Search results for: metastatic ovarian tumor

Authors: Mrinal Kanti Bhowmik, Kakali Das Jr., Barin Kumar De, Debotosh Bhattacharjee

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Breast cancer is the most common cancer and a leading cause of death for women in the 35 to 55 age group. Early detection of breast cancer can decrease the mortality rate of breast cancer. Mammography is considered as a ‘Gold Standard’ for breast cancer detection and a very popular modality, presently used for breast cancer screening and detection. The screening of digital mammograms often leads to over diagnosis and a consequence to unnecessary traumatic & painful biopsies. For that reason recent studies involving the use of thermal imaging as a screening technique have generated a growing interest especially in cases where the mammography is limited, as in young patients who have dense breast tissue. Tumor is a significant sign of breast cancer in both mammography and thermography. The tumors are complex in structure and they also exhibit a different statistical and textural features compared to the breast background tissue. Fractal geometry is a geometry which is used to describe this type of complex structure as per their main characteristic, where traditional Euclidean geometry fails. Over the last few years, fractal geometrics have been applied mostly in many medical image (1D, 2D, or 3D) analysis applications. In breast cancer detection using digital mammogram images, also it plays a significant role. Fractal is also used in thermography for early detection of the masses using the thermal texture. This paper presents an overview of the recent aspects and initiatives of fractals in breast cancer detection in both mammography and thermography. The scope of fractal geometry in automatic breast cancer detection using digital mammogram and thermogram images are analysed, which forms a foundation for further study on application of fractal geometry in medical imaging for improving the efficiency of automatic detection.

Keywords: fractal, tumor, thermography, mammography

Procedia PDF Downloads 379

Authors: Javier Enciso-Benavides, Fredy Fabian, Carlos Castaneda, Luis Alfaro, Alex Choque, Aparicio Aguilar, Javier Enciso

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Background: The use of biomarkers in breast cancer diagnosis, therapy, and prognosis has gained increasing interest. Cancer stem cells (CSCs) are a subpopulation of tumor cells that can drive tumor initiation and may cause relapse. Therefore, due to the importance of diagnosis, therapy, and prognosis, several biomarkers that characterize CSCs have been identified; however, in treatment-naïve triple-negative breast tumors, there is an urgent need to identify new biomarkers and therapeutic targets. According to this, the aim of this study was to identify serum proteins associated with cancer stem cells and pluripotency in women with triple-negative breast tumors in order to subsequently identify a biomarker for this type of breast tumor. Material and Methods: Whole blood samples from 12 women with histopathologically diagnosed triple-negative breast tumors were used after obtaining informed consent from the patient. Blood serum was obtained by conventional procedure and frozen at -80ºC. Identification of cancer stem cell-associated proteins was performed by matrix-assisted laser desorption/ionisation-assisted laser desorption/ionisation mass spectrometry (MALDI-TOF MS), protein analysis was obtained using the AB Sciex TOF/TOF™ 5800 system (AB Sciex, USA). Sequences not aligned by ProteinPilot™ software were analyzed by Protein BLAST. Results: The following proteins related to pluripotency and cancer stem cells were identified by MALDI TOF/TOF mass spectrometry: A-chain, Serpin A12 [Homo sapiens], AIEBP [Homo sapiens], Alpha-one antitrypsin, AT {internal fragment} [human, partial peptide, 20 aa] [Homo sapiens], collagen alpha 1 chain precursor variant [Homo sapiens], retinoblastoma-associated protein variant [Homo sapiens], insulin receptor, CRA_c isoform [Homo sapiens], Hydroxyisourate hydrolase [Streptomyces scopuliridis], MUCIN-6 [Macaca mulatta], Alpha-actinin-3 [Chrysochloris asiatica], Polyprotein M, CRA_d isoform, partial [Homo sapiens], Transcription factor SOX-12 [Homo sapiens]. Recommendations: The serum proteins identified in this study should be investigated in the exosome of triple-negative breast cancer stem cells and in the blood serum of women without breast cancer. Subsequently, proteins found only in the blood serum of women with triple-negative breast cancer should be identified in situ in triple-negative breast cancer tissue in order to identify a biomarker to study the evolution of this type of cancer, or that could be a therapeutic target. Conclusions: Eleven cancer stem cell-related serum proteins were identified in 12 women with triple-negative breast cancer, of which MUCIN-6, retinoblastoma-associated protein variant, transcription factor SOX-12, and collagen alpha 1 chain are the most representative and have not been studied so far in this type of breast tumor. Acknowledgement: This work was supported by Proyecto CONCYTEC–Banco Mundial “Mejoramiento y Ampliacion de los Servicios del Sistema Nacional de Ciencia Tecnología e Innovacion Tecnologica” 8682-PE (104-2018-FONDECYT-BM-IADT-AV).

Keywords: triple-negative breast cancer, MALDI TOF/TOF MS, serum proteins, cancer stem cells

Procedia PDF Downloads 203

Authors: Rupali Bhatia, Deepthi Nair, Geetika Khanna, Seema Singhal

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Introduction: Genital tract tuberculosis is a chronic disease (caused by reactivation of organisms from systemic distribution of Mycobacterium tuberculosis) that often presents with low grade symptoms and non-specific complaints. Patients with genital tuberculosis are usually young women seeking workup and treatment for infertility. Infertility is the commonest presentation due to involvement of the fallopian tubes, endometrium and ovarian damage with poor ovarian volume and reserve. The diagnosis of genital tuberculosis is difficult because of the fact that it is a silent invader of genital tract. Since tissue cannot be obtained from fallopian tubes, the diagnosis is made by isolation of bacilli from endometrial tissue obtained by endometrial biopsy curettage and/or aspiration. Problems are associated with sampling technique as well as diagnostic modality due to lack of adequate sample volumes and the segregation of the sample for various diagnostic tests resulting in non-uniform distribution of microorganisms. Moreover, lack of an efficient sampling technique universally applicable for all specific diagnostic tests contributes to the diagnostic challenges. Endometrial sampling plays a key role in accurate diagnosis of female genital tuberculosis. It may be done by 2 methods viz. endometrial curettage and endometrial aspiration. Both endometrial curettage and aspirate have their own limitations as curettage picks up strip of the endometrium from one of the walls of the uterine cavity including tubal osteal areas whereas aspirate obtains total tissue with exfoliated cells present in the secretory fluid of the endometrial cavity. Further, sparse and uneven distribution of the bacilli remains a major factor contributing to the limitations of the techniques. The sample that is obtained by either technique is subjected to histopathological examination, AFB staining, culture and PCR. Aim: Comparison of the sampling techniques viz. endometrial biopsy curettage and endometrial aspiration using different laboratory methods of histopathology, cytology, microbiology and molecular biology. Method: In a hospital based observational study, 75 Indian females suspected of genital tuberculosis were selected on the basis of inclusion criteria. The women underwent endometrial tissue sampling using Novaks biopsy curette and Karmans cannula. One part of the specimen obtained was sent in formalin solution for histopathological testing and another part was sent in normal saline for acid fast bacilli smear, culture and polymerase chain reaction. The results so obtained were correlated using coefficient of correlation and chi square test. Result: Concordance of results showed moderate agreement between both the sampling techniques. Among HPE, AFB and PCR, maximum sensitivity was observed for PCR, though the specificity was not as high as other techniques. Conclusion: Statistically no significant difference was observed between the results obtained by the two sampling techniques. Therefore, one may use either EA or EB to obtain endometrial samples and avoid multiple sampling as both the techniques are equally efficient in diagnosing genital tuberculosis by HPE, AFB, culture or PCR.

