross necropsy revealed hepatomegaly (severe vacuolar change of the hepatocytes) and a 5×5 mass adjusent to mesenteric lymph nodes which is finally diagnosed as tumor. Immunohistochemical analysis of the neoplastic cells revealed that the tumor was a glucagonoma.

Keywords: dog, glucagonoma, immunohistochemistry, tumor

Procedia PDF Downloads 235

Authors: Mostafa Sefidgar, Sohrab Zendehboudi, Hossein Bazmara, Madjid Soltani

Abstract:

Based on findings from clinical applications, most drug treatments fail to eliminate malignant tumors completely even though drug delivery through systemic administration may inhibit their growth. Therefore, better understanding of tumor formation is crucial in developing more effective therapeutics. For this purpose, nowadays, solid tumor modeling and simulation results are used to predict how therapeutic drugs are transported to tumor cells by blood flow through capillaries and tissues. A solid tumor is investigated as a porous media for fluid flow simulation. Most of the studies use Darcy model for porous media. In Darcy model, the fluid friction is neglected and a few simplified assumptions are implemented. In this study, the effect of these assumptions is studied by considering Brinkman model. A multi scale mathematical method which calculates fluid flow to a solid tumor is used in this study to investigate how neglecting fluid friction affects the solid tumor simulation. In this work, the mathematical model in our previous studies is developed by considering two model of momentum equation for porous media: Darcy and Brinkman. The mathematical method involves processes such as fluid flow through solid tumor as porous media, extravasation of blood flow from vessels, blood flow through vessels and solute diffusion, convective transport in extracellular matrix. The sprouting angiogenesis model is used for generating capillary network and then fluid flow governing equations are implemented to calculate blood flow through the tumor-induced capillary network. Finally, the two models of porous media are used for modeling fluid flow in normal and tumor tissues in three different shapes of tumors. Simulations of interstitial fluid transport in a solid tumor demonstrate that the simplifications used in Darcy model affect the interstitial velocity and Brinkman model predicts a lower value for interstitial velocity than the values that Darcy model does.

Keywords: solid tumor, porous media, Darcy model, Brinkman model, drug delivery

Procedia PDF Downloads 306

Authors: E. Solfaroli Camillocci, C. Mancini-Terracciano, V. Bocci, A. Carollo, M. Colandrea, F. Collamati, M. Cremonesi, M. E. Ferrari, P. Ferroli, F. Ghielmetti, C. M. Grana, M. Marafini, S. Morganti, M. Patane, G. Pedroli, B. Pollo, L. Recchia, A. Russomando, M. Schiariti, M. Toppi, G. Traini, R. Faccini

Abstract:

A Radio-Guided Surgery technique exploiting β− emitting radio-tracers has been suggested to overcome the impact of the large penetration of γ radiation. The detection of electrons in low radiation background provides a clearer delineation of the margins of lesioned tissues. As a start, the clinical cases were selected between the tumors known to express receptors to a β− emitting radio-tracer: 90Y-labelled DOTATOC. The results of tests on ex-vivo specimens of meningioma brain tumor and abdominal neuroendocrine tumors are presented. Voluntary patients were enrolled according to the standard uptake value (SUV > 2 g/ml) and the expected tumor-to-non-tumor ratios (TNR∼10) estimated from PET images after administration of 68Ga-DOTATOC. All these tests validated this technique yielding a significant signal on the bulk tumor and a negligible background from the nearby healthy tissue. Even injecting as low as 1.4 MBq/kg of radiotracer, tumor remnants of 0.1 ml would be detectable. The negligible medical staff exposure was confirmed and among the biological wastes only urine had a significant activity.

Keywords: ex-vivo test, meningioma, neuroendocrine tumor, radio-guided surgery

Procedia PDF Downloads 294

Authors: Dimitrios Binas, Marianna Konidari, Charis Bourgioti, Lia Angela Moulopoulou, Theodore Economopoulos, George Matsopoulos

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High grade ovarian epithelial cancer (OEC) is fatal gynecological cancer and the poor prognosis of this entity is closely related to considerable intratumoral genetic heterogeneity. By examining imaging data, it is possible to assess the heterogeneity of tumorous tissue. This study proposes a methodology for aligning, segmenting and finally visualizing information from various magnetic resonance imaging series in order to construct 3D models of heterogeneity maps from the same tumor in OEC patients. The proposed system may be used as an adjunct digital tool by health professionals for personalized medicine, as it allows for an easy visual assessment of the heterogeneity of the examined tumor.

