Search results for: malignant tumors

Authors: Meryem Saban Guler, Saniye Bilici

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Malnutrition is a problem that significantly affects patients with cancer throughout the course of their illness, and it may be present from the moment of diagnosis until the end of treatment. We searched electronic databases using key terms such as ‘malnutrition in cancer patients’ or ‘nutritional status in cancer’ or ‘nutritional screening tools’ etc. Decline in nutritional status and continuing weight loss are associated with an increase in number and severity of complications, impaired quality of life and decreased survival rate. Nutrition is an important factor in the treatment and progression of cancer. Cancer patients are particularly susceptible to nutritional depletion due to the combined effects of the malignant disease and its treatment. With increasing incidence of cancer, identification and management of nutritional deficiencies are needed. Early identification of malnutrition, is substantial to minimize or prevent undesirable outcomes throughout clinical course. In determining the nutritional status; food consumption status, anthropometric methods, laboratory tests, clinical symptoms, psychosocial data are used. First-line strategies must include routine screening and identification of inpatients or outpatients at nutritional risk with the use of a simple and standardized screening tool. There is agreement among international nutrition organizations and accredited health care organizations that routine nutritional screening should be a standard procedure for every patient admitted to a hospital. There are f management of all cancer patients therefore routine nutritional screening with validated tools can identify cancer patients at risk.

Keywords: cancer, malnutrition, nutrition, nutritional screening

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

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

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

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Authors: Ahmed Ashit

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Image fusion is a significant and efficient image processing method used for detecting different types of tumors. This method has been used as an effective combination technique for obtaining high quality images that combine anatomy and physiology of an organ. It is the main key in the huge biomedical machines for diagnosing cancer such as PET-CT machine. This thesis aims to develop an image analysis system for the detection of the eye tumor. Different image processing methods are used to extract the tumor and then mark it on the original image. The images are first smoothed using median filtering. The background of the image is subtracted, to be then added to the original, results in a brighter area of interest or tumor area. The images are adjusted in order to increase the intensity of their pixels which lead to clearer and brighter images. once the images are enhanced, the edges of the images are detected using canny operators results in a segmented image comprises only of the pupil and the tumor for the abnormal images, and the pupil only for the normal images that have no tumor. The images of normal and abnormal images are collected from two sources: “Miles Research” and “Eye Cancer”. The computerized experimental results show that the developed image fusion based eye tumor detection system is capable of detecting the eye tumor and segment it to be superimposed on the original image.

Keywords: image fusion, eye tumor, canny operators, superimposed

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Authors: Thampi Rawther, Sean O’Brien, Kamala Kanta Das

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Background: Intussusception in the adult is rarely from a benign cause and is almost always pathological. Causes include carcinomas, polyps, Meckel's diverticulum, or colonic diverticulum. Common symptoms include abdominal pain, intestinal obstruction, palpable abdominal mass, GI bleeding, and anemia. Sarcomatoid carcinoma is a rare type of small intestinal malignancy exhibiting carcinomatous and sarcomatous features. It primarily affects older patients, mean age 57, and is 1.5 times more prevalent in men. Method: This is an interesting case report of a patient presenting with intussusception secondary to a sarcomatoid tumor of the small bowel. Conclusion: Surgery is the treatment of choice in adults with intussusception due to the high malignancy potential. Furthermore, surgical resection of the affected bowel is the definitive form of therapy as small bowel sarcomatoid tumors are not responsive to chemotherapy and radiotherapy. Early surgical intervention helps reduce mortality as it allows for early staging, treatment, and monitoring of the tumor. The patient was fortunate to have presented with intussusception, facilitating early surgical intervention, and was found to have a low disease stage.

Keywords: general surgery, small bowel tumour, imaging, unique

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

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Dosimetry is an indispensable and precious factor in patient treatment planning; to minimize the absorbed dose in vital tissues. In this study, In accordance with the proper characteristics of DOTATOC and ¹⁷⁷Lu, after preparing ¹⁷⁷Lu-DOTATOC at the optimal conditions for the first time in Iran, radionuclidic and radiochemical purity of the solution was investigated using an HPGe spectrometer and ITLC method, respectively. The biodistribution of the compound was assayed for treatment of adenocarcinoma breast cancer in bearing BALB/c mice. The results have demonstrated that ¹⁷⁷Lu-DOTATOC is a profitable selection for therapy of the tumors. Because of the vital role of internal dosimetry before and during therapy, the effort to improve the accuracy and rapidity of dosimetric calculations is necessary. For this reason, a new method was accomplished to calculate the absorbed dose through mixing between compartmental model, animal dosimetry and extrapolated data from animal to human and using MIRD method. Despite utilization of compartmental model based on the experimental data, it seems this approach may increase the accuracy of dosimetric data, confidently.