Keywords: acid fast bacilli (AFB), histopatholgy examination (HPE), polymerase chain reaction (PCR), endometrial biopsy curettage

Procedia PDF Downloads 322

Authors: D. O. Miranda, L. R. Azevedo, J. F. C. Cordeiro, A. H. Dos Santos, S. F. Lisboa, F. S. Guimarães, G. S. Bisson

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Background: The Colorectal cancer (CRC) is one of the most common cancers and the fourth leading cause of cancer death in the world. The prevalence of psychiatric-disorders among CRC patients, mainly depression, is high, resulting in impaired quality of life and side effects of primary treatment. High levels of proinflammatory cytokines at tumor microenvironment is a feature of CRC and the literature suggests that those mediators could contribute to the development of psychiatric disorders. Nevertheless, the ability of tumor-associated biological processes to affect the central nervous system (CNS) has only recently been explored in the context of symptoms of depression and is still not well understood. Therefore, the aim of the present study was to test the hypothesis that depressive-like behavior in an experimental model of CCR induced by N-methyl-N-nitro-N-nitrosoguanidine (MNNG) was correlated to proinflammatory profile in the periphery and in the brain. Methods: Colorectal carcinogenesis was induced in adult C57BL/6 mice (n=12) by administration of MNNG (5mg/kg, 0.1ml/intrarectal instillation) 2 times a week, for 2 week. Control group (n=12) received saline (0.1ml/intrarectal instillation). Eight weeks after beginning of MNNG administration animals were submitted to the forced swim test (FST) and the sucrose preference test for evaluation, respectively, of depressive- and anhedonia-like behaviors. After behavioral evaluation, the colon was collected and brain regions dissected (cortex-C, striatum-ST and hippocampus-HIP) for posterior evaluation of cytokine levels (IL-1β, IL-10, IL-17, and CX3CL1) by ELISA. Results: MNNG induced depressive-like behavior, represented by increased immobility time in the FST (Student t test, p < 0.05) and lower sucrose preference (Student t test, p < 0.05). Moreover, there were increased levels of IL-1β, IL-17 and CX3CL1 in the colonic tissue (Student t test, p < 0.05) and in the brain (IL-1 β in the ST and HIP, Student t test, p < 0.05; IL-17 and CX3CL1 in the C and HIP, p < 0.05). IL-10 levels, in contrast, were decreased in both the colon (p < 0.05) and the brain (C and HIP, p < 0.05). Conclusions: The results obtained in the present work support the notion that tumor growth induces neuroinflammation in stress-related brain regions and depressive-like behavior, which could be related to the high incidence of depression in colorectal carcinogenesis. This work have important clinical and research implications, taken into account that cytokine levels may be a marker promissory for the developing depression in CRC patients. New therapeutic strategies to assist in alleviating mental suffering in cancer patients might result from a better understanding of the role of cytokines in the pathophysiology of depression in these subjects.

Keywords: cytokines, brain, depression, colorectal cancer

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Authors: Sayed Ali Garossi, Azar Heidarizadi, Shahla Mohammad Ganji

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Context: Colorectal cancer is the second type of cancer-related mortality globally. Expression of cas8 (caspase 8) is closely connected to growth and metastasis of colorectal cancer.Cas8/Rip1 plays a vital role in the apoptosis pathway and resistance to chemotherapy. The aim of the present study is to investigate the pattern of gene expression in colorectal cancer and compare the differences using Real-Time PCR to find a potential biomarker candidate for colorectal cancer. Methodology: This study conducted real-time PCR to evaluate gene expression of Cas8 in colorectal cancer patients. The gene-specific primer sequences exon–exon junction was designed by OLIGO7 software for the expression of the gene under investigation. Forty-six patient samples without any chemotherapy were selected, including tumoral tissue and adjacent normal tissue samples. The age of the patients was 50 and the size of the tumors was 5.5 cm. The categories were before and after age 50. Findings: Here, we found that Caspase 8 was overexpressed in CRC tissues compared to corresponding adjacent colon tissues (Cas8: 5.2 vs. 1 ratio); high expression of Cas8 was associated with poor overall survival and independent risk factors for the prognosis of CRC patients. Conclusion: In conclusion, our study pioneered the reporting of high Casp8 expression as a predictor of poor prognosis and chemical resistance in CRC patients.Cas8 overexpression suppressed Cas 8 / Rip1-dependent apoptosis and activated the proliferation of tumor cells by activating necroptosis. The necroptosis pathway has also emerged as a new approach to anti-tumor in cancer treatment.

Keywords: Cas8, necroptosis, apoptosis, Real-Time PCR

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Authors: Maymona Al-Husari, Craig Murdoch, Steven Webb

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Some tumors are known to exhibit an extracellular pH that is more acidic than the intracellular, creating a 'reversed pH gradient' across the cell membrane and this has been shown to affect their invasive and metastatic potential. Tumour hypoxia also plays an important role in tumour development and has been directly linked to both tumour morphology and aggressiveness. In this paper, we present a hybrid mathematical model of intracellular pH regulation that examines the effect of oxygen and pH on tumour growth and morphology. In particular, we investigate the impact of pH regulatory mechanisms on the cellular pH gradient and tumour morphology. Analysis of the model shows that: low activity of the Na+/H+ exchanger or a high rate of anaerobic glycolysis can give rise to a 'fingering' tumour morphology; and a high activity of the lactate/H+ symporter can result in a reversed transmembrane pH gradient across a large portion of the tumour mass. Also, the reversed pH gradient is spatially heterogenous within the tumour, with a normal pH gradient observed within an intermediate growth layer, that is the layer between the proliferative inner and outermost layer of the tumour.

Keywords: acidic pH, cellular automaton, ebola, tumour growth

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Authors: Sreeparna Majee, G. C. Shit

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A study on targeted drug delivery is carried out in an unsteady flow of blood infused with magnetic NPs (nanoparticles) with an aim to understand the flow pattern and nanoparticle aggregation in a diseased arterial segment having stenosis. The magnetic NPs are supervised by the magnetic field which is significant for therapeutic treatment of arterial diseases, tumor and cancer cells and removing blood clots. Coupled thermal energy have also been analyzed by considering dissipation of energy because of the application of the magnetic field and the viscosity of blood. Simulation technique used to solve the mathematical model is vorticity-stream function formulations in the diseased artery. An elevation in SLP (Specific loss power) is noted in the aortic bloodstream when the agglomeration of nanoparticles is higher. This phenomenon has potential application in the treatment of hyperthermia. The study focuses on the lowering of WSS (Wall Shear Stress) with increasing particle concentration at the downstream of the stenosis which depicts the vigorous flow circulation zone. These low shear stress regions prolong the residing time of the nanoparticles carrying drugs which soaks up the LDL (Low Density Lipoprotein) deposition. Moreover, an increase in NP concentration enhances the Nusselt number which marks the increase of heat transfer from the arterial wall to the surrounding tissues to destroy tumor and cancer cells without affecting the healthy cells. The results have a significant influence in the study of medicine, to treat arterial diseases such as atherosclerosis without the need for surgery which can minimize the expenditures on cardiovascular treatments.