Keywords: image segmentation, ovarian epithelial cancer, quantitative characteristics, image registration, tumor visualization

Procedia PDF Downloads 211

Authors: Ibtihal D. Mustafa, Mawia A. Hassan

Abstract:

Tumor segmentation from MRI image is important part of medical images experts. This is particularly a challenging task because of the high assorting appearance of tumor tissue among different patients. MRI images are advance of medical imaging because it is give richer information about human soft tissue. There are different segmentation techniques to detect MRI brain tumor. In this paper, different procedure segmentation methods are used to segment brain tumors and compare the result of segmentations by using correlation and structural similarity index (SSIM) to analysis and see the best technique that could be applied to MRI image.

Keywords: MRI, segmentation, correlation, structural similarity

Procedia PDF Downloads 410

Authors: Ella Tyuryumina, Alexey Neznanov

Abstract:

Finding algorithms to predict the growth of tumors has piqued the interest of researchers ever since the early days of cancer research. A number of studies were carried out as an attempt to obtain reliable data on the natural history of breast cancer growth. Mathematical modeling can play a very important role in the prognosis of tumor process of breast cancer. However, mathematical models describe primary tumor growth and metastases growth separately. Consequently, we propose a mathematical growth model for primary tumor and primary metastases which may help to improve predicting accuracy of breast cancer progression using an original mathematical model referred to CoM-IV and corresponding software. We are interested in: 1) modelling the whole natural history of primary tumor and primary metastases; 2) developing adequate and precise CoM-IV which reflects relations between PT and MTS; 3) analyzing the CoM-IV scope of application; 4) implementing the model as a software tool. The CoM-IV is based on exponential tumor growth model and consists of a system of determinate nonlinear and linear equations; corresponds to TNM classification. It allows to calculate different growth periods of primary tumor and primary metastases: 1) ‘non-visible period’ for primary tumor; 2) ‘non-visible period’ for primary metastases; 3) ‘visible period’ for primary metastases. The new predictive tool: 1) is a solid foundation to develop future studies of breast cancer models; 2) does not require any expensive diagnostic tests; 3) is the first predictor which makes forecast using only current patient data, the others are based on the additional statistical data. Thus, the CoM-IV model and predictive software: a) detect different growth periods of primary tumor and primary metastases; b) make forecast of the period of primary metastases appearance; c) have higher average prediction accuracy than the other tools; d) can improve forecasts on survival of BC and facilitate optimization of diagnostic tests. The following are calculated by CoM-IV: the number of doublings for ‘nonvisible’ and ‘visible’ growth period of primary metastases; tumor volume doubling time (days) for ‘nonvisible’ and ‘visible’ growth period of primary metastases. The CoM-IV enables, for the first time, to predict the whole natural history of primary tumor and primary metastases growth on each stage (pT1, pT2, pT3, pT4) relying only on primary tumor sizes. Summarizing: a) CoM-IV describes correctly primary tumor and primary distant metastases growth of IV (T1-4N0-3M1) stage with (N1-3) or without regional metastases in lymph nodes (N0); b) facilitates the understanding of the appearance period and manifestation of primary metastases.

Keywords: breast cancer, exponential growth model, mathematical modelling, primary metastases, primary tumor, survival

Procedia PDF Downloads 334

Authors: Ella Tyuryumina, Alexey Neznanov

Abstract:

This paper is devoted to mathematical modelling of the progression and stages of breast cancer. We propose Consolidated mathematical growth model of primary tumor and secondary distant metastases growth in patients with lymph nodes metastases (CoM-III) as a new research tool. We are interested in: 1) modelling the whole natural history of primary tumor and secondary distant metastases growth in patients with lymph nodes metastases; 2) developing adequate and precise CoM-III which reflects relations between primary tumor and secondary distant metastases; 3) analyzing the CoM-III scope of application; 4) implementing the model as a software tool. Firstly, the CoM-III includes exponential tumor growth model as a system of determinate nonlinear and linear equations. Secondly, mathematical model corresponds to TNM classification. It allows to calculate different growth periods of primary tumor and secondary distant metastases growth in patients with lymph nodes metastases: 1) ‘non-visible period’ for primary tumor; 2) ‘non-visible period’ for secondary distant metastases growth in patients with lymph nodes metastases; 3) ‘visible period’ for secondary distant metastases growth in patients with lymph nodes metastases. The new predictive tool: 1) is a solid foundation to develop future studies of breast cancer models; 2) does not require any expensive diagnostic tests; 3) is the first predictor which makes forecast using only current patient data, the others are based on the additional statistical data. Thus, the CoM-III model and predictive software: a) detect different growth periods of primary tumor and secondary distant metastases growth in patients with lymph nodes metastases; b) make forecast of the period of the distant metastases appearance in patients with lymph nodes metastases; c) have higher average prediction accuracy than the other tools; d) can improve forecasts on survival of breast cancer and facilitate optimization of diagnostic tests. The following are calculated by CoM-III: the number of doublings for ‘non-visible’ and ‘visible’ growth period of secondary distant metastases; tumor volume doubling time (days) for ‘non-visible’ and ‘visible’ growth period of secondary distant metastases. The CoM-III enables, for the first time, to predict the whole natural history of primary tumor and secondary distant metastases growth on each stage (pT1, pT2, pT3, pT4) relying only on primary tumor sizes. Summarizing: a) CoM-III describes correctly primary tumor and secondary distant metastases growth of IA, IIA, IIB, IIIB (T1-4N1-3M0) stages in patients with lymph nodes metastases (N1-3); b) facilitates the understanding of the appearance period and inception of secondary distant metastases.

