Search results for: cancerous tumor

Authors: Pamela R. Jackson, Andrea Hawkins-Daarud, Cassandra R. Rickertsen, Kamala Clark-Swanson, Scott A. Whitmire, Kristin R. Swanson

Abstract:

Glioblastoma Multiforme (GBM), the most common primary brain tumor, often presents with hyperintensity on T2-weighted or T2-weighted fluid attenuated inversion recovery (T2/FLAIR) magnetic resonance imaging (MRI). This hyperintensity corresponds with vasogenic edema, however there are likely many infiltrating tumor cells within the hyperintensity as well. While MRIs do not directly indicate tumor cells, MRIs do reflect the microenvironmental water abnormalities caused by the presence of tumor cells and edema. The inherent heterogeneity and resulting MRI features of GBMs complicate assessing disease response. To understand how hyperintensity on T2/FLAIR MRI may correlate with edema in the extracellular space (ECS), a multi-compartmental MRI signal equation which takes into account tissue compartments and their associated volumes with input coming from a mathematical model of glioma growth that incorporates edema formation was explored. The reasonableness of two possible extracellular space schema was evaluated by varying the T2 of the edema compartment and calculating the possible resulting T2s in tumor and peripheral edema. In the mathematical model, gliomas were comprised of vasculature and three tumor cellular phenotypes: normoxic, hypoxic, and necrotic. Edema was characterized as fluid leaking from abnormal tumor vessels. Spatial maps of tumor cell density and edema for virtual tumors were simulated with different rates of proliferation and invasion and various ECS expansion schemes. These spatial maps were then passed into a multi-compartmental MRI signal model for generating simulated T2/FLAIR MR images. Individual compartments’ T2 values in the signal equation were either from literature or estimated and the T2 for edema specifically was varied over a wide range (200 ms – 9200 ms). T2 maps were calculated from simulated images. T2 values based on simulated images were evaluated for regions of interest (ROIs) in normal appearing white matter, tumor, and peripheral edema. The ROI T2 values were compared to T2 values reported in literature. The expanding scheme of extracellular space is had T2 values similar to the literature calculated values. The static scheme of extracellular space had a much lower T2 values and no matter what T2 was associated with edema, the intensities did not come close to literature values. Expanding the extracellular space is necessary to achieve simulated edema intensities commiserate with acquired MRIs.

Keywords: extracellular space, glioblastoma multiforme, magnetic resonance imaging, mathematical modeling

Procedia PDF Downloads 209

Authors: Chih Jou Hsiao, Chung Ming Lo, Li Chun Hsieh

Abstract:

Brain tumor is not the cancer having high incidence rate, but its high mortality rate and poor prognosis still make it as a big concern. On clinical examination, the grading of brain tumors depends on pathological features. However, there are some weak points of histopathological analysis which can cause misgrading. For example, the interpretations can be various without a well-known definition. Furthermore, the heterogeneity of malignant tumors is a challenge to extract meaningful tissues under surgical biopsy. With the development of magnetic resonance imaging (MRI), tumor grading can be accomplished by a noninvasive procedure. To improve the diagnostic accuracy further, this study proposed a computer-aided diagnosis (CAD) system based on MRI features to provide suggestions of tumor grading. Gliomas are the most common type of malignant brain tumors (about 70%). This study collected 34 glioblastomas (GBMs) and 73 lower-grade gliomas (LGGs) from The Cancer Imaging Archive. After defining the region-of-interests in MRI images, multiple quantitative morphological features such as region perimeter, region area, compactness, the mean and standard deviation of the normalized radial length, and moment features were extracted from the tumors for classification. As results, two of five morphological features and three of four image moment features achieved p values of <0.001, and the remaining moment feature had p value <0.05. Performance of the CAD system using the combination of all features achieved the accuracy of 83.18% in classifying the gliomas into LGG and GBM. The sensitivity is 70.59% and the specificity is 89.04%. The proposed system can become a second viewer on clinical examinations for radiologists.

Keywords: brain tumor, computer-aided diagnosis, gliomas, magnetic resonance imaging

Procedia PDF Downloads 231

Authors: Shenlun Chen, Leonard Wee

Abstract:

Tumor grading is an essential reference for colorectal cancer (CRC) staging and survival prognostication. The widely used World Health Organization (WHO) grading system defines histological grade of CRC adenocarcinoma based on the density of glandular formation on whole slide images (WSI). Tumors are classified as well-, moderately-, poorly- or un-differentiated depending on the percentage of the tumor that is gland forming; >95%, 50-95%, 5-50% and <5%, respectively. However, manually grading WSIs is a time-consuming process and can cause observer error due to subjective judgment and unnoticed regions. Furthermore, pathologists’ grading is usually coarse while a finer and continuous differentiation grade may help to stratifying CRC patients better. In this study, a deep learning based automatic differentiation grading algorithm was developed and evaluated by survival analysis. Firstly, a gland segmentation model was developed for segmenting gland structures. Gland regions of WSIs were delineated and used for differentiation annotating. Tumor regions were annotated by experienced pathologists into high-, medium-, low-differentiation and normal tissue, which correspond to tumor with clear-, unclear-, no-gland structure and non-tumor, respectively. Then a differentiation prediction model was developed on these human annotations. Finally, all enrolled WSIs were processed by gland segmentation model and differentiation prediction model. The differentiation grade can be calculated by deep learning models’ prediction of tumor regions and tumor differentiation status according to WHO’s defines. If multiple WSIs were possessed by a patient, the highest differentiation grade was chosen. Additionally, the differentiation grade was normalized into scale between 0 to 1. The Cancer Genome Atlas, project COAD (TCGA-COAD) project was enrolled into this study. For the gland segmentation model, receiver operating characteristic (ROC) reached 0.981 and accuracy reached 0.932 in validation set. For the differentiation prediction model, ROC reached 0.983, 0.963, 0.963, 0.981 and accuracy reached 0.880, 0.923, 0.668, 0.881 for groups of low-, medium-, high-differentiation and normal tissue in validation set. Four hundred and one patients were selected after removing WSIs without gland regions and patients without follow up data. The concordance index reached to 0.609. Optimized cut off point of 51% was found by “Maxstat” method which was almost the same as WHO system’s cut off point of 50%. Both WHO system’s cut off point and optimized cut off point performed impressively in Kaplan-Meier curves and both p value of logrank test were below 0.005. In this study, gland structure of WSIs and differentiation status of tumor regions were proven to be predictable through deep leaning method. A finer and continuous differentiation grade can also be automatically calculated through above models. The differentiation grade was proven to stratify CAC patients well in survival analysis, whose optimized cut off point was almost the same as WHO tumor grading system. The tool of automatically calculating differentiation grade may show potential in field of therapy decision making and personalized treatment.