Keywords: magnetic nanoparticles, blood flow, atherosclerosis, hyperthermia

Procedia PDF Downloads 132

Authors: Jae Won Lee, Kyung Hyun Min, Hong Jae Lee, Sang Cheon Lee

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To date, imaging techniques have attracted much attention in medicine because the detection of diseases at an early stage provides greater opportunities for successful treatment. Consequently, over the past few decades, diverse imaging modalities including magnetic resonance (MR), positron emission tomography, computed tomography, and ultrasound (US) have been developed and applied widely in the field of clinical diagnosis. However, each of the above-mentioned imaging modalities possesses unique strengths and intrinsic weaknesses, which limit their abilities to provide accurate information. Therefore, multimodal imaging systems may be a solution that can provide improved diagnostic performance. Among the current medical imaging modalities, US is a widely available real-time imaging modality. It has many advantages including safety, low cost and easy access for patients. However, its low spatial resolution precludes accurate discrimination of diseased region such as cancer sites. In contrast, MR has no tissue-penetrating limit and can provide images possessing exquisite soft tissue contrast and high spatial resolution. However, it cannot offer real-time images and needs a comparatively long imaging time. The characteristics of these imaging modalities may be considered complementary, and the modalities have been frequently combined for the clinical diagnostic process. Biominerals such as calcium carbonate (CaCO3) and calcium phosphate (CaP) exhibit pH-dependent dissolution behavior. They demonstrate pH-controlled drug release due to the dissolution of minerals in acidic pH conditions. In particular, the application of this mineralization technique to a US contrast agent has been reported recently. The CaCO3 mineral reacts with acids and decomposes to generate calcium dioxide (CO2) gas in an acidic environment. These gas-generating mineralized nanoparticles generated CO2 bubbles in the acidic environment of the tumor, thereby allowing for strong echogenic US imaging of tumor tissues. On the basis of this previous work, it was hypothesized that the loading of MR contrast agents into the CaCO3 mineralized nanoparticles may be a novel strategy in designing a contrast agent for dual imaging. Herein, CaCO3 mineralized nanoparticles that were capable of generating CO2 bubbles to trigger the release of entrapped MR contrast agents in response to tumoral acidic pH were developed for the purposes of US and MR dual-modality imaging of tumors. Gd2O3 nanoparticles were selected as an MR contrast agent. A key strategy employed in this study was to prepare Gd2O3 nanoparticle-loaded mineralized nanoparticles (Gd2O3-MNPs) using block copolymer-templated CaCO3 mineralization in the presence of calcium cations (Ca2+), carbonate anions (CO32-) and positively charged Gd2O3 nanoparticles. The CaCO3 core was considered suitable because it may effectively shield Gd2O3 nanoparticles from water molecules in the blood (pH 7.4) before decomposing to generate CO2 gas, triggering the release of Gd2O3 nanoparticles in tumor tissues (pH 6.4~7.4). The kinetics of CaCO3 dissolution and CO2 generation from the Gd2O3-MNPs were examined as a function of pH and pH-dependent in vitro magnetic relaxation; additionally, the echogenic properties were estimated to demonstrate the potential of the particles for the tumor-specific US and MR imaging.

Keywords: calcium carbonate, mineralization, ultrasound imaging, magnetic resonance imaging

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Authors: H. F. Hozyen, A. M. Abo-El Maaty

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Heat stress is a recognized problem causing huge economic losses to the buffalo breeders as well as dairy industry. The aim of the present work was to study the pattern of vitamin C and nitric oxide in follicular fluid of buffalo during different seasons of the year considering phase of estrous cycle. This study was conducted on 208 cyclic buffaloes slaughtered at Al-Qaliobia governorate, Egypt, over one year. The obtained results revealed that vitamin C in follicular fluid was significantly lower in summer than winter and spring. On the other hand, nitric oxide (NO) was significantly higher in summer and autumn than winter and spring. Both vitamin C and NO did not differ significantly between follicular and luteal phases. In conclusion, the present study revealed that alterations in concentrations of follicular fluid vitamin C and NO that occur in summer could be related to low summer fertility in buffalo.

Keywords: Buffalo, follicular fluid, vitamin C, nitric oxide, heat stress

Procedia PDF Downloads 325

Authors: Sadaf Salek

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Introduction: Cats are susceptible to various health conditions, and one such ailment that can affect their oral health is epulis in their lips. Epulis refers to a benign tumor or growth that can develop in different areas of a cat's mouth, including the lips. While epulis is not life-threatening, it can still cause discomfort and affect a cat's overall quality of life. This essay aims to delve into the causes, symptoms, and treatment options for epulis in cat's lips, shedding light on this lesser-known oral condition. Causes: Epulis in a cat's lips can have several causes. Firstly, genetic predisposition plays a significant role, with certain breeds being more prone to developing these growths. Secondly, chronic irritation to the mouth, such as from dental diseases or foreign objects, can also contribute to the development of epulis. Lastly, hormonal imbalances, specifically an excess of estrogen, have been associated with the occurrence of these tumors in cats. Understanding these causes can help cat owners take preventive measures to reduce the risk of epulis in their feline companions. Symptoms: Identifying the symptoms of epulis in a cat's lips is vital for early intervention and effective treatment. The most common symptoms include swelling, redness, and the presence of a visible growth or lump on the lip. Cats with epulis may also exhibit drooling, difficulty eating, and a reluctance to groom themselves. Any change in eating habits or oral behavior should not be overlooked and prompt a visit to the veterinarian for a thorough examination. Treatment ptions: When it comes to treating epulis in a cat's lips, various options are available, depending on the size, location, and characteristics of the growth. The primary treatment involves surgical removal of the tumor. This procedure should be performed by a qualified veterinarian, ensuring complete excision of the mass while preserving as much healthy tissue as possible. In some cases, radiation therapy may be necessary, especially if the tumor is large or aggressive. Additionally, a veterinarian may recommend oral hygiene care and regular dental cleaning to prevent further growths and maintain the cat's oral health. Prevention and Care: Preventing epulis in a cat's lips is not always possible, especially if genetic factors are involved. However, certain preventive measures can minimize the risk of these growths. Maintaining good oral hygiene through regular brushing and the use of appropriate dental products can help prevent chronic irritation and dental diseases. Routine veterinary check-ups should also include thorough oral examinations to detect any abnormal growths or changes in the mouth at an early stage. Pet owners should be observant and seek veterinary care promptly for any signs of discomfort or changes in eating habits. Conclusion: Epulis in a cat's lips is a condition that requires attention and proper treatment. Understanding the causes, identifying symptoms, and exploring treatment options are of utmost importance to help improve a cat's oral health and overall well-being.

Keywords: fibroma, cat, lip, epulis

Procedia PDF Downloads 41

Authors: H. Hadjeris, R. B. Ghoul, Lekhlaf, M. Nebbal

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Introduction: Adenoid cystic carcinomas of the lacrimal gland or orbital cylindroma constitute the second cause of epithelial tumors of this gland. It is a malignant tumor usually developed at the expense of the salivary glands; its orbital location is exceptional. It is a rare clinical entity, formidable by its malignancy and local aggressiveness; the recurrence rate is high. Materials and methods: Clinical case: 63 years old woman who presents with irreducible no pulsatile painful left exophthalmos with inflammatory chemosis and a decrease in visual acuity with a moderate intracranial hypertension syndrome that has been evolving for 03 months. Antecedent; a biopsy of the tumor was made; the histological examination was in favor of an adenoid cystic carcinoma of the lacrimal gland. Lesion assessment: computed tomography and brain MRI: show an intra and extra-conical mass; with sinus (ethmoido-frontal) and cerebral (left frontal) extension strongly enhanced after injection of contrast product surrounded by edema around the lesion, associated with left frontal bone lysis extension assessment: unremarkable treatment: Patient operated by left frontotemporal approach, a total exenteration was performed with macroscopically complete excision of the frontal lesion and wide frontal craniectomy with craniofacial reconstruction, followed by complementary radiotherapy. Results: The patient was seen again after 3 months in consultation; she does not present any signs in favor of a recurrence. Conclusion: Adenoid cystic carcinomas of the lacrimal gland are rare malignant tumors; they are very infiltrating and invasive. The prognosis is strongly linked to the treatment time.