Keywords: ¹⁷⁷Lu-DOTATOC, biodistribution modeling, compartmental model, internal dosimetry

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Authors: Ahmed Mostafa, Mohamed Mahmoud, Nesreen H. Hafez, Mohamed Fahim

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This retrospective study includes 60 patients with pre-invasive breast cancer. Aim of the study: Evaluation of premalignant lesions of the breast (DCIS), different treatment methods and outcome. Patients and methods: 60 patients with DCIS were studied from the period between 2005 to 2012, for 38 patients the primary surgical method was wide local resection (WLE) (63.3%) and the other cases (22 patients, 36.7%) had mastectomy, fourteen cases from those who underwent local excision received radiotherapy, while no adjuvant radiotherapy was given for those who underwent mastectomy. In case of hormonal receptor positive DCIS lesions hormonal treatment (Tamoxifen) was given after local control. Results: No difference in overall survival between mastectomy & breast conserving therapy (wide local excision and adjuvant radiotherapy), however local recurrence rate is higher in case of breast conserving therapy, also no role of Axillary evacuation in case of DCIS. The use of hormonal therapy decreases the incidence of local recurrence by about 98%. Conclusion: The main management of DCIS is local treatment (wide local excision and radiotherapy) with hormonal treatment in case of hormone receptor positive lesions.

Keywords: ductal carcinoma in situ, surgical treatment, radiotherapy, breast conserving therapy, hormonal treatment

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Authors: Manuel I. Capel, Antonio Tomeu, Alberto Salguero

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Tumor growth from a transformed cancer-cell up to a clinically apparent mass spans through a range of spatial and temporal magnitudes. Through computer simulations, Cellular Automata (CA) can accurately describe the complexity of the development of tumors. Tumor development prognosis can now be made -without making patients undergo through annoying medical examinations or painful invasive procedures- if we develop appropriate CA-based software tools. In silico testing mainly refers to Computational Biology research studies of application to clinical actions in Medicine. To establish sound computer-based models of cellular behavior, certainly reduces costs and saves precious time with respect to carrying out experiments in vitro at labs or in vivo with living cells and organisms. These aim to produce scientifically relevant results compared to traditional in vitro testing, which is slow, expensive, and does not generally have acceptable reproducibility under the same conditions. For speeding up computer simulations of cellular models, specific literature shows recent proposals based on the CA approach that include advanced techniques, such the clever use of supporting efficient data structures when modeling with deterministic stochastic cellular automata. Multiparadigm and multiscale simulation of tumor dynamics is just beginning to be developed by the concerned research community. The use of stochastic cellular automata (SCA), whose parallel programming implementations are open to yield a high computational performance, are of much interest to be explored up to their computational limits. There have been some approaches based on optimizations to advance in multiparadigm models of tumor growth, which mainly pursuit to improve performance of these models through efficient memory accesses guarantee, or considering the dynamic evolution of the memory space (grids, trees,…) that holds crucial data in simulations. In our opinion, the different optimizations mentioned above are not decisive enough to achieve the high performance computing power that cell-behavior simulation programs actually need. The possibility of using multicore and GPU parallelism as a promising multiplatform and framework to develop new programming techniques to speed-up the computation time of simulations is just starting to be explored in the few last years. This paper presents a model that incorporates parallel processing, identifying the synchronization necessary for speeding up tumor growth simulations implemented in Java and C++ programming environments. The speed up improvement that specific parallel syntactic constructs, such as executors (thread pools) in Java, are studied. The new tumor growth parallel model is proved using implementations with Java and C++ languages on two different platforms: chipset Intel core i-X and a HPC cluster of processors at our university. The parallelization of Polesczuk and Enderling model (normally used by researchers in mathematical oncology) proposed here is analyzed with respect to performance gain. We intend to apply the model and overall parallelization technique presented here to solid tumors of specific affiliation such as prostate, breast, or colon. Our final objective is to set up a multiparadigm model capable of modelling angiogenesis, or the growth inhibition induced by chemotaxis, as well as the effect of therapies based on the presence of cytotoxic/cytostatic drugs.

Keywords: cellular automaton, tumor growth model, simulation, multicore and manycore programming, parallel programming, high performance computing, speed up

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Authors: Ahmad Shah Farhat

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Background: Prenatal asphyxia or birth asphyxia is the medical situation resulting from a newborn infant that lasts long enough during the birth process to cause physical harm, usually to the brain. Human umbilical cord blood (UCB) is a well-established source of hematopoietic stem/progenitor cells (HSPCs) for allogeneic stem cell transplantation. These can be used clinically to care for children with malignant diseases. Low O2 can cause in proliferation and differentiation of stem cells. Method: the cord blood of 11 infants with 3-5 Apgar scores or need to cardiac pulmonary Resuscitation as an asphyxia group and ten normal infants with more than 8 Apgar scores as the normal group was collected, and after isolating hematopoietic stem cells, the cells were cultured in enriched media for 14 days to compare the numbers of colonies by microscope. Results: There was a significant difference in the number of RBC precursor colonies (red colonies) in cultured media with 107 cord blood hematopoietic stem cells of infants who were exposed to hypoxemia in two wells of palate. There was not a significant difference in the number of white cell colonies in the two groups in the two wells of the plate. Conclusion: Hypoxia in the perinatal period can cause the increase of hematopoietic stem cells of cord blood, special red precursor stem cells in vitro, like an increase of red blood cells in the body when exposed to low oxygen conditions. Thus, it will be usable.