Keywords: colorectal cancer, differentiation, survival analysis, tumor grading

Procedia PDF Downloads 111

Authors: B. Shukir, L. Szivos, D. Kis, P. Barzo

Abstract:

Glioblastoma is the most malignant brain tumor. In general, the survival rate varies between (14-18) months. Glioblastoma consists a solid and infiltrative part. The standard therapeutic management of glioblastoma is maximum safe resection followed by chemo-radiotherapy. It’s hypothesized that the pretumoral hyperintense region in fluid attenuated inversion recovery (FLAIR) images includes both vasogenic edema and infiltrated tumor cells. In our study, we aimed to define the sensitivity and specificity of hyperintense FLAIR images preoperatively to examine how well it can define the true extent of glioblastoma. (16) glioblastoma patients included in this study. Hyperintense FLAIR region were delineated preoperatively as tumor mask. The infiltrative part of glioblastoma considered the regions where the tumor recurred on the follow up MRI. The recurrence on the CE-T1 images was marked as the recurrence masks. According to (AAL3) and (JHU white matter labels) atlas, the brain divided into cortical and subcortical regions respectively. For calculating specificity and sensitivity, the FLAIR and the recurrence masks overlapped counting how many regions affected by both . The average sensitivity and specificity was 83% and 85% respectively. Individually, the sensitivity and specificity varied between (31-100)%, and (100-58)% respectively. These results suggest that despite FLAIR being as an effective radiologic imaging tool its prognostic value remains controversial and probabilistic tractography remain more reliable available method for identifying the true extent of glioblastoma.

Keywords: brain tumors, glioblastoma, MRI, FLAIR

Procedia PDF Downloads 11

Authors: Harukuni Tokuda, Takanari Arai, Xu FengHao, Nobutaka Suzuki

Abstract:

In our continuous search for anti-tumor promoting, chemopreventive active potency from natural source material, a kind of healthy tea, Gromwell seed (Coix lachryma-jobi) ext., and including compounds Monoolein and Trilinolein have been screened using the in vitro synergistic assay indicated by inhibitory effects on the induction of Epstein-Barr virus early antigen (EBV-EA) by TPA. In assay, Gromwell seed aqueous extract and hot aqueous extract exhibited the potential inhibitory effects on EBV-EA activation without strong cytotoxicity on Raji cells. In our experimental system, the inhibitory effects of both Gromwell extracts and compounds were greater than that of beta-carotene, which is known anti-tumor promoting agent and/or chemopreventive agent. These compounds were evaluated for their in vitro inhibitory effect on EBV-EA activation induced by TPA. The percentages of the inhibition of TPA-induced EBV-EA activation for these materials were 60% and 30% at concentration 100 μg. Based on the results obtained in vitro, we studied the inhibitory effect of compounds, in an in vivo two-stage carcinogenesis test of mouse skin papilloma using DMBA as an initiator and TPA as a potential promoter. The control animals showed a 100% incidence of papilloma at 20 weeks after DMBA-TPA tumor promotion, while treatment with compounds reduced the percentage of number of tumor to 60 % after 20 weeks. Results from in vitro and in vivo studies showing chemopreventive activity against TPA promoting stage and these data support the effective potency of carcinogenic stage in clinical evaluation of integrative oncology.

Keywords: gromwell seed, medicinal plant, chemoprevention, pharmaceutical medicine

Procedia PDF Downloads 377

Authors: Cheng-Cao Sun, Shu-Jun Li, De-Jia Li

Abstract:

Determinants of growth and metastasis in cancer remain of great interest to define. MicroRNAs (miRNAs) have frequently emerged as tumor metastatic regulator by acting on multiple signaling pathways. Here, we report the definition of miR-346 as an oncogenic microRNA that facilitates non-small cell lung cancer (NSCLC) cell growth and metastasis. XPC, an important DNA damage recognition factor in nucleotide excision repair was defined as a target for down-regulation by miR-346, functioning through direct interaction with the 3'-UTR of XPC mRNA. Blocking miR-346 by an antagomiR was sufficient to inhibit NSCLC cell growth and metastasis, an effect that could be phenol-copied by RNAi-mediated silencing of XPC. In vivo studies established that miR-346 overexpression was sufficient to promote tumor growth by A549 cells in xenografts mice, relative to control cells. Overall, our results defined miR-346 as an oncogenic miRNA in NSCLC, the levels of which contributed to tumor growth and invasive aggressiveness.

Keywords: microRNA-346, miR-346, XPC, non-small cell lung cancer, oncogenesis

Procedia PDF Downloads 277

Authors: Gökçe Erdemir, İlhan Yaylım, Serap Erdem-Kuruca, Musa Mutlu Can

Abstract:

It has been determined that the main reason for the death of cancer disease is caused by metastases rather than the primary tumor. The cells that leave the primary tumor and enter the circulation and cause metastasis in the secondary organs are called "circulating tumor cells" (CTCs). The presence and number of circulating tumor cells has been associated with poor prognosis in many major types of cancer, including breast, prostate, and colorectal cancer. It is thought that knowledge of circulating tumor cells, which are seen as the main cause of cancer-related deaths due to metastasis, plays a key role in the diagnosis and treatment of cancer. The fact that tissue biopsies used in cancer diagnosis and follow-up are an invasive method and are insufficient in understanding the risk of metastasis and the progression of the disease have led to new searches. Liquid biopsy tests performed with a small amount of blood sample taken from the patient for the detection of CTCs are easy and reliable, as well as allowing more than one sample to be taken over time to follow the prognosis. However, since these cells are found in very small amounts in the blood, it is very difficult to capture them and specially designed analytical techniques and devices are required. Methods based on the biological and physical properties of the cells are used to capture these cells in the blood. Early diagnosis is very important in following the prognosis of tumors of epithelial origin such as breast, lung, colon and prostate. Molecules such as EpCAM, vimentin, and cytokeratins are expressed on the surface of cells that pass into the circulation from very few primary tumors and reach secondary organs from the circulation, and are used in the diagnosis of cancer in the early stage. For example, increased EpCAM expression in breast and prostate cancer has been associated with prognosis. These molecules can be determined in some blood or body fluids to be taken from patients. However, more sensitive methods are required to be able to determine when they are at a low level according to the course of the disease. The aim is to detect these molecules found in very few cancer cells with the help of sensitive, fast-sensing biosensors, first in breast cancer cells reproduced in vitro and then in blood samples taken from breast cancer patients. In this way, cancer cells can be diagnosed early and easily and effectively treated.