Keywords: adenoid cystic, lacrimal gland, orbital location, fronto-temporal approac

Procedia PDF Downloads 67

Authors: Shuo Li, Yannick Coffinier, Chann Lagadec, Fabrizio Cleri, Katsuhiko Nishiguchi, Akira Fujiwara, Soo Hyeon Kim, Nicolas Clément

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The need for single cell detection and analysis techniques has increased in the past decades because of the heterogeneity of individual living cells, which increases the complexity of the pathogenesis of malignant tumors. In the search for early cancer detection, high-precision medicine and therapy, the technologies most used today for sensitive detection of target analytes and monitoring the variation of these species are mainly including two types. One is based on the identification of molecular differences at the single-cell level, such as flow cytometry, fluorescence-activated cell sorting, next generation proteomics, lipidomic studies, another is based on capturing or detecting single tumor cells from fresh or fixed primary tumors and metastatic tissues, and rare circulating tumors cells (CTCs) from blood or bone marrow, for example, dielectrophoresis technique, microfluidic based microposts chip, electrochemical (EC) approach. Compared to other methods, EC sensors have the merits of easy operation, high sensitivity, and portability. However, despite various demonstrations of low limits of detection (LOD), including aptamer sensors, arrayed EC sensors for detecting single-cell have not been demonstrated. In this work, a new technique based on 20-nm-thick nanopillars array to support cells and keep them at ideal recognition distance for redox-labeled aptamers grafted on the surface. The key advantages of this technology are not only to suppress the false positive signal arising from the pressure exerted by all (including non-target) cells pushing on the aptamers by downward force but also to stabilize the aptamer at the ideal hairpin configuration thanks to a confinement effect. With the first implementation of this technique, a LOD of 13 cells (with5.4 μL of cell suspension) was estimated. In further, the nanosupported cell technology using redox-labeled aptasensors has been pushed forward and fully integrated into a single-cell electrochemical aptasensor array. To reach this goal, the LOD has been reduced by more than one order of magnitude by suppressing parasitic capacitive electrochemical signals by minimizing the sensor area and localizing the cells. Statistical analysis at the single-cell level is demonstrated for the recognition of cancer cells. The future of this technology is discussed, and the potential for scaling over millions of electrodes, thus pushing further integration at sub-cellular level, is highlighted. Despite several demonstrations of electrochemical devices with LOD of 1 cell/mL, the implementation of single-cell bioelectrochemical sensor arrays has remained elusive due to their challenging implementation at a large scale. Here, the introduced nanopillar array technology combined with redox-labeled aptamers targeting epithelial cell adhesion molecule (EpCAM) is perfectly suited for such implementation. Combining nanopillar arrays with microwells determined for single cell trapping directly on the sensor surface, single target cells are successfully detected and analyzed. This first implementation of a single-cell electrochemical aptasensor array based on Brownian-fluctuating redox species opens new opportunities for large-scale implementation and statistical analysis of early cancer diagnosis and cancer therapy in clinical settings.

Keywords: bioelectrochemistry, aptasensors, single-cell, nanopillars

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Authors: Wendu Pang, Yaxin Luo, Junhong Li, Yu Zhao, Danni Cheng, Yufang Rao, Minzi Mao, Ke Qiu, Yijun Dong, Fei Chen, Jun Liu, Jian Zou, Haiyang Wang, Wei Xu, Jianjun Ren

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We aimed to compare the prognostic prediction value of positive lymph node number (PLNN) to the American Joint Committee on Cancer (AJCC) tumor, lymph node, and metastasis (TNM) staging system for patients with hypopharyngeal squamous cell carcinoma (HPSCC). A total of 826 patients with HPSCC from the Surveillance, Epidemiology, and End Results database (2004–2015) were identified and split into two independent cohorts: training (n=461) and validation (n=365). Univariate and multivariate Cox regression analyses were used to evaluate the prognostic effects of PLNN in patients with HPSCC. We further applied six Cox regression models to compare the survival predictive values of the PLNN and AJCC TNM staging system. PLNN showed a significant association with overall survival (OS) and cancer-specific survival (CSS) (P < 0.001) in both univariate and multivariable analyses, and was divided into three groups (PLNN 0, PLNN 1-5, and PLNN>5). In the training cohort, multivariate analysis revealed that the increased PLNN of HPSCC gave rise to significantly poor OS and CSS after adjusting for age, sex, tumor size, and cancer stage; this trend was also verified by the validation cohort. Additionally, the survival model incorporating a composite of PLNN and TNM classification (C-index, 0.705, 0.734) performed better than the PLNN and AJCC TNM models. PLNN can serve as a powerful survival predictor for patients with HPSCC and is a surrogate supplement for cancer staging systems.

Keywords: hypopharyngeal squamous cell carcinoma, positive lymph nodes number, prognosis, prediction models, survival predictive values

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Authors: Lola T. Alimkhodjaeva, Lola T. Zakirova, Soniya S. Ziyavidenova

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Background: Breast cancer occupies the first place among the cancer in women in the world. It is urgent today to study the role of molecular markers which are capable of predicting the dynamics and outcome of the disease. The aim of this study is to define the prognostic value of the content of estrogen receptor (ER), progesterone receptor (PgR), and amplification of HER-2 / neu oncoprotein by studying 3 and 5-year overall and relapse-free survival in 470 patients with primary operable and 280 patients with locally–advanced breast cancer. Materials and methods: Study results of 3 and 5-year overall and relapse-free survival, depending on the content of RE, PgR in primary operable patients showed that ER positive (+) and PgR (+) survival was 100 (96.2%) and 97.3 (94.6%), for ER negative (-) and PgR (-) - 69.2 (60.3%) and 65.4 (57.7%), for ER positive (+) and negative PgR (-) 87.4 (80.1%) and 81.5 (79.3%), for ER negative (-) and positive PgR (+) - 97.4 (93.4%) and 90.4 (88.5%), respectively. Survival results depended also on the level of HER-2 / neu expression. In patients with HER-2 / neu negative the survival rates were as follows: 98.6 (94.7%) and 96.2 (92.3%). In group of patients with the level of HER-2 / neu (2+) expression these figures were: 45.3 (44.3%) and 45.1 (40.2%), and in group of patients with the level of HER-2 / neu (3+) expression - 41.2 (33.1%) and 34.3 (29.4%). The combination of ER negative (-), PgR (-), HER-2 / neu (-) they were 27.2 (25.4%) and 19.5 (15.3%), respectively. In patients with locally-advanced breast cancer the results of 3 and 5-year OS and RFS for ER (+) and PgR (+) were 76.3 (69.3%) and 62.2 (61.4%), for ER (-) and RP (-) 29.1 (23.7%) and 18.3 (12.6%), for ER (+) and PgR (-) 61.2 (47.2%) and 39.4 (25.6%), for ER (-) and PgR (+) 54.3 (43.1%) and 41.3 (18.3%), respectively. The level of HER-2 / neu expression also affected the survival results. Therefore, in HER-2/ neu negative patients the survival rate was 74.1 (67.6%) and 65.1 (57.3%), with the level of expression (2+) 20.4 (14.2%) and 8.6 (6.4%), with the level of expression (3+) 6.2 (3.1%) and 1.2 (1.5%), respectively. The combination for ER, PgR, HER-2 / neu negative was 22.1 (14.3%) and 8.4 (1.2%). Conclusion: Thus, the presence of steroid hormone receptors in breast tumor tissues at primary operable and locally- advanced process as the lack of HER-2/neu oncoprotein correlates with the highest rates of 3- and 5-year overall and relapse-free survival. The absence of steroid hormone receptors as well as of HER-2/neu overexpression in malignant breast tissues significantly degrades the 3- and 5-year overall and relapse-free survival. Tumors with ER, PgR and HER-2/neu negative have the most unfavorable prognostics.

Keywords: breast cancer, estrogen receptor, oncoprotein, progesterone receptor

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Authors: Esra Turker, Umit Hakan Yildiz, Ahu Arslan Yildiz

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The key of regenerative medicine is mimicking natural three dimensional (3D) microenvironment of tissues by utilizing appropriate biomaterials. In this study, a synthetic biodegradable polymer; poly (L-lactide-co-ε-caprolactone) (PLLCL) and a natural polymer; collagen was used to mimic the biochemical structure of the natural extracellular matrix (ECM), and by means of electrospinning technique the real physical structure of ECM has mimicked. PLLCL/Collagen biocomposite scaffolds enables cell attachment, proliferation and nutrient transport through fabrication of micro to nanometer scale nanofibers. Biocomposite materials are commonly preferred due to limitations of physical and biocompatible properties of natural and synthetic materials. Combination of both materials improves the strength, degradation and biocompatibility of scaffold. Literature studies have shown that collagen is mostly solved with heavy chemicals, which is not suitable for cell culturing. To overcome this problem, a new approach has been developed in this study where polyvinylpyrrolidone (PVP) is used as co-electrospinning agent. PVP is preferred due to its water solubility, so PLLCL/collagen biocomposite scaffold can be easily and rapidly produced. Hydrolytic and enzymatic biodegradation as well as mechanical strength of scaffolds were examined in vitro. Cell adhesion, proliferation and cell morphology characterization studies have been performed as well. Further, on-chip drug screening analysis has been performed over 3D tumor models. Overall, the developed biocomposite scaffold was used for 3D tumor model formation and obtained results confirmed that developed model could be used for drug screening studies to predict clinical efficacy of a drug.