Keywords: breast cancer, exponential growth model, mathematical model, primary tumor, secondary metastases, survival

Procedia PDF Downloads 302

Authors: Wan-Ting Kuo, Yi-Wen Liu, Hsiao-Sheng Liu

Abstract:

Annual incidence of bladder cancer increases in the world and occurs frequently in the male. Most common type is transitional cell carcinoma (TCC) which is treated by transurethral resection followed by intravesical administration of agents. In clinical treatment of bladder cancer, chemotherapeutic drugs-induced apoptosis is always used in patients. However, cancers usually develop resistance to chemotherapeutic drugs and often lead to aggressive tumors with worse clinical outcomes. Approximate 70% TCC recurs and 30% recurrent tumors progress to high-grade invasive tumors, indicating that new therapeutic agents are urgently needed to improve the successful rate of overall treatment. Nonapoptotic program cell death may assist to overcome worse clinical outcomes. Autophagy which is one of the nonapoptotic pathways provides another option for bladder cancer patients. Autophagy is reported as a potent anticancer therapy in some cancers. First of all, we established a mouse orthotopic bladder tumor formation model in order to create a similar tumor microenvironment. IVIS system and micro-ultrasound were utilized to noninvasively monitor tumor formation. In addition, we carried out intravesical treatment in our animal model to be consistent with human clinical treatment. In our study, we carried out intravesical instillation of the autophagy inducer in mouse orthotopic bladder tumor to observe tumor formation by noninvasive IVIS system and micro-ultrasound. Our results showed that bladder tumor formation is suppressed by the autophagy inducer, and there are no significant side effects in the physiology of mice. Furthermore, the autophagy inducer upregulated autophagy in bladder tissues of the treated mice was confirmed by Western blot, immunohistochemistry, and immunofluorescence. In conclusion, we reveal that a novel autophagy inducer with low side effects suppresses bladder tumor formation in our mouse orthotopic bladder tumor model, and it provides another therapeutic approach in bladder cancer patients.

Keywords: bladder cancer, transitional cell carcinoma, orthotopic bladder tumor formation model, autophagy

Procedia PDF Downloads 176

Authors: Naim Izet Kajtazi

Abstract:

Context: Although rare, glomus tumor (i.e., nonchromaffin chemodectomas and paragan¬gliomas) is the most common middle ear tumor, with female predominance. Pre-operative embolization is often required to devascularize the hypervascular tumor for better surgical outcomes. Process: A 35-year-old female presented with episodes of frequent dizziness, ear fullness, and right ear tinnitus for 12 months. Head imaging revealed a right glomus tympanicum tumor. She underwent pre-operative endovascular embolization of the glomus tympanicum tumor with surgical, cyanoacrylate-based glue. Immediately after the procedure, she developed drowsiness and severe pain in the right temporal region. Further investigations revealed a right cerebellar stroke in the posterior inferior cerebellar artery territory. She was treated with intravenous heparin, followed by one year of oral anticoagulation. With rehabilitation, she significantly recovered from her post embolization stroke. However, the tumor was resected at another institution. Ten years later, follow-up imaging indicated a gradual increase in the size of the glomus jugulare tumor, compressing the nearby critical vascular structures. She subsequently received radiation therapy to treat the residual tumor. Outcome: Currently, she has no neurological deficit, but her mild dizziness, right ear tinnitus, and hearing impairment persist. Relevance: This case highlights the complex nature of these tumors, which often bring challenges to the patients as well as treatment teams. The multi-disciplinary team approach is necessary to tailor the management plan for individual tumors. Although embolization is a safe procedure, careful attention and thoughtful anatomic knowledge regarding dangerous anastomosis are essential to avoid devastating complications. Complications occur due to encountered vessel anomalies and new anastomoses formed during the gluing and changes in hemodynamics.