Keywords: asphyxia, neonre, stem cell, red cell

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Authors: Wellemans Isabelle, Remmelink Myriam, Foucart Annick, Rusu Stefan, Compère Christophe

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Primary pulmonary meningioma (PPM) is a very rare tumor, and its occurrence has been reported only sporadically. Multiple PPMs are even more exceptional, and herein, we report, to the best of our knowledge, the fourth case, focusing on the clinicopathological features of the tumor. Moreover, the possible relationship between the use of progesterone–only contraceptives and the development of these neoplasms will be discussed. Case Report: We report a case of a 51-year-old female presenting three solid pulmonary nodules, with the following localizations: right upper lobe, middle lobe, and left lower lobe, described as incidental findings on computed tomography (CT) during a pre-bariatric surgery check-up. The patient revealed no drinking or smoking history. The physical exam was unremarkable except for the obesity. The lesions ranged in size between 6 and 24 mm and presented as solid nodules with lobulated contours. The largest lesion situated in the middle lobe had mild fluorodeoxyglucose (FDG) uptake on F-18 FDG positron emission tomography (PET)/CT, highly suggestive of primary lung neoplasm. For pathological assessment, video-assisted thoracoscopic middle lobectomy and wedge resection of the right upper nodule was performed. Histological examination revealed relatively well-circumscribed solid proliferation of bland meningothelial cells growing in whorls and lobular nests, presenting intranuclear pseudo-inclusions and psammoma bodies. No signs of anaplasia were observed. The meningothelial cells expressed diffusely Vimentin, focally Progesterone receptors and were negative for epithelial (cytokeratin (CK) AE1/AE3, CK7, CK20, Epithelial Membrane Antigen (EMA)), neuroendocrine markers (Synaptophysin, Chromogranin, CD56) and Estrogenic receptors. The proliferation labelling index Ki-67 was low (<5%). Metastatic meningioma was ruled out by brain and spine magnetic resonance imaging (MRI) scans. The third lesion localized in the left lower lobe was followed-up and resected three years later because of its slow but significant growth (14 mm to 16 mm), alongside two new infra centimetric lesions. Those three lesions showed a morphological and immunohistochemical profile similar to previously resected lesions. The patient was disease-free one year post-last surgery. Discussion: Although PPMs are mostly benign and slow-growing tumors with an excellent prognosis, they do not present specific radiological characteristics, and it is difficult to differentiate it from other lung tumors, histopathologic examination being essential. Aggressive behavior is associated with atypical or anaplastic features (WHO grades II–III) The etiology is still uncertain and different mechanisms have been proposed. A causal connection between sexual hormones and meningothelial proliferation has long been suspected and few studies examining progesterone only contraception and meningioma risk have all suggested an association. In line with this, our patient was treated with Levonorgestrel, a progesterone agonist, intra-uterine device (IUD). Conclusions: PPM, defined by the typical histological and immunohistochemical features of meningioma in the lungs and the absence of central nervous system lesions, is an extremely rare neoplasm, mainly solitary and associating, and indolent growth. Because of the unspecific radiologic findings, it should always be considered in the differential diagnosis of lung neoplasms. Regarding multiple PPM, only three cases are reported in the literature, and this is the first described in a woman treated by a progesterone-only IUD to the best of our knowledge.

Keywords: pulmonary meningioma, multiple meningioma, meningioma, pulmonary nodules

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Authors: Tanushree Jaitly, Shailendra Gupta, Leila Taher, Gerold Schuler, Julio Vera

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Genomics-based personalized medicine is a promising approach to fight aggressive tumors based on patient's specific tumor mutation and expression profiles. A remarkable case is, dendritic cell-based immunotherapy, in which tumor epitopes targeting patient's specific mutations are used to design a vaccine that helps in stimulating cytotoxic T cell mediated anticancer immunity. Here we present a computational pipeline for epitope-based personalized cancer vaccines using patient-specific haplotype and cancer mutation profiles. In the workflow proposed, we analyze Whole Exome Sequencing and RNA Sequencing patient data to detect patient-specific mutations and their expression level. Epitopes including the tumor mutations are computationally predicted using patient's haplotype and filtered based on their expression level, binding affinity, and immunogenicity. We calculate binding energy for each filtered major histocompatibility complex (MHC)-peptide complex using docking studies, and use this feature to select good epitope candidates further.

Keywords: cancer immunotherapy, epitope prediction, NGS data, personalized medicine

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Authors: Liu Xiaohan

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Epstein–Barr virus (EBV) is a human herpesvirus and is closely related to many malignancies of lymphocyte and epithelial origins, such as gastric cancer, Burkitt’s lymphoma, and nasopharyngeal carcinoma (NPC). NPC is a malignant epithelial tumor which is 100% associated with EBV latent infection. Most of the NPC cases are densely populated in southern China, especially in Guangdong and Hong Kong. To our knowledge, overexpression of pro-inflammatory cytokines may result in a loss of balance of the immune system and cause damage to human bodies. Interleukin-6 (IL6) is a pro-inflammatory cytokine which plays an important role in tumor progression. In addition, gene expression is regulated by both transcriptional and post-transcriptional pathways, while post-transcriptional regulation is an important mechanism to modulate the mature mRNA level in mammalian cells. AU-rich element binding factor 1 (AUF1)/heterogeneous nuclear RNP D (hnRNP D) is known for its function in destabilizing mRNAs, including cytokines and cell cycle regulators. Previous studies have found that overexpression of hnRNP D would lead to tumorigenesis. In this project, our aim is to determine the role played by hnRNP D in EBV-infected cells and how our anti-EBV agents can affect the function of hnRNP D. The results of this study will provide a new insight into how the pro-inflammatory cytokine expression can be regulated by EBV.