Keywords: biomaterials, 3D cell culture, drug screening, electrospinning, lab-on-a-chip, tissue engineering

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Authors: Sara Assi, Berthe Hayar, Claudio Pisano, Nadine Darwiche, Walid Saad

Abstract:

Nanomedicine, the application of nanotechnology to medicine, is an emerging discipline that has gained significant attention in recent years. Current breakthroughs in nanomedicine have paved the way to develop effective drug delivery systems that can be used to target cancer. The use of nanotechnology provides effective drug delivery, enhanced stability, bioavailability, and permeability, thereby minimizing drug dosage and toxicity. As such, the use of nanoparticle (NP) formulations in drug delivery has been applied in various cancer models and have shown to improve the ability of drugs to reach specific targeted sites in a controlled manner. Cancer is one of the major causes of death worldwide; in particular, colorectal cancer (CRC) is the third most common type of cancer diagnosed amongst men and women and the second leading cause of cancer related deaths, highlighting the need for novel therapies. Retinoids, consisting of natural and synthetic derivatives, are a class of chemical compounds that have shown promise in preclinical and clinical cancer settings. However, retinoids are limited by their toxicity and resistance to treatment. To overcome this resistance, various synthetic retinoids have been developed, including the adamantyl retinoid ST1926, which is a potent anti-cancer agent. However, due to its limited bioavailability, the development of ST1926 has been restricted in phase I clinical trials. We have previously investigated the preclinical efficacy of ST1926 in CRC models. ST1926 displayed potent inhibitory and apoptotic effects in CRC cell lines by inducing early DNA damage and apoptosis. ST1926 significantly reduced the tumor doubling time and tumor burden in a xenograft CRC model. Therefore, we developed ST1926-NPs and assessed their efficacy in CRC models. ST1926-NPs were produced using Flash NanoPrecipitation with the amphiphilic diblock copolymer polystyrene-b-ethylene oxide and cholesterol as a co-stabilizer. ST1926 was formulated into NPs with a drug to polymer mass ratio of 1:2, providing a stable formulation for one week. The contin ST1926-NP diameter was 100 nm, with a polydispersity index of 0.245. Using the MTT cell viability assay, ST1926-NP exhibited potent anti-growth activities as naked ST1926 in HCT116 cells, at pharmacologically achievable concentrations. Future studies will be performed to study the anti-tumor activities and mechanism of action of ST1926-NPs in a xenograft mouse model and to detect the compound and its glucuroconjugated form in the plasma of mice. Ultimately, our studies will support the use of ST1926-NP formulations in enhancing the stability and bioavailability of ST1926 in CRC.

Keywords: nanoparticles, drug delivery, colorectal cancer, retinoids

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Authors: Leah Ning

Abstract:

This paper discusses the development of a machine learning algorithm that accurately detects metastatic breast cancer (cancer has spread elsewhere from its origin part) in selected images that come from pathology scans of lymph node sections. Being able to develop an accurate artificial intelligence (AI) algorithm would help significantly in breast cancer diagnosis since manual examination of lymph node scans is both tedious and oftentimes highly subjective. The usage of AI in the diagnosis process provides a much more straightforward, reliable, and efficient method for medical professionals and would enable faster diagnosis and, therefore, more immediate treatment. The overall approach used was to train a convolution neural network (CNN) based on a set of pathology scan data and use the trained model to binarily classify if a new scan were benign or malignant, outputting a 0 or a 1, respectively. The final model’s prediction accuracy is very high, with 100% for the train set and over 70% for the test set. Being able to have such high accuracy using an AI model is monumental in regard to medical pathology and cancer detection. Having AI as a new tool capable of quick detection will significantly help medical professionals and patients suffering from cancer.

Keywords: breast cancer detection, AI, machine learning, algorithm

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Authors: Sarpong Boateng, Rohit Balasundaram, Akua Afrah Amoah

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Introduction: Racial and Gender disparities have been found to be independently associated with Salivary Gland Cancers (SGCs) survival; however, to our best knowledge, there are no previous studies on the interplay of these social determinants on the prognosis of SGCs. The objective of this study was to examine the joint effect of race and gender on the survival of SGCs. Methods: We analyzed survival outcomes of 13,547 histologically confirmed cases of SGCs using the Surveillance Epidemiology and End Results (SEER) database (2004 to 2015). Multivariable Cox regression analysis and Kaplan-Meier curves were used to estimate hazard ratios (HR) after controlling for age, tumor characteristics, treatment type and year of diagnosis. Results: 73.5% of the participants were whites, 8.5% were blacks, 10.1% were Hispanics and 58.5% were males. Overall, males had poorer survival than females (HR = 1.16, p=0.003). In the adjusted multivariable model, there were no significant differences in survival by race. However, the interaction of gender and race was statistically significant (p=0.01) in Hispanic males. Thus, compared to White females (reference), Hispanic females had significantly better survival (HR=0.53), whiles Hispanic males had worse survival outcomes (HR=1.82) for SGCs. Conclusions: Our results show significant interactions between race and gender, with racial disparities varying across the different genders for SGCs survival. This study indicates that racial and gender differences are crucial factors to be considered in the prognostic counseling and management of patients with SGCs. Biologic factors, tumor genetic characteristics, chemotherapy, lifestyle, environmental exposures, and socioeconomic and dietary factors are potential yet proven reasons that could account for racial and gender differences in the survival of SGCs.

Keywords: salivary, cancer, survival, disparity, race, gender, SEER

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Authors: Farhan Sohail, Gul Shahnaz Irshad Hussain, Shoaib Sarwar, Ibrahim Javed, Zajif Hussain, Akhtar Nadhman

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The present study was aimed to develop a hybrid nanocarrier (NC) system with enhanced membrane permeability, bioavailability and targeted delivery of Docetaxel (DTX) in breast cancer. Hybrid NC’s based on folic acid (FA) grafted thiolated chitosan (TCS) enveloped liposomes were prepared with DTX and evaluated in-vitro and in-vivo for their enhanced permeability and bioavailability. Physicochemical characterization of NC’s including particle size, morphology, zeta potential, FTIR, DSC, PXRD, encapsulation efficiency and drug release from NC’s was determined in vitro. Permeation enhancement and p-gp inhibition were performed through everted sac method on freshly excised rat intestine which indicated that permeation was enhanced 5 times as compared to pure DTX and the hybrid NC’s were strongly able to inhibit the p-gp activity as well. In-vitro cytotoxicity and tumor targeting was done using MDA-MB-231 cell line. The stability study of the formulations performed for 3 months showed the improved stability of FA-TCS enveloped liposomes in terms of its particles size, zeta potential and encapsulation efficiency as compared to TCS NP’s and liposomes. The pharmacokinetic study was performed in vivo using rabbits. The oral bioavailability and AUC0-96 was increased 10.07 folds with hybrid NC’s as compared to positive control. Half-life (t1/2) was increased 4 times (58.76 hrs) as compared to positive control (17.72 hrs). Conclusively, it is suggested that FA-TCS enveloped liposomes have strong potential to enhance permeability and bioavailability of hydrophobic drugs after oral administration and tumor targeting.