Keywords: stroke, embolization, MRI brain, cerebral angiogram

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Authors: Fathi Kallel, Abdulelah Alabd Uljabbar, Abdulrahman Aldukhail, Abdulaziz Alomran

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The brain is an important organ in our body since it is responsible about the majority actions such as vision, memory, etc. However, different diseases such as Alzheimer and tumors could affect the brain and conduct to a partial or full disorder. Regular diagnosis are necessary as a preventive measure and could help doctors to early detect a possible trouble and therefore taking the appropriate treatment, especially in the case of brain tumors. Different imaging modalities are proposed for diagnosis of brain tumor. The powerful and most used modality is the Magnetic Resonance Imaging (MRI). MRI images are analyzed by doctor in order to locate eventual tumor in the brain and describe the appropriate and needed treatment. Diverse image processing methods are also proposed for helping doctors in identifying and analyzing the tumor. In fact, a large Computer Aided Diagnostic (CAD) tools including developed image processing algorithms are proposed and exploited by doctors as a second opinion to analyze and identify the brain tumors. In this paper, we proposed a new advanced CAD for brain tumor identification, classification and feature extraction. Our proposed CAD includes three main parts. Firstly, we load the brain MRI. Secondly, a robust technique for brain tumor extraction is proposed. This technique is based on both Discrete Wavelet Transform (DWT) and Principal Component Analysis (PCA). DWT is characterized by its multiresolution analytic property, that’s why it was applied on MRI images with different decomposition levels for feature extraction. Nevertheless, this technique suffers from a main drawback since it necessitates a huge storage and is computationally expensive. To decrease the dimensions of the feature vector and the computing time, PCA technique is considered. In the last stage, according to different extracted features, the brain tumor is classified into either benign or malignant tumor using Support Vector Machine (SVM) algorithm. A CAD tool for brain tumor detection and classification, including all above-mentioned stages, is designed and developed using MATLAB guide user interface.

Keywords: MRI, brain tumor, CAD, feature extraction, DWT, PCA, classification, SVM

Procedia PDF Downloads 249

Authors: Salvador Garcia Bernal, Chi Zheng, Keqi Zhang, Lei Mao

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Circulating Tumor Cells (CTC) is used to detect tumoral cell metastases using blood samples of patients with cancer (lung, breast, etc.). Using an immunofluorescent method a three channel image (Red, Green, and Blue) are obtained. These set of images usually overpass the 11 x 30 M pixels in size. An aided tool is designed for imaging cell analysis to segmented and identify the tumorous cell based on the three markers signals. Our Method, it is cell-based (area and cell shape) considering each channel information and extracting and making decisions if it is a valid CTC. The system also gives information about number and size of tumor cells found in the sample. We present results in real-life samples achieving acceptable performance in identifying CTCs in short time.

Keywords: Circulating Tumor Cells (CTC), cell analysis, immunofluorescent, medical image analysis

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Authors: Eddy K. Mukadi

Abstract:

This work is a documentary and descriptive study devoted to the epidemiological, clinical, histopathological and therapeutic profile of breast cancer deals with the department of gynecology and obstetrics of the university clinics of Kinshasa during the period from 1 January 2014 to 31 December 2014. We have identified 56 cases of breast cancer. These cancers accounted for 45.2% of gynecological mammary cancers. The youngest in our series was 18 years old while the oldest was 74 years old; And the mean age of these patients was 43.4 years and mostly multiparous (35.7%). Brides (60.7%) and bachelors (26.8%) were the most affected by breast cancer. The reasons for consultation were dominated by nodules in the breast (48.2%) followed by pain (35.7%) and nipple discharge (14.3%). In 89.2% of the cases, it was the advanced clinical stage (stage 3 and 4) and the infiltrating ductal carcinoma was the most frequent histological type (75%) The malignant tumor was mainly in the left breast (55.3%), and chemotherapy with hormone therapy and patey was the most convenient treatment (42.8%), while patey mastectomy was performed in 12.5% of patients. Because of the high incidence of breast cancer identified in our study, some preventive measures must be taken into account to address this public health problem, including breast autopalpation once a month, Early detection system development of a national breast cancer policy and the implementation of a national breast cancer control program.

Keywords: breast cancer, histopathological profile, epidemiological profile, Kinshasa

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Authors: Maria Valeria De Bonis, Gianpaolo Ruocco

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Nowadays, computational modeling is paving new design and verification ways in a number of industrial sectors. The technology is ripe to challenge some case in the Bioengineering and Medicine frameworks: for example, looking at the strategical and ethical importance of oncology research, efforts should be made to yield new and powerful resources to tumor knowledge and understanding. With these driving motivations, we approach this gigantic problem by using some standard engineering tools such as the mathematics behind the biomass transfer. We present here some bacterial colonization studies in complex structures. As strong analogies hold with some tumor proliferation, we extend our study to a benchmark case of solid tumor. By means of a commercial software, we model biomass and energy evolution in arbitrary media. The approach will be useful to cast virtualization cases of cancer growth in human organs, while augmented reality tools will be used to yield for a realistic aid to informed decision in treatment and surgery.