Keywords: electrochemical biosensors, breast cancer, circulating tumor cells, EpCAM, Vimentin, Cytokeratins

Procedia PDF Downloads 227

Authors: O. C. Abbah, O. Obidoa, J. Omale

Abstract:

Prostate tumor is fast becoming a leading cause of morbidity and mortality in human male adults, with 50 percent of men aged 50 years and above having histological evidence of the benign tumor. The study was set out to undertake phytochemical screening and proximate analysis of the pulp of A. muricata fruit - soursop; to determine the acute toxicity of the fruit pulp extract and its effect on male albino Wistar rats with concurrent induction of experimental benign prostate hyperplasia (BPH). Eighteen rats (average weight of 100g) were used for the lethality studies and were orally administered graded doses of aqueous extracts of the fruit pulp up to 5000 mg/kg body weight. Twenty five rats weighing 150-200g were divided into five groups of five rats each for the tumor studies. The groups included four controls – Hormone control, HC, which took Testosterone, T; and Estradiol, E2 – only, in olive oil as vehicle; Vehicle control, VC; Soursop control, SC, which received the extract only; VS, Vehicle and Soursop – and the Test group, TG (500mg/kg b.w.). All rats were dosed orally. Tumor was induced with exogenous Testosterone propionate: Estradiol valerate at 300µg: 80µg/kg b.w. (respectively) in olive oil, administered subcutaneously in the inguinal region of the rats on alternate days for 21 days. Administration of the fruit pulp at graded doses up to 5000mg/kg resulted in no lethality even after 72 hours. Results from tumor studies revealed that the administration of the fruit extracts significantly (p < 0.05) reduced the relative prostate weight of the TG compared with the HC, with values of 006±0.001 and 0.010±0.003 respectively. Treatment with vehicle, soursop and vehicle with soursop caused no significant (p>0.05) change in prostate size, with their respective relative prostate weights being 0.002±0.001, 0.004±0.002 and 0.002±0.001 compared with TG. Also, treatment with A. muricata fruit extract significantly decreased (p < 0.05) serum prostate specific antigen, PSA, in TG compared with HC, with values 0.055±0.017 and 0.194±0.068 ng/ml respectively. Furthermore, A. muricata administration displayed Testosterone boosting, Estradiol lowering and consequently testosterone-estradiol ratio increasing potential at the end of the 21 days. The preventive property of soursop against experimental BPH was corroborated by histological evidence in this study. The study concludes that A. muricata fruit holds a great potential for benign prostate tumor prevention and, possibly, management.

Keywords: annona muricata, benign prostate tumor, hormone, preventive potential, soursop

Procedia PDF Downloads 283

Authors: Soroosh Torabi, Brad Berron, Ren Xu, Christine Trinkle

Abstract:

Microfluidics integrated with 3D cell culture is a powerful technology to mimic cellular environment, and can be used to study cell activities such as proliferation, migration and response to drugs. This technology has gained more attention in cancer studies over the past years, and many organ-on-a-chip systems have been developed to study cancer cell behaviors in an ex-vivo tumor microenvironment. However, there are still some barriers to adoption which include low throughput, complexity in 3D cell culture integration and limitations on non-optical analysis of cells. In this study, a user-friendly microfluidic multi-well plate was developed to mimic the in vivo tumor microenvironment. The microfluidic platform feeds multiple 3D cell culture sites at the same time which enhances the throughput of the system. The platform uses hydrophobic Cassie-Baxter surfaces created by microchannels to enable convenient loading of hydrogel/cell suspensions into the device, while providing barrier free placement of the hydrogel and cells adjacent to the fluidic path. The microchannels support convective flow and diffusion of nutrients to the cells and a removable lid is used to enable further chemical and physiological analysis on the cells. Different breast cancer cell lines were cultured in the device and then monitored to characterize nutrient delivery to the cells as well as cell invasion and proliferation. In addition, the drug response of breast cancer cell lines cultured in the device was compared to the response in xenograft models to the same drugs to analyze relevance of this platform for use in future drug-response studies.

Keywords: microfluidics, multi-well 3d cell culture, tumor microenvironment, tumor-on-a-chip

Procedia PDF Downloads 235

Authors: Yuxiang Pan, Yong Qiu, Chenlei Gu, Ping Wang

Abstract:

In the past decade, three-dimensional (3D) tumor cell models have attracted increasing interest in the field of drug screening due to their great advantages in simulating more accurately the heterogeneous tumor behavior in vivo. Drug sensitivity testing based on 3D tumor cell models can provide more reliable in vivo efficacy prediction. The gold standard fluorescence staining is hard to achieve the real-time and label-free monitoring of the viability of 3D tumor cell models. In this study, micro-groove impedance sensor (MGIS) was specially developed for dynamic and non-invasive monitoring of 3D cell viability. 3D tumor cells were trapped in the micro-grooves with opposite gold electrodes for the in-situ impedance measurement. The change of live cell number would cause inversely proportional change to the impedance magnitude of the entire cell/matrigel to construct and reflect the proliferation and apoptosis of 3D cells. It was confirmed that 3D cell viability detected by the MGIS platform is highly consistent with the standard live/dead staining. Furthermore, the accuracy of MGIS platform was demonstrated quantitatively using 3D lung cancer model and sophisticated drug sensitivity testing. In addition, the parameters of micro-groove impedance chip processing and measurement experiments were optimized in details. The results demonstrated that the MGIS and 3D cell-based biosensor and would be a promising platform to improve the efficiency and accuracy of cell-based anti-cancer drug screening in vitro.