Keywords: docetaxel, coated liposome, permeation enhancement, oral bioavailability

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Authors: Mojtaba Barzegar, Alireza Shirazi, Saied Rabi Mahdavi

Abstract:

Intraoperative radiation therapy (IORT) is an innovative treatment modality that the delivery of a large single dose of radiation to the tumor bed during the surgery. The radiotherapy success depends on the absorbed dose delivered to the tumor. The achievement better accuracy in patient treatment depends upon the measured dose by standard dosimeter such as ionization chamber, but because of the high density of electric charge/pulse produced by the accelerator in the ionization chamber volume, the standard correction factor for ion recombination Ksat calculated with the classic two-voltage method is overestimated so the use of dose/pulse independent dosimeters such as chemical Fricke and ethanol chlorobenzene (ECB) dosimeters have been suggested. Dose measurement is usually calculated and calibrated in the Zmax. Ksat calculated by comparison of ion chamber response and ECB dosimeter at each applicator degree, size, and dose. The relative output factors for IORT applicators have been calculated and compared with experimentally determined values and the results simulated by Monte Carlo software. The absorbed doses have been calculated and measured with statistical uncertainties less than 0.7% and 2.5% consecutively. The relative differences between calculated and measured OF’s were up to 2.5%, for major OF’s the agreement was better. In these conditions, together with the relative absorbed dose calculations, the OF’s could be considered as an indication that the IORT electron beams have been well simulated. These investigations demonstrate the utility of the full Monte Carlo simulation of accelerator head with ECB dosimeter allow us to obtain detailed information of clinical IORT beams.

Keywords: intra operative radiotherapy, ethanol chlorobenzene, ksat, output factor, monte carlo simulation

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Authors: Sarah Crawford, Gerry Lesley

Abstract:

This research is a pre-clinical assessment of anti-cancer effects of novel non-steroidal diethyl stilbestrol-like estrogen analogs in estrogen-receptor positive/ progesterone-receptor positive human breast cancer microtumors of MCF 7 cell line. Tamoxifen analog formulation (Tam A1) was used as a single agent or in combination with therapeutic concentrations of 4-hydroxytamoxifen, currently used as a long-term treatment for the prevention of breast cancer recurrence in women with estrogen receptor positive/ progesterone receptor positive malignancies. At concentrations ranging from 30-50 microM, Tam A1 induced microtumor disaggregation and cell death. Incremental cytotoxic effects correlated with increasing concentrations of Tam A1. Live tumor microscopy showed that microtumos displayed diffuse borders and substrate-attached cells were rounded-up and poorly adherent. A complete cytotoxic effect was observed using 40-50 microM Tam A1 with time course kinetics similar to 4-hydroxytamoxifen. Combined treatment with TamA1 (30-50 microM) and 4-hydroxytamoxifen (10-15 microM) induced a highly cytotoxic, synergistic combined treatment response that was more rapid and complete than using 4-hydroxytamoxifen as a single agent therapeutic. Microtumors completely dispersed or formed necrotic foci indicating a highly cytotoxic combined treatment response. Moreover, breast cancer microtumors treated with both 4-hydroxytamoxifen and Tam A1 displayed lower levels of long-term post-treatment regrowth, a critical parameter of primary drug resistance, than observed for 4-hydroxytamoxifen when used as a single agent therapeutic. Tumor regrowth at 6 weeks post-treatment with either single agent 4-hydroxy tamoxifen, Tam A1 or a combined treatment was assessed for the development of drug resistance. Breast cancer cells treated with both 4-hydroxytamoxifen and Tam A1 displayed significantly lower levels of post-treatment regrowth, indicative of decreased drug resistance, than observed for either single treatment modality. The preclinical data suggest that combined treatment involving the use of tamoxifen analogs may be a novel clinical approach for long-term maintenance therapy in patients with estrogen-receptor positive/progesterone-receptor positive breast cancer receiving hormonal therapy to prevent disease recurrence. Detailed data on time-course, IC50 and tumor regrowth assays post- treatment as well as a proposed mechanism of action to account for observed synergistic drug effects will be presented.

Keywords: 4-hydroxytamoxifen, tamoxifen analog, drug-resistance, microtumors

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Authors: I. Stathopoulos, V. Syrgiamiotis, E. Karavasilis, A. Ploussi, I. Nikas, C. Hatzigiorgi, K. Platoni, E. P. Efstathopoulos

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Introduction: Brain and central nervous system (CNS) tumors form the second most common group of cancer in children, accounting for 30% of all childhood cancers. MRI is the key imaging technique used for the visualization and management of pediatric brain tumors. Initial characterization of tumors from MRI scans is usually performed via a radiologist’s visual assessment. However, different brain tumor types do not always demonstrate clear differences in visual appearance. Using only conventional MRI to provide a definite diagnosis could potentially lead to inaccurate results, and so histopathological examination of biopsy samples is currently considered to be the gold standard for obtaining definite diagnoses. Machine learning is defined as the study of computational algorithms that can use, complex or not, mathematical relationships and patterns from empirical and scientific data to make reliable decisions. Concerning the above, machine learning techniques could provide effective and accurate ways to automate and speed up the analysis and diagnosis for medical images. Machine learning applications in radiology are or could potentially be useful in practice for medical image segmentation and registration, computer-aided detection and diagnosis systems for CT, MR or radiography images and functional MR (fMRI) images for brain activity analysis and neurological disease diagnosis. Purpose: The objective of this study is to provide an automated tool, which may assist in the imaging evaluation and classification of brain neoplasms in pediatric patients by determining the glioma type, grade and differentiating between different brain tissue types. Moreover, a future purpose is to present an alternative way of quick and accurate diagnosis in order to save time and resources in the daily medical workflow. Materials and Methods: A cohort, of 80 pediatric patients with a diagnosis of posterior fossa tumor, was used: 20 ependymomas, 20 astrocytomas, 20 medulloblastomas and 20 healthy children. The MR sequences used, for every single patient, were the following: axial T1-weighted (T1), axial T2-weighted (T2), FluidAttenuated Inversion Recovery (FLAIR), axial diffusion weighted images (DWI), axial contrast-enhanced T1-weighted (T1ce). From every sequence only a principal slice was used that manually traced by two expert radiologists. Image acquisition was carried out on a GE HDxt 1.5-T scanner. The images were preprocessed following a number of steps including noise reduction, bias-field correction, thresholding, coregistration of all sequences (T1, T2, T1ce, FLAIR, DWI), skull stripping, and histogram matching. A large number of features for investigation were chosen, which included age, tumor shape characteristics, image intensity characteristics and texture features. After selecting the features for achieving the highest accuracy using the least number of variables, four machine learning classification algorithms were used: k-Nearest Neighbour, Support-Vector Machines, C4.5 Decision Tree and Convolutional Neural Network. The machine learning schemes and the image analysis are implemented in the WEKA platform and MatLab platform respectively. Results-Conclusions: The results and the accuracy of images classification for each type of glioma by the four different algorithms are still on process.

Keywords: image classification, machine learning algorithms, pediatric MRI, pediatric oncology

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Authors: Rasha Ahmadi

Abstract:

Glioblastoma is one of the most frequent brain malignancies, having a high mortality rate and limited survival in individuals with this malignancy. Despite different treatments and surgery, recurrence of glioblastoma cancer stem cells may arise as a subsequent tumor. For this reason, it is crucial to research the markers associated with glioblastoma stem cells and specifically their microenvironment. In this study, using bioinformatics analysis, we analyzed and nominated genes in the microenvironment pathways of glioblastoma stem cells. In this study, an appropriate database was selected for analysis by referring to the GEO database. This dataset comprised gene expression patterns in stem cells derived from glioblastoma patients. Gene clusters were divided as high and low expression. Enrichment databases such as Enrichr, STRING, and GEPIA were utilized to analyze the data appropriately. Finally, we extracted the potential genes 2700 high-expression and 1100 low-expression genes are implicated in the metabolic pathways of glioblastoma cancer progression. Cellular senescence, MAPK, TNF, hypoxia, zimosterol biosynthesis, and phosphatidylinositol metabolism pathways were substantially expressed and the metabolic pathways were downregulated. After assessing the association between protein networks, MSMP, SOX2, FGD4 ,and CNTNAP3 genes with high expression and DMKN and SBSN genes with low were selected. All of these genes were observed in the survival curve, with a survival of fewer than 10 percent over around 15 months. hsa-mir-192-5p, hsa-mir-129-5p, hsa-mir-215-5p, hsa-mir-335-5p, and hsa-mir-340-5p played key function in glioblastoma cancer stem cells microenviroments. We introduced critical genes through integrated and regular bioinformatics studies by assessing the amount of gene expression profile data that can play an important role in targeting genes involved in the energy and microenvironment of glioblastoma cancer stem cells. Have. This study indicated that hsa-mir-192-5p, and hsa-mir-129-5p are appropriate candidates for this.