Keywords: interleukin 6 (IL6), epstein-barr virus (EBV), nasopharyngeal carcinoma (NPC, epstein-barr nuclear antigen-1 (EBNA1)

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Authors: Sophio Kalmakhelidze, Eka Shekiladze, Tamar Sanikidze, Mikheil Gogebashvili, Nazi Ivanishvili

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Radiation-induced various degrees of brain injury and cognitive impairment have been described after cranial radiotherapy of brain tumors. High doses of ionizing radiation have a severe impact on the central nervous system, resulting in morphological and behavioral impairments. Structures of the limbic system are especially sensitive to radiation exposure. Hence, compounds or drugs that can reduce radiation-induced impairments can be used as promising antioxidants or radioprotectors. In our study Mice whole-body irradiation with 137Cs was performed at a dose rate of 1,1 Gy/min for a total dose of 5 Gy with a “Gamma-capsule-2”. Irradiated mice were treated with Herniarin (20 mg/kg) for five days before irradiation and the same dose was administrated after one hour of irradiation. The immediate and delayed effects of ionizing radiation, as well as, protective effect of Herniarin was evaluated during early and late post-irradiation periods. The results reveal that ionizing radiation (5 Gy) alters the structure of the hippocampus in adult mice during the late post-irradiation period resulting in the decline of memory formation and learning process. Furthermore, Simple Coumarin-Herniarin reveals a radiosensitizing effect reducing morphological and behavioral alterations.

Keywords: ionizing radiation, cognitive impairments, hippocampus, limbic system, Herniarin

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Authors: Niousha Bagheri Khulenjani, Mohammad Saniee Abadeh

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Learning from very big datasets is a significant problem for most present data mining and machine learning algorithms. MicroRNA (miRNA) is one of the important big genomic and non-coding datasets presenting the genome sequences. In this paper, a hybrid method for the classification of the miRNA data is proposed. Due to the variety of cancers and high number of genes, analyzing the miRNA dataset has been a challenging problem for researchers. The number of features corresponding to the number of samples is high and the data suffer from being imbalanced. The feature selection method has been used to select features having more ability to distinguish classes and eliminating obscures features. Afterward, a Convolutional Neural Network (CNN) classifier for classification of cancer types is utilized, which employs a Genetic Algorithm to highlight optimized hyper-parameters of CNN. In order to make the process of classification by CNN faster, Graphics Processing Unit (GPU) is recommended for calculating the mathematic equation in a parallel way. The proposed method is tested on a real-world dataset with 8,129 patients, 29 different types of tumors, and 1,046 miRNA biomarkers, taken from The Cancer Genome Atlas (TCGA) database.

Keywords: cancer classification, feature selection, deep learning, genetic algorithm

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Authors: Ritesh Verma, Manisha Rathi, Chand Singh Dhull, Sumit Sachdeva, Jitender Phogat

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A Rathke's cleft cyst is a benign growth found on the pituitary gland in the brain, specifically a fluid-filled cyst in the posterior portion of the anterior pituitary gland. It occurs when the Rathke's pouch does not develop properly and ranges in size from 2 to 40mm in diameter. A 38-year-old male presented to the outpatient department with loss of vision in the inferior quadrant of the left eye since 15 days. Visual acuity was 6/6 in the right eye and 6/9 in the left eye. Visual field analysis by HFA-24-2 revealed an inferior field defect extending to the supero-temporal quadrant in the left eye. MRI brain and orbit was advised to the patient and it revealed a well defined cystic pituitary adenoma indenting left optic nerve near optic chiasm consistent with the diagnosis of Rathke’s cleft cyst (RCC). The patient was referred to neurosurgery department for further management. Symptoms vary greatly between individuals having RCCs. RCCs can be non-functioning, functioning, or both. Besides headaches, neurocognitive deficits are almost always present but have a high rate of immediate reversal if the cyst is properly treated or drained.