Keywords: micro-groove impedance sensor, 3D cell-based biosensors, 3D cell viability, micro-electromechanical systems

Procedia PDF Downloads 107

Authors: Priyanka Chowdhury, Asitikantha Sarma, Utpal Ghosh

Abstract:

Hadron therapy using high Linear Energy Transfer (LET) ion beam is producing promising clinical results worldwide. The major advantages are its ability to kill radio-resistant tumor and its anti-metastatic activity. Poly(ADP-ribose) polymerase-1 (PARP-1) inhibitors have been widely used as radiosensitizer, but its role in metastasis is unknown. The purpose of our study was to investigate the effect of PARP-1 depletion in combination with either Carbon Ion Beam (CIB) or gamma irradiation on metastatic potential of cultured cancerous cells. A549 cells were irradiated with CIB (0-4Gy) or gamma (0, 2, 4, 6 and 10 Gy) with and without PARP-1 inhibition. The metastatic potential of the cells was determined by cell migratory assay, expression, and activity of MMP-2 and MMP-9, expression of Cadherin, Fibronectin, and Vimentin. CIB exposure reduced migratory property and activity of MMP-2 and MMP-9 significantly. CIB with PARP-1 inhibition reduced cell migration and Matrix Metalloproteinase (MMPs) activity in a synergistic manner. Expression of MMPs was also down-regulated in CIB and combined treatment. On the contrary, MMP- 2 and MMP-9 activity was significantly increased in gamma irradiated cells but decreased upon combined treatment of gamma and PARP-1 inhibitor. MMPs expression and migration was reduced when gamma irradiation was combined with PARP-1 inhibition. Thus, our study clearly demonstrates that PARP-1 inhibition in combination with either high or low LET can significantly suppress metastatic potential in cancer cells and thereby can be a promising tool in controlling metastatic cancers.

Keywords: high LET, low LET, matrix metalloproteinase (MMP), PARP-1

Procedia PDF Downloads 192

Authors: J. R. Ashrapov, G. A. Alihodzhaeva, D. E. Abdullaev, N. R. Kadirbekov

Abstract:

Diagnosis of brain tumors is one of the challenges, as several central nervous system diseases run the same symptoms. Modern diagnostic techniques such as CT, MRI helps to significantly improve the surgery in the operating period, after surgery, after allowing time to identify postoperative complications in neurosurgery. Purpose: To study the MRI characteristics and localization of brain tumors in children and to detect the postoperative complications in the postoperative period. Materials and methods: A retrospective study of treatment of 62 children with brain tumors in age from 2 to 5 years was performed. Results of the review: MRI scan of the brain of the 62 patients 52 (83.8%) case revealed a brain tumor. Distribution on MRI of brain tumors found in 15 (24.1%) - glioblastomas, 21 (33.8%) - astrocytomas, 7 (11.2%) - medulloblastomas, 9 (14.5%) - a tumor origin (craniopharyngiomas, chordoma of the skull base). MRI revealed the following characteristic features: an additional sign of the heterogeneous MRI signal of hyper and hypointensive T1 and T2 modes with a different perifocal swelling degree with involvement in the process of brain vessels. The main objectives of postoperative MRI study are the identification of early or late postoperative complications, evaluation of radical surgery, the identification of the extended-growing tumor that (in terms of 3-4 weeks). MRI performed in the following cases: 1. Suspicion of a hematoma (3 days or more) 2. Suspicion continued tumor growth (in terms of 3-4 weeks). Conclusions: Magnetic resonance tomography is a highly informative method of diagnostics of brain tumors in children. MRI also helps to determine the effectiveness and tactics of treatment and the follow up in the postoperative period.

Keywords: brain tumors, children, MRI, treatment

Procedia PDF Downloads 112

Authors: Wooseok Byon, Eunyoung Kim, Junseong Kwon, Byung Joo Song, Chan Heun Park

Abstract:

Background/Purpose: Previous preclinical and clinical data suggest that increased lymphocytic infiltration would be associated with good prognosis and benefit from immunogenic chemotherapy especially in triple-negative breast cancer (TNBC). We investigated a single-center experience of TNBC and relationship with lymphocytic infiltration. Methods: From January 2004 to December 2012, at the Department of Surgery, Kangbuk Samsung Hospital, Sungkyunkwan University, School of Medicine, we retrospectively reviewed 897 breast cancer patients-clinical outcomes, clinicopathological characteristics, breast cancer subtypes. And we reviewed lymphocytic infiltration of TNBC specimens by two pathologists. Statistical analysis of risk factors associated with recurrence was performed. Results: A total of 897 patients, 76 were TNBC (8.47%). Mean age of TNBC patients were 50.95 (SD10.42) years, mean follow-up periods was 40.06 months. We reviewed 49 slides, and there were 8 recurrent breast cancer patients (16.32%), and 4 patients were expired (8.16%). There were 9 lymphocytic predominant breast cancers (LPBC)-carcinomas with either intratumoral lymphocytes in >60% of tumor cell nests. 1 patient of LPBC was recurred and 8 were not. In multivariate logistic regression, the odds ratio of lymphocytic infiltration was 0.59 (p=0.643). Conclusion: In a single-center experience of TNBC, the lymphocytic infiltration in tumor cell nest might be a good trend on the prognosis but there was not statistically significant.

Keywords: tumor-infiltrating lymphocytes, triple negative breast cancer, medical and health sciences

Procedia PDF Downloads 384

Authors: D. Suman, M. Venkateshwara Rao

Abstract:

Cancer is a disease caused by an uncontrolled division of abnormal cells in a part of the body, which is affecting millions of people leading to death. Even though there have been tremendous developments taken place over the last few decades the effective therapy for cancer is still not a reality. The existing techniques of cancer therapy are chemotherapy and radio therapy which are having their limitations in terms of the side effects, patient discomfort, radiation hazards and the localization of treatment. This paper describes a novel method for cancer therapy by using RF-hyperthermia application of nanoparticles. We have synthesized ferromagnetic nanoparticles and characterized by using XRD and TEM. These nanoparticles after the biocompatibility studies will be injected in to the body with a suitable tracer element having affinity to the specific tumor site. When RF energy is applied to the nanoparticles at the tumor site it produces heat of excess room temperature and nearly 41-45°C is sufficient to kill the tumor cells. We have designed a RF source generator provided with a temperature feedback controller to control the radiation induced temperature of the tumor site. The temperature control is achieved through a negative feedback mechanism of the thermocouple and a relay connected to the power source of the RF generator. This method has advantages in terms of its effect like localized therapy, less radiation, and no side effects. It has several challenges in designing the RF source provided with coils suitable for the tumour site, biocompatibility of the nanomaterials, cooling system design for the RF coil. If we can overcome these challenges this method will be a huge benefit for the society.