Keywords: bacteria, simulation, tumor, precision medicine

Procedia PDF Downloads 335

Authors: Roberto Coppo, Francesca Orso, Daniela Dettori, Elena Quaglino, Lei Nie, Mehran M. Sadeghi, Daniela Taverna

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Malignant melanoma is currently the fifth most common cancer in the white population and it is fatal in its metastatic stage. Several research studies in recent years have provided evidence that cancer initiation and progression are driven by genetic alterations of the tumor and paracrine interactions between tumor and microenvironment. Scattered data show that the Endothelial and Smooth muscle cell-Derived Neuropilin-like molecule (ESDN) controls cell proliferation and movement of stroma and tumor cells. To investigate the role of ESDN in the tumor microenvironment during melanoma progression, murine melanoma cells (B16 or B16-F10) were injected in ESDN knockout mice in order to evaluate how the absence of ESDN in stromal cells could influence melanoma progression. While no effect was found on primary tumor growth, increased cell extravasation and lung metastasis formation was observed in ESDN knockout mice compared to wild type controls. In order to understand how cancer cells cross the endothelial barrier during metastatic dissemination in an ESDN-null microenvironment, structure, and permeability of lung blood vessels were analyzed. Interestingly, ESDN knockout mice showed structurally altered and more permeable vessels compared to wild type animals. Since cell surface molecules mediate the process of tumor cell extravasation, the expression of a panel of extravasation-related ligands and receptors was analyzed. Importantly, modulations of N-cadherin, E-selectin, ICAM-1 and VAP-1 were observed in ESDN knockout endothelial cells, suggesting the presence of a favorable tumor microenvironment which facilitates melanoma cell extravasation and metastasis formation in the absence of ESDN. Furthermore, a potential contribution of immune cells in tumor dissemination was investigated. An increased recruitment of macrophages in the lungs of ESDN knockout mice carrying subcutaneous B16-F10 tumors was found. In conclusion, our data suggest a functional role of ESDN in the tumor microenvironment during melanoma progression and the identification of the mechanisms that regulate tumor cell extravasation could lead to the development of new therapies to reduce metastasis formation.

Keywords: melanoma, tumor microenvironment, extravasation, cell surface molecules

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Authors: Mahmoodreza Tahamtan

Abstract:

Background: Malignant surface epithelial ovarian tumors (SEOT) account for approximately 90% of primary ovarian cancer. Wilms tumor gene (WT1) product was defined as a tumor suppressor gene, but today it is considered capable of performing oncogenic functions. There seems to be differences in WT1 expression patterns among SEOT subtypes. We evaluate the immunohistochemical expression of WT1 protein among different histologic subtypes of SEOT. Materials and Methods: Immunohistochemistry for WT1 was done on 35 serous cystadenocarcinomas, 9 borderline serous tumors, 3 mucinous cystadenocarcinomas, 10 borderline mucinous tumors, 7 endometrioid ovarian carcinomas, 3 clear cell carcinomas, 1 malignant Brenner tumor, 2 metastatic adenocarcinomas, and 6 endometrial adenocarcinomas. 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%. Results: 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. All the mucinous tumors(n:13), endometrioid carcinomas (n: 7), clear cell carcinomas (n: 3), metastatic adenocarcinomas (n: 2) and primary endometrial carcinomas (n:6) were negative. The single malignant Brenner tumor showed a positive reaction for WT1(4+) Conclusion: WT1 is a good marker to distinguish primary ovarian serous carcinomas from other surface epithelial tumors (especially endometrioid subtype) and metastatic carcinomas (especially endometrial serous carcinoma), other than malignant mesothelioma. We cannot rely to the degree of expression inorder to separate high grade borderline serous tumors from low grade ones.

Keywords: WT1, ovary, epithelial tumors, malignant

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Authors: Rasime Kalkan, Emine Ikbal Atli, Ali Arslantaş, Muhsin Özdemir, Sevilhan Artan

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Glioblastoma (WHO grade IV), is the malignant form of brain tumor, the genetic background of the GBM is highly variable. The tumor mass of a GBM is multilayered and every tumor layer shows distinct characteristics with a different cell population. The treatment planning of GBM should be focused on the tumor genetic characteristics. We screened primary glioblastoma multiforme (GBM) in a population-based study for MGMT and RARβ methylation and IDH1 mutation correlated them with clinical data and treatment. There was no correlation between MGMT-promoter methylation and overall survival. The overall survival time of the patients with methylated RARβ was statically (OS;p<0,05) significance between the patients who were treated with chemotherapy and radiotherapy. Here we showed the status of IDH1 gene associatied with younger age. We demonstrated that the together with MGMT gene the RARβ gene should be used as a potantial treatment decision marker for GBMs.