Keywords: pituitary tumors, rathke’s cleft cyst, visual field defects, vision loss

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Authors: A. Alao Olumuyiwa

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Health hazards reported to be associated with exposure to electromagnetic radiations which include brain tumors, genotoxic effects, neurological effects, immune system deregulation, allergic responses and some cardiovascular effects are discussed under a closed tabular model in this study. This review however showed that there is strong and robust evidence that chronic exposures to electromagnetic frequency across the spectrum, through strength, consistency, biological plausibility and many dose-response relationships, may result in brain cancer and other carcinogenic disease symptoms. There is therefore no safe threshold because of the genotoxic nature of the mechanism that may however be involved. The discussed study explains that the cell phone has induced effects upon the blood –brain barrier permeability and the cerebellum exposure to continuous long hours RF radiation may result in significant increase in albumin extravasations. A physical Biomodeling approach is however employed to review this health effects using Specific Absorption Rate (SAR) of different GSM machines to critically examine the symptoms such as a decreased loco motor activity, increased grooming and reduced memory functions in a variety of animal spices in classified grouped and sub grouped models.

Keywords: brain cancer, electromagnetic radiations, physical biomodeling, specific absorption rate (SAR)

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Authors: Huafeng Wei

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Dementia in Alzheimer’s Disease (AD) is the number one cause of dementia internationally, without effective treatments. Increasing evidence suggest that disruption of intracellular calcium homeostasis, primarily pathological elevation of cytosol and mitochondria but reduction of endoplasmic reticulum (ER) calcium concentrations, play critical upstream roles on multiple pathologies and associated neurodegeneration, impaired neurogenesis, synapse, and cognitive dysfunction in various AD preclinical studies. The last federal drug agency (FDA) approved drug for AD dementia treatment, memantine, exert its therapeutic effects by ameliorating N-methyl-D-aspartate (NMDA) glutamate receptor overactivation and subsequent calcium dysregulation. More research works are needed to develop other drugs targeting calcium dysregulation at multiple pharmacological acting sites for future effective AD dementia treatment. Particularly, calcium channel blockers for the treatment of hypertension and dantrolene for the treatment of muscle spasm and malignant hyperthermia can be repurposed for this purpose. In our own research work, intranasal administration of dantrolene significantly increased its brain concentrations and durations, rendering it a more effective therapeutic drug with less side effects for chronic AD dementia treatment. This review summarizesthe progress of various studies repurposing drugs targeting calcium dysregulation for future effective AD dementia treatment as potentially disease-modifying drugs.

Keywords: alzheimer, calcium, cognitive dysfunction, dementia, neurodegeneration, neurogenesis

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Authors: Ahmad Shanei, Mohammad Mahdi Shanei

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When a liquid is irradiated with high intensities (> 1 W) and low frequencies (≤ 1 MHz) ultrasound, acoustic cavitation occurs. Acoustic cavitation generates free radicals from the breakdown of water and other molecules. The existence of particles in liquid provide nucleation sites for cavitation bubbles and lead to decrease the ultrasonic intensity threshold needed for cavitation onset. The study was designed to measure hydroxyl radicals in terephthalic acid solutions containing 30 nm gold nanoparticles in a near field of a 1 MHz sonotherapy probe. The effect of ultrasound irradiation parameters containing mode of sonication and ultrasound intensity in hydroxyl radicals production have been investigated by the spectrofluorometry method. Recorded fluorescence signal in terephthalic acid solution containing gold nanoparticles was higher than the terephthalic acid solution without gold nanoparticles. Also, the results showed that any increase in intensity of the sonication would be associated with an increase in the fluorescence intensity. Acoustic cavitation in the presence of gold nanoparticles has been introduced as a way for improving therapeutic effects on the tumors. Also, the terephthalic acid dosimetry is suitable for detecting and quantifying free hydroxyl radicals as a criterion of cavitation production over a range of condition in medical ultrasound fields.

Keywords: acoustic cavitation, gold nanoparticle, chemical dosimetry, terephthalic acid

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Authors: Huafeng Wei

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Failures of developing new drugs primarily based on the amyloid pathology hypothesis after decades of efforts internationally lead to changes of focus targeting alternative pathways of pathology in Alzheimer’s disease (AD). Disruption of intracellular Ca2+ homeostasis, especially the pathological and excessive Ca2+ release from the endoplasmic reticulum (ER) via ryanodine receptor (RyRs) Ca2+ channels, has been considered an upstream pathology resulting in major AD pathologies, such as amyloid and Tau pathology, mitochondria damage and inflammation, etc. Therefore, dantrolene, an inhibitor of RyRs that reduces the pathological Ca2+ release from ER and a clinically available drug for the treatment of malignant hyperthermia and muscle spasm, is expected to ameliorate AD multiple pathologies synapse and cognitive dysfunction. Our own studies indicated that dantrolene ameliorated impairment of neurogenesis and synaptogenesis in neurons developed from induced pluripotent stem cells (iPSCs) originated from skin fibroblasts of either familiar (FAD) or sporadic (SAD) AD by restoring intracellular Ca2+ homeostasis. Intranasal administration of dantrolene significantly increased its passage across the blood-brain barrier (BBB) and, therefore its brain concentrations and durations. This can render dantrolene a more effective therapeutic drug with fewer side effects for chronic AD treatment. This review summarizes the potential therapeutic and side effects of dantrolene and repurposes intranasal dantrolene as a disease-modifying drug for future AD treatment.