Keywords: hyperthermia, cancer therapy, RF source generator, nanoparticles

Procedia PDF Downloads 438

Authors: Nouf A. Aldarmahi, Nesrin I. Tarbiah, Nuha A. Alkhattabi, Huda F. Alshaibi

Abstract:

Nigella sativa which is known as dark cumin is a well-known example for a widely applicable herbal medicine. Nigella sativa can be effective in a variety of diseases such as hypertension, diabetes, bronchitis, gastrointestinal upset, and cancer. The anticancer effect of Nigella sativa appeared to be mediated by immune-modulatory effect through stimulating human natural killer (NK) cells. This is a type of lymphocytes which is part of the innate immunity, also known as the first line of defense in the body against pathogens. This study investigated the effect of thymoquinone as a major component of Nigella sativa on the molecular cytotoxic pathway of NK cell and the role of thymoquinone therapeutic effect on NK cells. NK cells were cultured with breast tumor cells in different ways and cultured media was collected and the concentration of perforin, granzyme B and interferon-α were measured by ELISA. The cytotoxic effect of NK cells on breast tumor cells was enhanced in the presence of thymoquinone, with increased activity of perforin in NK cells. This improved anticancer effect of thymoquinone on breast cancer cells.

Keywords: breast cancer, cancer cells, natural killer cells, thymoquinone

Procedia PDF Downloads 211

Authors: Paul J Yazaki, Michael Bouvet, John Shively

Abstract:

Surgery for solid gastrointestinal (GI) cancers such as pancreatic, colorectal, and gastric adenocarcinoma remains the mainstay of curative therapy. Complete resection of the primary tumor with negative margins (R0 resection), its draining lymph nodes, and distant metastases offers the optimal surgical benefit. Real-time fluorescence guided surgery (FGS) promises to improve GI cancer outcomes and is rapidly advancing with tumor-specific antibody conjugated fluorophores that can be imaged using near infrared (NIR) technology. Carcinoembryonic Antigen (CEA) is a non-internalizing tumor antigen validated as a surface tumor marker expressed in >95% of colorectal, 80% of gastric, and 60% of pancreatic adenocarcinomas. Our humanized anti-CEA hT84.66-M5A (M5A) monoclonal antibody (mAb)was conjugated with the NHS-IRDye800CW fluorophore and shown it can rapidly and effectively NIRoptical imageorthotopically implanted human colon and pancreatic cancer in mouse models. A limitation observed is that these NIR-800 dye conjugated mAbs have a rapid clearance from the blood, leading to a narrow timeframe for FGS and requiring high doses for effective optical imaging. We developed a novel antibody-fluorophore conjugate by incorporating a PEGylated sidearm linker to shield or mask the IR800 dye’s hydrophobicity which effectively extended the agent’s blood circulation half-life leading to increased tumor sensitivity and lowered normal hepatic uptake. We hypothesized that our unique anti-CEA linked to the fluorophore, IR800 by PEGylated sidewinder, M5A-SW-IR800 will become the next generation optical imaging agent, safe, effective, and widely applicable for intraoperative image guided surgery in CEA expressing GI cancers.

Keywords: optical imaging, anti-CEA, cancer, fluorescence-guided surgery

Procedia PDF Downloads 117

Authors: Hossain A, Hossain S.

Abstract:

Introduction: In a small cohort, we sought to assess the magnetic resonance spectroscopy's (MRS) ability to predict the presence of metastatic lesions. Method: A Popular Diagnostic Centre Limited enrolled patients with neuroepithelial tumors. The 1H CSI MRS of the brain allows us to detect changes in the concentration of specific metabolites caused by metastatic lesions. Among these metabolites are N-acetyl-aspartate (NNA), creatine (Cr), and choline (Cho). For Cho, NAA, Cr, and Cr₂, the metabolic ratio was calculated using the division method. Results: The NAA values were 0.63 and 5.65 for tumor cells, 1.86 and 5.66 for normal cells, and 1.86 and 5.66 for normal cells 2. NAA values for normal cells 1 were 1.84, 10.6, and 1.86 for normal cells 2, respectively. Cho levels were as low as 0.8 and 10.53 in the tumor cell, compared to 1.12 and 2.7 in the normal cell 1 and 1.24 and 6.36 in the normal cell 2. Cho/Cr₂ barely distinguished itself from the other ratios in terms of significance. For tumor cells, the ratios of Cho/NAA, Cho/Cr₂, NAA/Cho, and NAA/Cr₂ were significant. Normal cell 1 had significant Cho/NAA, Cho/Cr, NAA/Cho, and NAA/Cr ratios. Conclusion: The clinical result can be improved by using 1H-MRSI to guide the size of resection for metastatic lesions. Even though it is non-invasive and doesn't present any difficulties during the procedure, MRS has been shown to predict the detection of metastatic lesions.

Keywords: metabolite ratio, MRI images, metastatic lesion, MR spectroscopy, N-acetyl-aspartate

Procedia PDF Downloads 70

Authors: H. M. Abdelmoneim, N. A. Babtain, A. S. Barhamain, A. Z. Kufiah, A. S. Malibari, S. F. Munassar, R. S. Rawa

Abstract:

Introduction: Prostate cancer is one of the most common causes of morbidity and mortality in men in developed countries. Cancer Stem Cells (CSCs) could be responsible for the progression and relapse of cancer. Therefore, CSCs markers could provide a prognostic strategy for human malignancies. Aldehyde dehydrogenase 1A1 (ALDH1A1) activity has been shown to be associated with tumorigenesis and proposed to represent a functional marker for tumor initiating cells in various tumor types including prostate cancer. Material & Methods: We analyzed the immunohistochemical expression of ALDH1A1 in benign prostatic hyperplasia (BPH), prostatic intraepithelial neoplasia (PIN) and prostatic adenocarcinoma and assessed their significant correlations in 50 TURP sections. They were microscopically interpreted and the results were correlated with histopathological types and tumor grade. Results: In different prostatic histopathological lesions we found that ALDH1A1 expression was low in BPH (13.3%) and PIN (6.7%) and then its expression increased with prostatic adenocarcinoma (40%), and this was statistically highly significant (P value = 0.02). However, in different grades of prostatic adenocarcinoma we found that the higher the Gleason grade the higher the expression for ALDH1A1 and this was statistically significant (P value = 0.02). We compared the expression of ALDH1A1 in PIN and prostatic adenocarcinoma. ALDH1A1 expression was decreased in PIN and highly expressed in prostatic adenocarcinoma and this was statistically significant (P value = 0.04). Conclusion: Increasing ALDH1A1 expression is correlated with aggressive behavior of the tumor. Immunohistochemical expression of ALDH1A1 might provide a potential approach to study tumorigenesis and progression of primary prostate carcinoma.

Keywords: ALDH1A1, BPH, PIN, prostatic adenocarcinoma

Procedia PDF Downloads 235

Authors: M. Mousavi-Daramoroudi, H. Yousefnia, F. Abbasi-Davani, S. Zolghadri, S. Kakaei

Abstract:

Despite the appropriate characteristics of ¹⁷⁷Lu and DOTATOC, to our best knowledge, the therapeutic benefit of ¹⁷⁷Lu-DOTATOC complex in breast cancer has not been reported until now. In this study, biodistribution of ¹⁷⁷Lu-DOTA-TOC in mouse tumor model for evaluation of possible utilization of this complex in breast cancer treatment was investigated.¹⁷⁷Lu was prepared with the specific activity of 2.6-3 GBq.mg^-1 and radionuclidic purity higher than 99%. The radiolabeled complex was prepared in the optimized conditions with the radiochemical purity higher than 99%. The final solution was injected to the BALB/c mice with adenocarcinoma breast cancer. The biodistribution results showed major accumulation in the kidneys as the major excretion route and the somatostatin receptor-positive tissues such as pancreas compared with the other tissues. Also, significant uptake was observed in tumor even in longer time after injection. According to the results obtained in this research study, somatostatin receptors expressed in breast cancers can be targeted with DOTATOC analogues especially with ¹⁷⁷Lu-DOTATOC as an ideal therapeutic agent.

Keywords: ¹⁷⁷Lu, adenocarcinoma breast cancer, DOTATOC, BALB/c mice

Procedia PDF Downloads 196

Authors: Mohammad Ali Oghabian, Reza Reiazi, Esmaeel Parsai, Mehdi Aghili, Ramin Jaberi

Abstract:

In this project a new procedure has been introduced for utilizing digitally reconstructed radiograph from MRI images in Brachytherapy treatment planning. This procedure enables us to localize the tumor volume and delineate the extent of critical structures in vicinity of tumor volume. The aim of this project was to improve the accuracy of dose delivered to targets of interest in 2D treatment planning system.

Keywords: brachytherapy, cervix, digitally reconstructed radiographs, lymph node

Procedia PDF Downloads 501

Authors: Lubomir Vecera, Tomas Gabrhelik, Benjamin Tolmaci, Josef Srovnal, Emil Berta, Petr Prasil, Petr Stourac

Abstract:

Cancer is the second leading cause of death worldwide and colon cancer is the second most common type of cancer. Currently, there are only a few studies evaluating the effect of postoperative analgesia on the prognosis of patients undergoing radical colon cancer surgery. Postoperative analgesia in patients undergoing colon cancer surgery is usually managed in two ways, either with strong opioids (morphine, piritramide) or epidural analgesia. In our prospective study, we evaluated the effect of postoperative analgesia on the presence of circulating tumor cells or minimal residual disease after colon cancer surgery. A total of 60 patients who underwent radical colon cancer surgery were enrolled in this prospective, randomized, two-center study. Patients were randomized into three groups, namely piritramide, morphine and postoperative epidural analgesia. We evaluated the presence of carcinoembryonic antigen (CEA) and cytokeratin 20 (CK-20) mRNA positive circulating tumor cells in peripheral blood before surgery, immediately after surgery, on postoperative day two and one month after surgery. The presence of circulating tumor cells was assessed by quantitative real-time reverse transcriptase-polymerase chain reaction (qRT-PCR). In the priritramide postoperative analgesia group, the presence of CEA mRNA positive cells was significantly lower on a postoperative day two compared to the other groups (p=0.04). The value of CK-20 mRNA positive cells was the same in all groups on all days. In all groups, both types of circulating tumor cells returned to normal levels one month after surgery. Demographic and baseline clinical characteristics were similar in all groups. Compared with morphine and epidural analgesia, piritramide significantly reduces the amount of CEA mRNA positive circulating tumor cells after radical colon cancer surgery.

Keywords: cancer progression, colon cancer, minimal residual disease, perioperative analgesia.

Procedia PDF Downloads 156

Authors: Gabriele Ciasca, Tanya E. Sassun, Eleonora Minelli, Manila Antonelli, Massimiliano Papi, Antonio Santoro, Felice Giangaspero, Roberto Delfini, Marco De Spirito

Abstract:

Glioblastoma multiforme (GBM) is an extremely aggressive brain tumor, characterized by a diffuse infiltration of neoplastic cells into the brain parenchyma. Although rarely considered, mechanical cues play a key role in the infiltration process that is extensively mediated by the tumor microenvironment stiffness and, more in general, by the occurrence of aberrant interactions between neoplastic cells and the extracellular matrix (ECM). Here we provide a nano-mechanical characterization of the viscoelastic response of human GBM tissues by indentation-type atomic force microscopy. High-resolution elasticity maps show a large difference between the biomechanics of GBM tissues and the healthy peritumoral regions, opening possibilities to optimize the tumor resection area. Moreover, we unveil the nanomechanical signature of necrotic regions and anomalous vasculature, that are two major hallmarks useful for glioma staging. Actually, the morphological grading of GBM relies mainly on histopathological findings that make extensive use of qualitative parameters. Our findings have the potential to positively impact on the development of novel quantitative methods to assess the tumor grade, which can be used in combination with conventional histopathological examinations. In order to provide a more in-depth description of the role of mechanical cues in tumor progression, we compared the nano-mechanical fingerprint of GBM tissues with that of grade-I (WHO) meningioma, a benign lesion characterized by a completely different growth pathway with the respect to GBM, that, in turn hints at a completely different role of the biomechanical interactions.