Keywords: RARβ, primary glioblastoma multiforme, methylation, MGMT

Procedia PDF Downloads 344

Authors: Hatem A. El-Mezayen, Ahmed Abdelmajeed, Fatehya Metwally, Usama Elsaly, Salwa Atef

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Tumor metastasis involves the dissemination of malignant cells into the basement membrane and vascular system contributes to the circulating pool of these markers. In this context our aim has been focused on development of a non-invasive. Circulating tumor cells (CTCs) represent a unique liquid biopsy carrying comprehensive biological information of the primary tumor. Herein, we sought to develop a novel score based on the combination of the most significant CTCs biomarkers with and routine laboratory tests for accurate detection of metastatic breast cancer. Methods: Cytokeratin 18 (CK18), Cytokeratin 19 (CK19), and CA15.3 were assayed in metastatic breast cancer (MBC) patients (75), non-MBC patients (50) and healthy control (20). Results: Areas under receiving operating curve (AUCs) were calculated and used for construction on novel score. A novel score named MBC-CTCs = CA15.3 (U/L) × 0.08 + CK 18 % × 2.9 + CK19 × 3.1– 510. That function correctly classified 87% of metastatic breast cancer at cut-off value = 0.55. (i.e great than 0.55 indicates patients with metastatic breast cancer and less than 0.55 indicates patients with non-metastatic breast cancer). Conclusion: MBC-CTCs is a novel, non-invasive and simple can applied to discriminate patients with metastatic breast cancer.

Keywords: metastatic breast cancer, circulating tumor cells, cytokeratin, EpiCam

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Authors: Sudson Sirivaidyapong, Ratthanan Sathienbumrungkit, Nongnapas Ruangpet, Nattanun Uaprayoon, Chawisa Wejjakul

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Many factors initiate mammary gland tumor in female dogs such as age, breed, sex, estrous cycle, birth control and pseudopregnancy. Those factors are mostly associated with canine sex hormone. In this study, questionnaires and direct interviews were used to collect information from owners of female dogs that had been diagnosed as mammary tumors at our veterinary teaching hospital, during January 2015 to October 2016 to compare the prevalence of mammary tumor between nulliparous and multiparous female dogs. 200 dogs (from all 212 mammary tumor patients, some were excluded because of inadequate information) were included in the study, 72.5% were nulliparous and 27.5% were multiparous. The results revealed that breed, age, birth control age and birth control methods were not different in both groups; most dogs in both groups were various purebreds, geriatric age, and low incidence of hormonal contraception while 100% of multiparous dogs and 83.7% of nulliparous dogs had been neutered at over two years old. The significant differences between two groups were the frequency of pseudopregnancy and estrus which were much higher in nulliparous female dogs. It can be concluded from our study that nulliparous dogs may be more likely at higher risk of mammary tumor compared to multiparous dogs from various factors especially, the frequency of estrus and the occurrence of pseudopregnancy which related to more times of sex hormonal contact. This study was a preliminary data for further studies to determine the other risk factors of mammary gland tumors in dogs, and to our knowledge, it is the first report on a significantly higher prevalence of mammary tumor in nulliparous female dogs than that in multiparous dogs. This finding corresponds with the study of breast cancer in women but may be from different causes and factors due to the differences in estrous physiology.

Keywords: canine, female dogs, nulliparous, multiparous, mammary tumor, prevalence

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Authors: Tanveer Beg, Yasir H. Siddique, Gulshan Ara, Asfar S. Azmi, Mohammad Afzal

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Doxorubicin is a well-known DNA intercalating chemotherapy drug that is widely used for treatment of different cancers. Its clinical utility is limited due to the observed genotoxic side effects on healthy cells suggesting that newer combination and genoprotective regimens are urgently needed for the management of doxorubicin chemotherapy. Some dietary phytochemicals are well known for their protective mechanism of action and genistein from soy is recognized as an anti-oxidant with similar properties. Therefore, the present study investigates the effect of genistein against the genotoxic doses of doxorubicin by assessing chromosomal aberrations, sister chromatid exchanges, cell cycle kinetics, cell viability, apoptosis, and DNA damage markers in cultured human lymphocytes. Our results reveal that genistein treatment significantly suppresses genotoxic damage induced by doxorubicin. It is concluded that genistein has the potential to reduce the genotoxicity induced by anti-cancer drugs, thereby reducing the chances of developing secondary tumors during the therapy.

Keywords: apoptosis, DNA damage markers, doxorubicin, genistein, genotoxicity, human lymphocyte culture

Procedia PDF Downloads 359

Authors: Tianjiao Chu, Carla Rios Luci, Christy Maksoudian, Ara Sargsian, Bella B. Manshian, Stefaan J. Soenen

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Nanomaterials have gained high interest in their use as potent anticancer agents. Apart from delivering chemotherapeutic agents in order to reduce off-target effects, molecular agents have also been widely explored. The advances in our understanding of cell biology and cell death mechanisms1 has generated a broad library of potential therapeutic targets by siRNA, mRNA, or pDNA complexes. In the present study, we explore the ability of pDNA-polyplexes to induce tumor-specific necroptosis. This results in a cascade of effects, where immunogenic cell death potentiates anti-tumor immune responses and results in an influx of dendritic cells and cytotoxic T cells, rendering the tumor more amenable to immune checkpoint inhibition. This study aims to explore whether the induction of necroptosis in a subpopulation of tumor cells can be used to potentiate immune checkpoint inhibition studies.