Keywords: Glioblastoma, Cancer Stem Cells, Biomarker Discovery, Gene Expression Profiles, Bioinformatics Analysis, Tumor Microenvironment

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Authors: Sumera, Sanila Amber, Fatima Javed Mirza, Amjad Ali, Saadia Zahid

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Glioblastoma multiforme (GBM) is a widely spread and fatal primary brain tumor with an increased risk of relapse in spite of aggressive treatment. The current procedures for GBM diagnosis include invasive procedures i.e. resection or biopsy, to acquire tumor mass. Implementation of negligibly invasive tests as a potential diagnostic technique and biofluid-based monitoring of GBM stresses on discovering biomarkers in CSF and blood. Therefore, we performed a comprehensive in silico analysis to identify potential circulating biomarkers for GBM. Initially, six gene and protein databases were utilized to mine brain-specific proteins. The resulting proteins were filtered using a channel of five tools to predict the secretory proteins. Subsequently, the expression profile of the secreted proteins was verified in the brain and blood using two databases. Additional verification of the resulting proteins was done using Plasma Proteome Database (PPD) to confirm their presence in blood. The final set of proteins was searched in literature for their relationship with GBM, keeping a special emphasis on secretome proteome. 2145 proteins were firstly mined as brain-specific, out of which 69 proteins were identified as secretory in nature. Verification of expression profile in brain and blood eliminated 58 proteins from the 69 proteins, providing a final list of 11 proteins. Further verification of these 11 proteins further eliminated 2 proteins, giving a final set of nine secretory proteins i.e. OPCML, NPTX1, LGI1, CNTN2, LY6H, SLIT1, CREG2, GDF1 and SERPINI1. Out of these 9 proteins, 7 were found to be linked to GBM, whereas 2 proteins are not investigated in GBM so far. We propose that these secretory proteins can serve as potential circulating biomarker signatures of GBM and will facilitate the development of minimally invasive diagnostic methods and novel therapeutic interventions for GBM.

Keywords: glioblastoma multiforme, secretory proteins, brain secretome, biomarkers

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Authors: Abdoulie K. Ceesay

Abstract:

Within the sequence of the whole genome, it is known that 99.9% of the human genome is similar, whilst our difference lies in just 0.1%. Among these minor dissimilarities, the most common type of genetic variations that occurs in a population is SNP, which arises due to nucleotide substitution in a protein sequence that leads to protein destabilization, alteration in dynamics, and other physio-chemical properties’ distortions. While causing variations, they are equally responsible for our difference in the way we respond to a treatment or a disease, including various cancer types. There are two types of SNPs; synonymous single nucleotide polymorphism (sSNP) and non-synonymous single nucleotide polymorphism (nsSNP). sSNP occur in the gene coding region without causing a change in the encoded amino acid, while nsSNP is deleterious due to its replacement of a nucleotide residue in the gene sequence that results in a change in the encoded amino acid. Predicting the effects of cancer related nsSNPs on protein stability, function, and dynamics is important due to the significance of phenotype-genotype association of cancer. In this thesis, Data of 5 oncogenes (ONGs) (AKT1, ALK, ERBB2, KRAS, BRAF) and 5 tumor suppressor genes (TSGs) (ESR1, CASP8, TET2, PALB2, PTEN) were retrieved from ClinVar. Five common in silico tools; Polyphen, Provean, Mutation Assessor, Suspect, and FATHMM, were used to predict and categorize nsSNPs as deleterious, benign, or neutral. To understand the impact of each variation on the phenotype, Maestro, PremPS, Cupsat, and mCSM-NA in silico structural prediction tools were used. This study comprises of in-depth analysis of 10 cancer gene variants downloaded from Clinvar. Various analysis of the genes was conducted to derive a meaningful conclusion from the data. Research done indicated that pathogenic variants are more common among ONGs. Our research also shows that pathogenic and destabilizing variants are more common among ONGs than TSGs. Moreover, our data indicated that ALK(409) and BRAF(86) has higher benign count among ONGs; whilst among TSGs, PALB2(1308) and PTEN(318) genes have higher benign counts. Looking at the individual cancer genes predisposition or frequencies of causing cancer according to our research data, KRAS(76%), BRAF(55%), and ERBB2(36%) among ONGs; and PTEN(29%) and ESR1(17%) among TSGs have higher tendencies of causing cancer. Obtained results can shed light to the future research in order to pave new frontiers in cancer therapies.

Keywords: tumor suppressor genes (TSGs), oncogenes (ONGs), non synonymous single nucleotide polymorphism (nsSNP), single nucleotide polymorphism (SNP)

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Authors: E. Locatelli, I. Monaco, R. C. Martin, Y. Li, R. Pini, M. Chiariello, M. Comes Franchini

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Despite the many advantages of application of nanomaterials in the field of nanomedicine, increasing concerns have been expressed on their potential adverse effects on human health. There is urgency for novel green strategies toward novel materials with enhanced biocompatibility using safe reagents. Photothermal ablation therapy, which exploits localized heat increase of a few degrees to kill cancer cells, has appeared recently as a non-invasive and highly efficient therapy against various cancer types; anyway new agents able to generate hyperthermia when irradiated are needed and must have precise biocompatibility in order to avoid damage to healthy tissues and prevent toxicity. Recently, there has been increasing interest in magnesium as a biomaterial: it is the fourth most abundant cation in the human body, and it is essential for human metabolism. However magnesium nanoparticles (Mg NPs) have had limited diffusion due to the high reduction potential of magnesium cations, which makes NPs synthesis challenging. Herein, we report the synthesis of Mg NPs and their surface functionalization for the obtainment of a stable and biocompatible nanomaterial suitable for photothermal ablation therapy against cancer. We synthesized the Mg crystals by reducing MgCl2 with metallic lithium and exploiting naphthalene as an electron carrier: the lithium–naphthalene complex acts as the real reducing agent. Firstly, the nanocrystal particles were coated with the ligand 12-ethoxy ester dodecanehydroxamic acid, and then entrapped into water-dispersible polymeric micelles (PMs) made of the FDA-approved PLGA-b-PEG-COOH copolymer using the oil-in-water emulsion technique. Lately, we developed a more straightforward methodology by introducing chitosan, a highly biocompatible natural product, at the beginning of the process, simultaneously using lithium–naphthalene complex, thus having a one-pot procedure for the formation and surface modification of MgNPs. The obtained MgNPs were purified and fully characterized, showing diameters in the range of 50-300 nm. Notably, when coated with chitosan the particles remained stable as dry powder for more than 10 months. We proved the possibility of generating a temperature rise of a few to several degrees once MgNPs were illuminated using a 810 nm diode laser operating in continuous wave mode: the temperature rise resulted significant (0-15 °C) and concentration dependent. We then investigated potential cytotoxicity of the MgNPs: we used HN13 epithelial cells, derived from a head and neck squamous cell carcinoma and the hepa1-6 cell line, derived from hepatocellular carcinoma and very low toxicity was observed for both nanosystems. Finally, in vivo photothermal therapy was performed on xenograft hepa1-6 tumor bearing mice: the animals were treated with MgNPs coated with chitosan and showed no sign of suffering after the injection. After 12 hours the tumor was exposed to near-infrared laser light. The results clearly showed an extensive damage to tumor tissue after only 2 minutes of laser irradiation at 3Wcm-1, while no damage was reported when the tumor was treated with the laser and saline alone in control group. Despite the lower photothermal efficiency of Mg with respect to Au NPs, we consider MgNPs a promising, safe and green candidate for future clinical translations.