Keywords: AFM, nano-mechanics, nanomedicine, brain tumors, glioblastoma

Procedia PDF Downloads 314

Authors: Regina M. Chiechio, Rémi Leguevél, Helene Solhi, Marie Madeleine Gueguen, Stephanie Dutertre, Xavier, Jean-Pierre Bazureau, Olivier Mignen, Pascale Even-Hernandez, Paolo Musumeci, Maria Jose Lo Faro, Valerie Marchi

Abstract:

Thanks to their ultra-small size, high electron density, and low toxicity, gold nanoclusters (Au NCs) have unique photoelectrochemical and luminescence properties that make them very interesting for diagnosis bio-imaging and theranostics. These applications require control of their delivery and interaction with cells; for this reason, the surface chemistry of Au NCs is essential to determine their interaction with the targeted biological objects. Here we demonstrate their ability as markers of pancreatic tumor cells. By functionalizing the surface of the NCs with a recognition peptite (U11), the nanostructures are able to preferentially bind to pancreatic cancer cells via a receptor (uPAR) overexpressed by these cells. Furthermore, the NCs can mark even the nucleus without the need of fixing the cells. These nanostructures can therefore be used as a non-toxic, multivalent luminescent platform, capable of selectively recognizing tumor cells for bioimaging, drug delivery, and radiosensitization.

Keywords: gold nanoclusters, luminescence, biomarkers, pancreatic cancer, biomedical applications, bioimaging, fluorescent probes, drug delivery

Procedia PDF Downloads 116

Authors: Veronika Zivicova, Petr Broz, Zdenek Fik, Alzbeta Mifkova, Jan Plzak, Zdenek Cada, Herbert Kaltner, Jana Fialova Kucerova, Hans-Joachim Gabius, Karel Smetana Jr.

Abstract:

The possibility to determine genome-wide expression profiles of cells and tissues opens a new level of analysis in the quest to define dysregulation in malignancy and thus identify new tumor markers. Toward this long-term aim, we here address two issues on this level for head and neck cancer specimen: i) defining profiles in different regions, i.e. the tumor, the transition zone and normal control and ii) comparing complete data sets for seven individual patients. Special focus in the flanking immunohistochemical part is given to adhesion/growth-regulatory galectins that upregulate chemo- and cytokine expression in an NF-κB-dependent manner, to these regulators and to markers of differentiation, i.e. keratins. The detailed listing of up- and down-regulations, also available in printed form (1), not only served to unveil new candidates for testing as marker but also let the impact of the tumor in the transition zone become apparent. The extent of interindividual variation raises a strong cautionary note on assuming uniformity of regulatory events, to be noted when considering therapeutic implications. Thus, a combination of test targets (and a network analysis for galectins and their downstream effectors) is (are) advised prior to reaching conclusions on further perspectives.

Keywords: galectins, genome scale sequencing, squamous cell carcinoma, transition zone

Procedia PDF Downloads 208

Authors: Mohammadreza Hedyehzadeh, Mahdi Yousefi

Abstract:

Colon cancer is one of the most common cancer, which predicted to increase its prevalence due to the bad eating habits of peoples. Nowadays, due to the busyness of people, the use of fast foods is increasing, and therefore, diagnosis of this disease and its treatment are of particular importance. To determine the best treatment approach for each specific colon cancer patients, the oncologist should be known the stage of the tumor. The most common method to determine the tumor stage is TNM staging system. In this system, M indicates the presence of metastasis, N indicates the extent of spread to the lymph nodes, and T indicates the size of the tumor. It is clear that in order to determine all three of these parameters, an imaging method must be used, and the gold standard imaging protocols for this purpose are CT and PET/CT. In CT imaging, due to the use of X-rays, the risk of cancer and the absorbed dose of the patient is high, while in the PET/CT method, there is a lack of access to the device due to its high cost. Therefore, in this study, we aimed to estimate the tumor size and the extent of its spread to the lymph nodes using MR images. More than 1300 MR images collected from the TCIA portal, and in the first step (pre-processing), histogram equalization to improve image qualities and resizing to get the same image size was done. Two expert radiologists, which work more than 21 years on colon cancer cases, segmented the images and extracted the tumor region from the images. The next step is feature extraction from segmented images and then classify the data into three classes: T0N0، T3N1 و T3N2. In this article, the VGG-16 convolutional neural network has been used to perform both of the above-mentioned tasks, i.e., feature extraction and classification. This network has 13 convolution layers for feature extraction and three fully connected layers with the softmax activation function for classification. In order to validate the proposed method, the 10-fold cross validation method used in such a way that the data was randomly divided into three parts: training (70% of data), validation (10% of data) and the rest for testing. It is repeated 10 times, each time, the accuracy, sensitivity and specificity of the model are calculated and the average of ten repetitions is reported as the result. The accuracy, specificity and sensitivity of the proposed method for testing dataset was 89/09%, 95/8% and 96/4%. Compared to previous studies, using a safe imaging technique (MRI) and non-use of predefined hand-crafted imaging features to determine the stage of colon cancer patients are some of the study advantages.

Keywords: colon cancer, VGG-16, magnetic resonance imaging, tumor size, lymph node metastasis

Procedia PDF Downloads 35

Authors: L. M. Al-Harbi, A. M. Shokry, J. S. M. Sabir, A. Chaudhary, J. Manikandan, K. S. Saini

Abstract:

Breast cancer is the second most common cause of cancer death worldwide and is the most common malignancy among Saudi females. During breast carcinogenesis, a wide-array of cytogenetic changes involving deletions, or amplification, or translocations, of part or whole of chromosome regions have been observed. Because of the limitations of various earlier technologies, newer tools are developed to scan for changes at the genomic level. Recently, Array Comparative Genomic Hybridization (aCGH) technique has been applied for detecting segmental genomic alterations at molecular level. In this study, aCGH was performed on twenty breast cancer tumors and their matching non-tumor (normal) counterparts using the Agilent 2x400K. Several regions were identified to be either amplified or deleted in a tumor-specific manner. Most frequent alterations were amplification of chromosome 1q, chromosome 8q, 20q, and deletions at 16q were also detected. The amplification of genetic events at 1q and 8q were further validated using FISH analysis using probes targeting 1q25 and 8q (MYC gene). The copy number changes at these loci can potentially cause a significant change in the tumor behavior, as deletions in the E-Cadherin (CDH1)-tumor suppressor gene as well as amplification of the oncogenes-Aurora Kinase A. (AURKA) and MYC could make these tumors highly metastatic. This study validates the use of aCGH in Saudi breast cancer patients and sets the foundations necessary for performing larger cohort studies searching for ethnicity-specific biomarkers and gene copy number variations.