Keywords: nanoparticle, MLKL, necroptosis, immunotherapy

Procedia PDF Downloads 139

Authors: Susanne Fridsten, Kristina Hellman, Anders Sundin, Lennart Blomqvist

Abstract:

Background: Patients diagnosed with locally advanced cervical carcinoma are treated with definitive concomitant chemo-radiotherapy. Treatment failure occurs in 30-50% of patients with very poor prognoses. The treatment is standardized with risk for both over-and undertreatment. Consequently, there is a great need for biomarkers able to predict therapy outcomes to allow for individualized treatment. Aim: To explore the role of T2- and diffusion-weighted magnetic resonance imaging (MRI) for early prediction of therapy outcome and the optimal time point for assessment. Methods: A pilot study including 15 patients with cervical carcinoma stage IIB-IIIB (FIGO 2009) undergoing definitive chemoradiotherapy. All patients underwent MRI four times, at baseline, 3 weeks, 5 weeks, and 12 weeks after treatment started. Tumour size, size change (∆size), visibility on diffusion-weighted imaging (DWI), apparent diffusion coefficient (ADC) and change of ADC (∆ADC) at the different time points were recorded. Results: 7/15 patients relapsed during the study period, referred to as "poor prognosis", PP, and the remaining eight patients are referred to "good prognosis", GP. The tumor size was larger at all time points for PP than for GP. The ∆size between any of the four-time points was the same for PP and GP patients. The sensitivity and specificity to predict prognostic group depending on a remaining tumor on DWI were highest at 5 weeks and 83% (5/6) and 63% (5/8), respectively. The combination of tumor size at baseline and remaining tumor on DWI at 5 weeks in ROC analysis reached an area under the curve (AUC) of 0.83. After 12 weeks, no remaining tumor was seen on DWI among patients with GP, as opposed to 2/7 PP patients. Adding ADC to the tumor size measurements did not improve the predictive value at any time point. Conclusion: A large tumor at baseline MRI combined with a remaining tumor on DWI at 5 weeks predicted a poor prognosis.

Keywords: chemoradiotherapy, diffusion-weighted imaging, magnetic resonance imaging, uterine cervical carcinoma

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Authors: Mary-Ann N. Jallad, Dalal F. Jaber, Alexander M. Abdelnoor

Abstract:

Introduction: Current evidence confirms that both innate and adaptive immune systems are capable of recognizing and abolishing malignant cells. The emergence of cancerous tumors in patients is, therefore, an indication that certain cancer cells can resist elimination by the immune system through a process known as “immune evasion”. In fact, cancer cells often exploit regulatory mechanisms to escape immunity. Such mechanisms normally exist to control the immune responses and prohibit exaggerated or autoimmune reactions. Recently, immunotherapies have shown promising yet limited results. Therefore this study investigates several immunotherapeutic combinations and devises a triple immunotherapy which harnesses the innate and acquired immune responses towards the annihilation of malignant cells through overcoming their ability of immune evasion, consequently hampering malignant progression and eliminating established tumors. The aims of the study are to rule out acute/chronic toxic effects of the proposed treatment combinations, to assess the effect of these combinations on tumor growth and survival rates, and to investigate potential mechanisms underlying the phenotypic results through analyzing serum levels of anti-tumor cytokines, angiogenic factors and tumor progression indicator, and the tumor-infiltrating immune-cells populations. Methodology: For toxicity analysis, cancer-free C57BL/6 mice are randomized into 9 groups: Group 1 untreated, group 2 treated with sterile saline (solvent of used treatments), group 3 treated with Monophosphoryl-lipid-A, group 4 with anti-CTLA4-antibodies, group 5 with 1-Methyl-Tryptophan (Indolamine-Dioxygenase-1 inhibitor), group 6 with both MPLA and anti-CTLA4-antibodies, group 7 with both MPLA and 1-MT, group 8 with both anti-CTLA4-antibodies and 1-MT, and group 9 with all three: MPLA, anti-CTLA4-antibodies and 1-MT. Mice are monitored throughout the treatment period and for three following months. At that point, histological sections from their main organs are assessed. For tumor progression and survival analysis, a murine melanoma model is generated by injecting analogous mice with B16F10 melanoma cells. These mice are segregated into the listed nine groups. Their tumor size and survival are monitored. For a depiction of underlying mechanisms, melanoma-bearing mice from each group are sacrificed at several time-points. Sera are tested to assess the levels of Interleukin-12 (IL-12), Vascular-Endothelial-Growth Factor (VEGF), and S100B. Furthermore, tumors are excised for analysis of infiltrated immune cell populations including T-cells, macrophages, natural killer cells and immune-regulatory cells. Results: Toxicity analysis shows that all treated groups present no signs of neither acute nor chronic toxicity. Their appearance and weights were comparable to those of control groups throughout the treatment period and for the following 3 months. Moreover, histological sections from their hearts, kidneys, lungs, and livers were normal. Work is ongoing for completion of the remaining study aims. Conclusion: Toxicity was the major concern for the success of the proposed comprehensive combinational therapy. Data generated so far ruled out any acute or chronic toxic effects. Consequently, ongoing work is quite promising and may significantly contribute to the development of more effective immunotherapeutic strategies for the treatment of cancer patients.