Keywords: chitosan, magnesium nanoparticles, nanomedicine, photothermal therapy

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Authors: Marta E. Hernandez-Caballero, Veronica Borgonio-Cuadra, Antonio Miranda-Duarte, Xochitl Rojas-Toledo, Normand Garcia-Hernandez, Maura Cardenas-Garcia, Teresa Abad-Camacho

Abstract:

Breast cancer (BC) is the most common tumor in women over the world. DNA methylation is an epigenetic modification critical in CpG sites, aberrant methylation of CpG islands in promoters is a hallmark of cancer. So, gene expression can be regulated by alterations in DNA methylation. In cell lines DACT2 gene reduces the growth and migration of tumor cells by its participation in the suppression of TGFb/SMAD2/3. PHF20L1 is involved in histone acetylation therefore, it regulates transcription. Our aim was to analyze the methylation status of the DACT2 and PHF20L1 promoter regions in tumoral and healthy mammary tissue from women with BC in different progression states. The study included 77 patients from Centro Medico Nacional La Raza in Mexico City. After identifying a CpG island in DACT2 and PHF20L1 promoters, DNA methylation status was analyzed through sodium bisulfite with subsequent amplification using methylation-specific PCR. Results revealed no changes in methylation status of PHF20L1 and cancer stages (II y III) or in comparison to healthy tissues, it was demethylated. DACT2 promoter methylation was no significant between tumoral stages (II, P = 0.37; III, P = 0.17) or with healthy tissue. Previous data reported DACT2 methylated in nasopharyngeal carcinoma but in this study promoter methylation was not observed. PHF20L1 protein contains N-terminal Tudor and C-terminal plant homeodomain domains, it has been suggested that can stabilize DNMT1 regulating DNA methylation, therefore, was associated with poor prognostic in BC. We found no evidence of methylation in patients and controls in PHF20L1 promoter, so its association with BC may have no direct relation with promoter methylation. More studies including other methylation sites in these genes in BC are necessary.

Keywords: bisulfite conversion, breast cancer, DACT2, DNA methylation, PHF20L1, tumoral status

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Authors: Hasan Frookh Jamal

Abstract:

This is a case of a 36-year-old Bahraini gentleman diagnosed to have Cushing's Syndrome with a large anterior mediastinal mass. He was sent abroad to the Speciality hospital in Jordan, where he underwent diagnostic video-assisted thoracoscopy, partial thymectomy and pericardial fat excision. Histopathology of the mass was reported to be an Atypical carcinoid tumor with a low Ki67 proliferation index of 5%, the mitotic activity of 4 MF/10HPF and pathological stage classification(pTNM): pT1aN1. MRI of the pituitary gland showed an ill-defined non-enhancing focus of about 3mm on the Rt side of the pituitary on coronal images, with a similar but smaller one on the left side, which could be due to enhancing pattern rather than a real lesion as reported. The patient underwent Ga68 Dotate PET/CT scan post-operatively, which showed multiple somatostatin receptor-positive lesions seen within the tail, body and head of the pancreas and positive somatostatin receptor lymph nodes located between the pancreatic head and IVC. There was no uptake detected at the anterior mediastinum nor at the site of thymic mass resection. There was no evidence of any positive somatostatin uptake at the soft tissue or lymph nodes. The patient underwent IPSS, which proved that the source is, in fact, an ectopic source of ACTH secretion. Unfortunately, the patient's serum cortisol remained elevated after surgery and failed to be suppressed by 1 mg ODST and by 2 days LLDST with a high ACTH value. The patient was started on Osilodrostat for treatment of hypercortisolism for the time being and his future treatment plan with Lutetium-177 Dotate therapy vs. bilateral adrenalectomy is to be considered in an MDT meeting.

Keywords: cushing syndrome, neuroendocrine tumur, carcinoid tumor, Thymoma

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Authors: Sadeem Aljamaan, Reem Hariri, Rahaf Alghamdi, Batool Alotaibi, Batool Alsenan, Lama Althunayyan, Areej Alnemer

Abstract:

The aim of this study is to correlate between radiological findings and histopathological results in regard to the breast imaging-reporting and data system scores, size of breast masses, molecular subtypes and suspicious radiological features, as well as to assess the concordance rate in histological grade between core biopsy and surgical excision among breast cancer patients, followed by analyzing the change of concordance rate in relation to neoadjuvant chemotherapy in a Saudi population. A retrospective review was conducted over 6-year period (2017-2022) on all breast core biopsies of women preceded by radiological investigation. Chi-squared test (χ2) was performed on qualitative data, the Mann-Whitney test for quantitative non-parametric variables, and the Kappa test for grade agreement. A total of 641 cases were included. Ultrasound, mammography, and magnetic resonance imaging demonstrated diagnostic accuracies of 85%, 77.9% and 86.9%; respectively. magnetic resonance imaging manifested the highest sensitivity (72.2%), and the lowest was for ultrasound (61%). Concordance in tumor size with final excisions was best in magnetic resonance imaging, while mammography demonstrated a higher tendency of overestimation (41.9%), and ultrasound showed the highest underestimation (67.7%). The association between basal-like molecular subtypes and the breast imaging-reporting and data system score 5 classifications was statistically significant only for magnetic resonance imaging (p=0.04). Luminal subtypes demonstrated a significantly higher percentage of speculation in mammography. Breast imaging-reporting and data system score 4 manifested a substantial number of benign pathologies in all the 3 modalities. A fair concordance rate (k= 0.212 & 0.379) was demonstrated between excision and the preceding core biopsy grading with and without neoadjuvant therapy, respectively. The results demonstrated a down-grading in cases post-neoadjuvant therapy. In cases who did not receive neoadjuvant therapy, underestimation of tumor grade in biopsy was evident. In summary, magnetic resonance imaging had the highest sensitivity, specificity, positive predictive value and accuracy of both diagnosis and estimation of tumor size. Mammography demonstrated better sensitivity than ultrasound and had the highest negative predictive value, but ultrasound had better specificity, positive predictive value and accuracy. Therefore, the combination of different modalities is advantageous. The concordance rate of core biopsy grading with excision was not impacted by neoadjuvant therapy.

Keywords: breast cancer, mammography, MRI, neoadjuvant, pathology, US

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Authors: M. R. Akbari, M. Sadeghi, R. Faghihi, M. A. Mosleh-Shirazi, A. R. Khorrami-Moghadam

Abstract:

Proton radiotherapy (PRT) is becoming an established treatment modality for cancer. The localized tumors, the same as undifferentiated thyroid tumors are insufficiently handled by conventional radiotherapy, while protons would propose the prospect of increasing the tumor dose without exceeding the tolerance of the surrounding healthy tissues. In spite of relatively high advantages in giving localized radiation dose to the tumor region, in proton therapy, secondary neutron production can have significant contribution on integral dose and lessen advantages of this modality contrast to conventional radiotherapy techniques. Furthermore, neutrons have high quality factor, therefore, even a small physical dose can cause considerable biological effects. Measuring of this neutron dose is a very critical step in prediction of secondary cancer incidence. It has been found that FLUKA Monte Carlo code simulations have been used to evaluate dose due to secondaries in proton therapy. In this study, first, by validating simulated proton beam range in water phantom with CSDA range from NIST for the studied proton energy range (34-54 MeV), a proton therapy in thyroid gland cancer was simulated using FLUKA code. Secondary neutron dose equivalent of some organs and tissues after the target volume caused by 34 and 54 MeV proton interactions were calculated in order to evaluate secondary cancer incidence. A multilayer cylindrical neck phantom considering all the layers of neck tissues and a proton beam impinging normally on the phantom were also simulated. Trachea (accompanied by Larynx) had the greatest dose equivalent (1.24×10-1 and 1.45 pSv per primary 34 and 54 MeV protons, respectively) among the simulated tissues after the target volume in the neck region.

Keywords: FLUKA code, neutron dose equivalent, proton therapy, thyroid gland

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