Keywords: Alzheimer's disease, calcium, drug development, dementia, neurodegeneration, neurogenesis

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

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

Keywords: solid Tumor, docetaxel, targeting, NGR ligand

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Authors: Harukuni Tokuda, Xu FengHao, Nobutaka Suzuki

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As part of an ongoing our projects to investigate the anti-tumor promoring properties (chemopreventive potency) of Gromwell seed, dry powder materials and its active compounds were carried out through useful test systems. Gromwell seed (Coix lachryma-jobi seed) (GS) is a grass crop that has long been used and played a role in traditional medicine as a nourishing food, and for the treatment of various aliments, paticularly cancer. The application of a new screening procedure which utilizes the synergistic effect of short-chain fatty acids and phorbol esters in enable rapid and easy detection of naturally occurring substances(anti-tumor promoters chemo-preventive agents) with inhibition of Epstein-Barr virus(EBV) activation, using human lymphblastoid cells. In addition, we have now extended these investigations to a new tumorigenesis model in which we initiated the tumors with DMBA intiation and promoted with 1.7 nmol of TPA in two-stage mouse skin test and other models. these results provide a basis for further development of these botanical supplements for human cancer chemoprevention and observations seem that this materials more extensively as one of the trials for the purpose of complementary and alternative medicine.

Keywords: chemoprevention, medicinal plant, mouse, carcinogenesis systems

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Authors: Alireza Barari, Maryam Firozi-Niyaki, Maryam Kamarlouei

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Background: Herbs have a strong anti-cancer effect. Also, exercise is one of several lifestyle factors known to lower the risk of developing cancer. The aim of this study was to investigate the effect of endurance training and taxol on cyclooxygenase-2 and prostaglandin E2 in the liver tissue of mice with cervical cancer. Materials and Methods: In this experimental study, 35 female C57 mice were randomly divided into 5 groups (n=7 in each group): control (healthy), control (cancer), complement (cancer), training-supplementary (cancer) and training (cancer). The implantation of cancerous tumors was performed under the skin of the upper pelvis. The training group completed the endurance training protocol, which included 3 sessions per week, 50 minutes per session, at a speed of 14-18 m/s for six weeks. A dose of 60 mg/kg/day of pure taxol was injected intra peritoneally. The dependent variables of this study were measured 24 hours after the last training session by ELISA. Results: The results showed that the use of taxol and endurance training reduced the levels of cyclooxygenase-2 and prostaglandin E2 in the liver tissues of C57 mice with cervical cancer. Conclusion: Induction of the cancerous tissue in mice with cervical cancer increases the levels of cyclooxygenase-2 and prostaglandin E2 and endurance training along with taxol may reduce these levels.

Keywords: cervical cancer, taxol, endurance training, cyclooxygenase-2, prostaglandin E2

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Authors: Anupuma Raina, Ajay Parkash

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In forensic investigation, DNA analysis helps in the identification of a particular individual under investigation. A set of Short Tandem Repeats loci are widely used for individualization at a molecular level in forensic testing. STRs with tetrameric repeats of DNA are highly polymorphic and widely used for forensic DNA analysis. Identification of an individual became challenging for forensic examiners after Hematopoietic Stem Cell Transplantation. HSCT is a well-accepted and life-saving treatment to treat malignant and nonmalignant diseases. It involves the administration of healthy donor stem cells to replace the patient’s own unhealthy stem cells. A successful HSCT results in complete donor-derived cells in a patient’s hematopoiesis and hence have the capability to change the genetic makeup of the patient. Although an individual who has undergone HSCT and then committed a crime is a very rare situation, but not impossible. Keeping such a situation in mind, various biological samples like blood, buccal swab, and hair follicle were collected and studied after a certain interval of time after HSCT. Blood was collected from both the patient and the donor before the transplant. The DNA profile of both was analyzed using a short tandem repeat kit for autosomal chromosomes. Among all exhibits studied, only hair follicles were found to be the most suitable biological exhibit, as no donor DNA profile was observed for up to 90 days of study.

Keywords: chimerism, HSCT, STRs analysis, forensic identification

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Authors: Aditya Karade, Sharada Falane, Dhananjay Deshmukh, Vijaykumar Mantri

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Brain tumors pose a significant challenge in healthcare due to their complex nature and impact on patient outcomes. The application of deep learning (DL) algorithms in medical imaging have shown promise in accurate and efficient brain tumour detection. This paper explores the performance of various pre-trained DL models ResNet50, Xception, InceptionV3, EfficientNetB0, DenseNet121, NASNetMobile, VGG19, VGG16, and MobileNet on a brain tumour dataset sourced from Figshare. The dataset consists of MRI scans categorizing different types of brain tumours, including meningioma, pituitary, glioma, and no tumour. The study involves a comprehensive evaluation of these models’ accuracy and effectiveness in classifying brain tumour images. Data preprocessing, augmentation, and finetuning techniques are employed to optimize model performance. Among the evaluated deep learning models for brain tumour detection, ResNet50 emerges as the top performer with an accuracy of 98.86%. Following closely is Xception, exhibiting a strong accuracy of 97.33%. These models showcase robust capabilities in accurately classifying brain tumour images. On the other end of the spectrum, VGG16 trails with the lowest accuracy at 89.02%.