Keywords: cancer immunotherapy, check-point blockade, combination therapy, melanoma

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Authors: Vitor Rafael Regiani, Carlos Henrique Viesi Do Nascimento Filho, Patricia Matos Biselli-Chicote, Claudia Aparecida Rainho, Luiz Sergio Raposo, José Victor Maniglia, Eny Maria Goloni-Bertollo, Erika Cristina Pavarino

Abstract:

Promoter hypermethylation of tumor-related genes has been associated with prognosis in early-stage head-and-neck cancers, providing strong evidence that these hypermethylated genes are valuable biomarkers for prognostic evaluation. Hence, we selected the MGMT and RASSF1A genes to examine the methylation status in head and neck squamous cell carcinomas (HNSCC) samples matched with non-tumor tissues (tumor-surrounding tissues or peripheral blood samples). DNA methylation analysis was based on Methylation-Sensitive High Resolution Melting, and the methylation status was correlated with clinic-pathological characteristics of the patients. RASSF1A and MGMT promoter methylation was detected in 43.24% (16/37) and in 44.44% (16/36) of the tumors, respectively. RASSF1A and MGMT methylation was significantly more frequent in tumor tissue than non-tumor tissues, as well as, simultaneous methylation of RASSF1A and MGMT also was higher in tumor tissue than non-tumor tissues. In relation to anatomic site, larynx cancer presented significant methylation of MGMT gene compared to tumor-surrounding tissue. The frequency of RASSF1A and MGMT promoter methylated was higher in tumor tissues in relation to peripheral blood from the same patient. No association was found between methylation and the variables analyzed, including gender, age, smoking or alcohol drinking habits. Clinic-pathological characteristics also showed no association in the presence of methylation. The Kaplan–Meier's method showed no association of methylation and both disease-free and overall survival. In conclusion, the presence of epigenetic abnormalities in normal-appearing tissue corroborates the hypothesis of the ‘field cancerization', or it can reflect preneoplastic and/or preinvasive. Moreover, MGMT methylation may serve as an important laryngeal cancer biomarker because it showed significant difference between laryngeal cancer and surrounding tumor tissues.

Keywords: head and neck cancer, DNA methylation, MGMT promoter methylation, RASSF1A promoter methylation

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Authors: Thieu-Thi Tra My

Abstract:

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: Helen Dilman, Eyal Oz, Shmuel Hayun, Nahum Frage

Abstract:

The conventional approach for manufacturing silicon carbide and boron carbide reaction bonded composites is based on infiltrating a ceramic porous preform with molten silicon. The relatively high melting temperature of the silicon infiltrating medium is a drawback of the process. The present contribution is concerned with an approach that allows obtaining reaction bonded composites by pressure-less infiltration at a significantly lower (850-1000oC) temperature range. This approach was applied for the fabrication of fully dense SiC/(Si-Al) and (SiC+B4C)/(Si-Al) composites. The key feature of the approach is based on using Si alloys with low melting temperature and the Mg-vapor atmosphere, under which an adequate wetting between ceramics and liquid alloys for the infiltration process is achieved. In the first set of the experiments ceramic performs compacted from multimodal SiC powders (with the green density of about 27 vol. %) without free carbon addition were infiltrated by Si-20%Al alloy at 950oC. In the second set, 19 vol. % of a fine boron carbide powder was added to SiC powders as a source of carbon. The green density of the SiC-B4C preforms was about 23-25 vol. %. In both cases, successful infiltration was achieved and the composites were fully dense. The density of the composites was about 3g/cm3. For the SiC based composites the hardness value was 750±150HV, Young modulus-280GPa and bending strength-240±30MPa. These values for (SiC-B4C)/(Si-Al) composites (1460±200HV, 317GPa and 360±20MPa) were significantly higher due to the formation of novel ceramics phases. Microstructural characteristics of the composites and their phase composition will be discussed.

Keywords: boron carbide, composites, infiltration, low temperatures, silicon carbide

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Authors: Muhammad Hassan Khalil, Xu Jiadong

Abstract:

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

Abstract:

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

Abstract:

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

Procedia PDF Downloads 482