Keywords: breast cancer, molecular biology, ecology, environment

Procedia PDF Downloads 349

Authors: Luiz Carlos Wrobel, Matjaz Hribersek, Jure Marn, Jurij Iljaz

Abstract:

Dynamic thermography has been clinically proven to be a valuable diagnostic technique for skin tumor detection as well as for other medical applications such as breast cancer diagnostics, diagnostics of vascular diseases, fever screening, dermatological and other applications. Thermography for medical screening can be done in two different ways, observing the temperature response under steady-state conditions (passive or static thermography), and by inducing thermal stresses by cooling or heating the observed tissue and measuring the thermal response during the recovery phase (active or dynamic thermography). The numerical modelling of heat transfer phenomena in biological tissue during dynamic thermography can aid the technique by improving process parameters or by estimating unknown tissue parameters based on measured data. This paper presents a nonlinear numerical model of multilayer skin tissue containing a skin tumor, together with the thermoregulation response of the tissue during the cooling-rewarming processes of dynamic thermography. The model is based on the Pennes bioheat equation and solved numerically by using a subdomain boundary element method which treats the problem as axisymmetric. The paper includes computational tests and numerical results for Clark II and Clark IV tumors, comparing the models using constant and temperature-dependent thermophysical properties, which showed noticeable differences and highlighted the importance of using a local thermoregulation model.

Keywords: boundary element method, dynamic thermography, static thermography, skin tumor diagnostic

Procedia PDF Downloads 75

Authors: Anna Cameron, Chunxia Zhao, Haofei Wang, Yun Liu, Guang Ze Yang

Abstract:

Since the first publication in 1775, cancer research has built a comprehensive understanding of how cellular components of the tumor niche promote disease development. However, only within the last decade has research begun to establish the impact of non-cellular components of the niche, particularly the extracellular matrix (ECM). The ECM, a three-dimensional scaffold that sustains the tumor microenvironment, plays a crucial role in disease progression. Cancer cells actively deregulate and remodel the ECM to establish a tumor-promoting environment. Recent work has highlighted the need to further our understanding of the complexity of this cancer-ECM relationship. In vitro models use hydrogels to mimic the ECM, as hydrogel matrices offer biological compatibility and stability needed for long term cell culture. However, natural hydrogels are being used in these models verbatim, without tuning their biophysical characteristics to achieve pathophysiological relevance, thus limiting their broad use within cancer research. The biophysical attributes of these gels dictate cancer cell proliferation, invasion, metastasis, and therapeutic response. Evaluating the three most widely used natural hydrogels, Matrigel, collagen, and agarose gel, the permeability, stiffness, and pore-size of each gel were measured and compared to the in vivo environment. The pore size of all three gels fell between 0.5-6 µm, which coincides with the 0.1-5 µm in vivo pore size found in the literature. However, the stiffness for hydrogels able to support cell culture ranged between 0.05 and 0.3 kPa, which falls outside the range of 0.3-20,000 kPa reported in the literature for an in vivo ECM. Permeability was ~100x greater than in vivo measurements, due in large part to the lack of cellular components which impede permeation. Though, these measurements prove important when assessing therapeutic particle delivery, as the ECM permeability decreased with increasing particle size, with 100 nm particles exhibiting a fifth of the permeability of 10 nm particles. This work explores ways of adjusting the biophysical characteristics of hydrogels by changing protein concentration and the trade-off, which occurs due to the interdependence of these factors. The global aim of this work is to produce a more pathophysiologically relevant model for each tumor type.

Keywords: cancer, extracellular matrix, hydrogel, microfluidic

Procedia PDF Downloads 65

Authors: Behrooz Nikahval, Mohammad Saeed Ahrari-Khafi, Sakineh Behroozpoor, Saeed Nazifi

Abstract:

Osteoarthritis (OA) is a progressive and degenerative condition of the articular cartilage and other joints’ structures. It is essential to diagnose this condition as early as possible. The present research was performed to measure the Osteoprotegrin (OPG) and Tumor Necrosis Factor α (TNF-α) in synovial fluid and blood serum of dogs with surgically transected cruciate ligament as a model of OA, to evaluate if measuring of these parameters can be used as a way of early diagnosis of OA. In the present study, four mature, clinically healthy dogs were selected to investigate the effect of experimental OA, on OPG and TNF-α as a way of early detection of OA. OPG and TNF-α were measured in synovial fluid and blood serum on days 0, 14, 28, 90 and 180 after surgical transaction of cranial cruciate ligament in one stifle joint. Statistical analysis of the results showed that there was a significant increase in TNF-α in both synovial fluid and blood serum. OPG showed a decrease two weeks after OA induction. However, it fluctuated afterward. In conclusion, TNF-α could be used in both synovial fluid and blood serum as a way of early detection of OA; however, further research still needs to be conducted on OPG values in OA detection.

Keywords: osteoarthritis, osteoprotegrin, tumor necrosis factor α, synovial fluid, serum, dog

Procedia PDF Downloads 292

Authors: Mayssa Bensalah, Atef Boujelben, Mouna Baklouti, Mohamed Abid

Abstract:

Image segmentation has a fundamental role in analysis and interpretation for many applications. The automated segmentation of organs and tissues throughout the body using computed imaging has been rapidly increasing. Indeed, it represents one of the most important parts of clinical diagnostic tools. In this paper, we discuss a thorough literature review of recent methods of tumour segmentation from medical images which are briefly explained with the recent contribution of various researchers. This study was followed by comparing these methods in order to define new directions to develop and improve the performance of the segmentation of the tumour area from medical images.

Keywords: features extraction, image segmentation, medical images, tumor detection

Procedia PDF Downloads 134