Keywords: brain tumour, MRI image, detecting and classifying tumour, pre-trained models, transfer learning, image segmentation, data augmentation

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Authors: Elham Ahmadi, Mehrdad Ravanshad, Joyce Fingeroth, Mazyar Ziyaeyan, Rajesh Panigrahi, Jun Xie, Gao Guangping

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B-cell proliferative disorders often occur among persons that are T-cell compromised. These disorders are primarily EBV+ and can first present with a focal lesion. Direct introduction of oncolytic viruses into localized tumors provides theoretical advantages over chemotherapy and immunotherapy by reducing systemic toxicity, to which the immunocompromised host is most vulnerable. Widely studied as a vehicle for gene therapy, AAV has only rarely been applied to treat cancer. As a prelude to development of a therapeutic vehicle, we assessed the ability of 15 distinct recombinant AAV serotypes (rAAV1, rAAV2, rAAV3b, rAAV4, rAAV5, rAAV6, rAAV6.2, rAAV6TM, rAAV7, rAAV8, rAAVrh8, rAAV9, rAAVrh10, rAAV39, rAAV43) bearing eGFP to infect human B-cell tumor lines compared with primary B-cells in vitro. Enhanced infection of tumor lines by AAV 6.2 was demonstrated by flow cytometry. EBV superinfection of EBV negative B-cell tumor lines increased susceptibility to AAV6.2 infection. As proof of concept, AAV6.2 bearing HSV-1 thymidine kinase in place of eGFP eliminated tumor cells upon exposure to ganciclovir.

Keywords: AAV, gene therapy, lymphoma, malignancy, tropism

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Authors: Tery Nehemia Nugraha Joseph, J. D. P. Wisnubroto

Abstract:

Thyroid cancer is a healthcare problem with high morbidity and mortality. Follicular adenoma and follicular carcinoma are thyroid tumors from the thyroid follicular cells differentiation with a microfollicular pattern that consists of follicular cuboidal cells. vascular endothelial growth factor (VEGF) is a potent and powerful mitogen for endothelial cells and increases vascular permeability. Therefore, due to an increase in thyroid-stimulating hormone (TSH), VEGF production is activated in the thyroid that leads to the end of mitogenic TSH stimulation and initiation of angiogenesis. The differences in VEGF levels in the follicular carcinoma of thyroid tissue with follicular adenoma thyroid can be used as a basis in differentiating the two types of neoplasms. This study aims to analyze VEGF in the serum so that it can be used to differentiate the types of thyroid carcinoma before surgery. This study uses a cross-sectional research design. Samples were carried out by taking serum samples, and the VEGF levels were calculated. Data were analyzed using the Mann-Whitney test. The results found a significant difference between VEGF levels in the follicular carcinoma thyroid group and VEGF levels in the follicular adenoma thyroid group with a value of p = 0.007 (p < 0.05). The results obtained are 560,427 ± 160,506 ng/mL in the type of follicular carcinoma thyroid and 320.943 ± 134.573 ng/mL in the type of follicular adenoma thyroid. VEGF levels between follicular adenoma and follicular carcinoma are different. VEGF levels are higher in follicular carcinoma thyroid than follicular adenoma thyroid.

Keywords: follicular adenoma thyroid, follicular carcinoma thyroid, thyroid, VEGF

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Authors: Pietro Mortini, Marco Losa

Abstract:

Objective: Resection of large lesions growing into the third ventricle remains a demanding surgery, sometimes at risk of severe post-operative complications. Transcallosal and transcortical routes were considered as approaches of choice to access the third ventricle, however neurological consequences like memory loss have been reported. We report clinical results of the previously described combined interhemispheric sub-commissural translaminaterminalis approach (CISTA) for the resection of large lesions located in the third ventricle. Methods: Authors conducted a retrospective analysis on 10 patients, who were operated through the CISTA, for the resection of lesions growing into the third ventricle. Results: Total resection was achieved in all cases. Cognitive worsening occurred only in one case. No perioperative deaths were recorded and, at last follow-up, all patients were alive. One year after surgery 80% of patients had an excellent outcome with a KPS 100 and Glasgow Outcome score (GOS) Conclusion: The CISTA represents a safe and effective alternative to transcallosal and transcortical routes to resect lesions growing into the third ventricle. It allows for a multiangle trajectory to access the third ventricle with a wide working area free from critical neurovascular structures, without any section of the corpus callosum, the anterior commissure and the fornix.

Keywords: craniopharingioma, surgery, sub-commissural translaminaterminalis approach (CISTA),

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Authors: Ya-Ching Wang, Yi-Maun Subeq

Abstract:

Background: There is a lack of evidence to understand differences in risk for developing breast cancer between sexual minority women and heterosexual women in Taiwan. The purpose of this study is to compare differences in risk for developing breast cancer between the two groups of Taiwanese women. Methods: An online cross-sectional survey was used to collect data. A total of 238 Taiwanese women (mean age 30.69 years old, SD=8.231, range 20-60) were recruited between December 2016 and February 2017, including 115 heterosexual women and 123 sexual minority women. Results: There were no significant differences between heterosexual women and sexual minority women in body mass index, history of non-malignant breast disease, age at menarche and menopause, use of hormone replacement therapy, use of hormone replacement therapy, nor the prevalence of breast cancer. The sexual minority women had higher rates of current drinking, smoking and using breast-bindings and also reported exercise more a week; the heterosexual women had higher rates of pregnancy, children, breastfeed, miscarriages, abortion and use of birth control pills. Discussion/Conclusion: There were significant differences between heterosexual women and sexual minority women in reproductive factors and behavioral risk factors for the development of breast cancer. In particular, the finding that the sexual minority women had higher rate of using breast-bindings (56.6%) than the heterosexual women (4.7%) should be further explore, in order to understand whether long-term breast compression is associated with the development of breast cancer.

Keywords: breast cancer, risk, sexual orientation, Taiwan

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Authors: Alireza Javed, Keivan Jamshidi

Abstract:

Reactive amyloidosis is a condition that complicates a long list of chronic inflammation, chronic infectious, malignant, and hereditary disorders. In the present study the potential effects of two amyloidogenic substances: ie. AgNO3 and Freund's Adjuvant (AF) with that of vitamin free casein, on spatio-temporal pattern of experimental amyloidosis in mice, were compared. For this purpose, a total of 40 male Swees mice, obtained from Pasteur Institute Tehran, after being weighted were randomly divided into 4 groups including 2 treatments, 1 control (vitamin free casein) and 1 positive control (normal saline). At the end of 3rd, 5th and 7th weeks of experiment 3 mice were randomly selected and euthnised. Spleen sample of each animal obtained and preserved in 10% neutral buffer formalin. Sample were then processed through different stages of dehydration, clearing and impregnation and finally embedded in paraffin blocks. Sections of 5µm thickness then cut and stained by alkaline Congo red techniques. Spleen weights and the data obtained from the microscopic quantitative analysis did show no significant differences between groups A and B, A and C, and B and C. However, significant differences were observed between groups A and D, B and D, and C and D respectively. It is concluded that two compounds ie; AgNO3 and Freund's Adjuvant have the same potential, as does vitamin free casein have, in spatio – temporal pattern of experimental amyloidosis in mice.

Keywords: amyloidosis, mice, AgNO3, Freund's Adjuvant

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Authors: Simeon Mayala, Ida Herdlevær, Jonas Bull Haugsøen, Shamundeeswari Anandan, Sonia Gavasso, Morten Brun

Abstract:

In this paper, we propose a minimum spanning tree-based method for segmenting brain tumors. The proposed method performs interactive segmentation based on the minimum spanning tree without tuning parameters. The steps involve preprocessing, making a graph, constructing a minimum spanning tree, and a newly implemented way of interactively segmenting the region of interest. In the preprocessing step, a Gaussian filter is applied to 2D images to remove the noise. Then, the pixel neighbor graph is weighted by intensity differences and the corresponding minimum spanning tree is constructed. The image is loaded in an interactive window for segmenting the tumor. The region of interest and the background are selected by clicking to split the minimum spanning tree into two trees. One of these trees represents the region of interest and the other represents the background. Finally, the segmentation given by the two trees is visualized. The proposed method was tested by segmenting two different 2D brain T1-weighted magnetic resonance image data sets. The comparison between our results and the standard gold segmentation confirmed the validity of the minimum spanning tree approach. The proposed method is simple to implement and the results indicate that it is accurate and efficient.

Keywords: brain tumor, brain tumor segmentation, minimum spanning tree, segmentation, image processing

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Authors: Naif Al-Jomah, Falah H Al-Mohanna, Abdelilah Aboussekhra

Abstract:

Active breast cancer-associated fibroblasts (CAFs), the most influential cells in breast tumor microenvironment, express/secrete high levels of the proinvasive/metastatic interleukin-6 (IL-6). Therefore, we have tested here the effect of the IL-6 receptor (IL-6R) inhibitor tocilizumab (TCZ; Actemra) on different active breast CAFs. We have shown that TCZ potently and persistently suppresses the expression of various CAF biomarkers, namely α-SMA, SDF-1 as well as the STAT3 pathway and its downstream target AUF1. TCZ also inhibited the proliferation, migration and invasion abilities of active breast CAF cells. Additionally, TCZ repressed the ability of CAF cells in promoting epithelial-to-mesenchymal transition, and enhancing the migratory/invasive and proliferative capacities of breast cancer cells in vitro. Importantly, these findings were confirmed in orthotopic humanized breast tumors in mice. Furthermore, TCZ suppressed the expression of the pro-angiogenic factor VEGF-A and its transactivator HIF-1α in CAF cells, and consequently inhibited the angiogenic-promoting effect of active CAFs both in vitro and in orthotopic tumor xenografts. These results indicate that inhibition of the IL-6/STAT3/AUF1 pathway by TCZ can normalize active breast CAFs and suppress their paracrine pro-carcinogenic effects, which paves the way toward development of specific CAF-targeting therapy, badly needed for more efficient breast cancer treatments.

Keywords: angiogenesis, interleukin-6, paracrine, cancer-associated fibroblasts

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