Search results for: inhibition of cancer cells

Authors: Doaa Hashad, Amany Elbanna, Abeer Ibrahim, Gihan Khedr

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Background: H19 is one of the long non coding RNAs (LncRNA) that is related to the progression of many diseases including cancers. This work was carried out to study the level of the long non-coding RNA; H119, in plasma of patients with gastric cancer (GC) and to assess its significance in their clinical management. Methods: A total of sixty-two participants were enrolled in the present study. The first group included thirty-two GC patients, while the second group was formed of thirty age and sex matched healthy volunteers serving as a control group. Plasma samples were used to assess H19 gene expression using real time quantitative PCR technique. Results: H19 expression was up-regulated in GC patients with positive correlation to TNM cancer stages. Conclusions: Up-regulation of H19 is closely associated with gastric cancer and correlates well with tumor staging. Convenient, efficient quantification of H19 in plasma using real time PCR technique implements its role as a potential noninvasive prognostic biomarker in gastric cancer, that predicts patient’s outcome and most importantly as a novel target in gastric cancer treatment with better performance achieved on using both CEA and H19 simultaneously.

Keywords: biomarker, gastric, cancer, LncRNA

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Authors: Sara Pereira-Nogueira, Tim Worbs, Marc Permanyer-Bosser, Reinhold Förster

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While the entry mechanism of lymphocytes into the lymph node via the blood are well described, it is still largely unknown how cells enter lymph nodes that arrive via afferent lymphatics. In order to address this, our group has established a micro-injection technique in mice through which cells are delivered directly into the lymphatic vessel immediately afferent to the popliteal lymph node. Injected cells can then be tracked via multi-colour fluorescence or 2-photon microscopy, and their localization can be analysed within the popliteal or downstream lymph nodes by immunohistology. Since naïve B cells express the chemokine receptor CXCR5 we intra-lymphatically co-injected B cells derived from wildtype and Cxcr5-deficient mice. While CXCR5 does not play a role in guiding B cells out of the subcapsular sinus, it affects their positioning within the lymph node parenchyma, since CXCR5-deficient B cells are impaired in migrating into the B cell follicle. The knowledge obtained by studying B-cell migration may prove beneficial in clinical settings regarding tumor metastasis or autoimmune diseases.

Keywords: afferent lymphatics, B cell migration, chemokine, intra-lymphatic injection

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Authors: L. Szymanski, Z. Kolacinski, Z. Kamiński, G. Raniszewski, J. Fraczyk, L. Pietrzak

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In the article the development and demonstration of method and the model device for hyperthermic selective destruction of cancer cells are presented. This method was based on the synthesis and functionalization of carbon nanotubes serving as ferromagnetic material nano containers. Methodology of the production carbon - ferromagnetic nanocontainers includes: the synthesis of carbon nanotubes, chemical and physical characterization, increasing the content of ferromagnetic material and biochemical functionalization involving the attachment of the key addresses. Biochemical functionalization of ferromagnetic nanocontainers is necessary in order to increase the binding selectively with receptors presented on the surface of tumour cells. Multi-step modification procedure was finally used to attach folic acid on the surface of ferromagnetic nanocontainers. Folic acid is ligand of folate receptors which is overexpresion in tumor cells. The presence of ligand should ensure the specificity of the interaction between ferromagnetic nanocontainers and tumor cells. The chemical functionalization contains several step: oxidation reaction, transformation of carboxyl groups into more reactive ester or amide groups, incorporation of spacer molecule (linker), attaching folic acid. Activation of carboxylic groups was prepared with triazine coupling reagent (preparation of superactive ester attached on the nanocontainers). The spacer molecules were designed and synthesized. In order to ensure biocompatibillity of linkers they were built from amino acids or peptides. Spacer molecules were synthesized using the SPPS method. Synthesis was performed on 2-Chlorotrityl resin. The linker important feature is its length. Due to that fact synthesis of peptide linkers containing from 2 to 4 -Ala- residues was carried out. Independent synthesis of the conjugate of foilic acid with 6-aminocaproic acid was made. Final step of synthesis was connecting conjugat with spacer molecules and attaching it on the ferromagnetic nanocontainer surface. This article contains also information about special CVD and microvave plasma system to produce nanotubes and ferromagnetic nanocontainers. The first tests in the device for hyperthermal RF generator will be presented. The frequency of RF generator was in the ranges from 10 to 14Mhz and from 265 to 621kHz.

Keywords: synthesis of carbon nanotubes, hyperthermia, ligands, carbon nanotubes

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Authors: Jacek Kabzinski, Karolina Przybylowska, Lukasz Dziki, Adam Dziki, Ireneusz Majsterek

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The incidence of colorectal cancer (CRC) is increasing from year to year. Despite intensive research CRC etiology remains unknown. Studies suggest that at the basis of the process of carcinogenesis can lie reduced efficiency of DNA repair mechanisms, often caused by polymorphisms in DNA repair genes. The aim of the study was to determine the relationship between gene polymorphisms Pro242Arg of PolB gene and Arg780His of Lig3 gene and modulation of the risk of colorectal cancer in the Polish population. Determination of the molecular basis of carcinogenesis process and predicting increased risk will allow qualifying patients to increased risk group and including them in preventive program. We used blood collected from 110 patients diagnosed with colorectal cancer. The control group consisted of equal number of healthy people. Genotyping was performed by TaqMan method. The obtained results indicate that the genotype 780Arg/His of Lig3 gene is associated with an increased risk of colorectal cancer. On the basis of these results, we conclude that Lig3 gene polymorphism Arg780His may be associated with an increased risk of colorectal cancer.

Keywords: BER, colorectal cancer, PolB, Lig3, polymorphisms

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Authors: Geeta Sharma, Suma Chandra

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Sugarcane is one of the major commercial crop playing roles in agriculture and industrial economy of India. Globally sugarcane is affected by approximately 240 diseases caused by various plant pathogenic organisms. Among them, red rot disease caused by the fungus Colletotrichum falcatum, is one of the most important diseases. In the present investigation, one fungal bioagent of Trichoderma harzianum, Pant Bioagent 1 and one bacterial bioagent Pseudomonas fluorescence, Pant Bioagent 2 (PBAT 1 and PBAT 2, respectively) were tested by dual culture method against the pathogen under laboratory conditions. The effectiveness of biocontrol agents was observed against four isolates of C. falcatum. In the case of PBAT1 maximum percent inhibition of pathogen was recorded in isolated Cf 0238 (61.05%), followed by Cf 09 (60.62%) whereas, minimum percent inhibition was recorded in Cf 3220 (48.55%) and in case of PBAT2 maximum mycelial growth inhibition percent was recorded in Cf 767 (50.50%) followed by Cf 088230(48.83%), whereas minimum percent inhibition was recorded in Cf 08 (40.16%) followed by Cf 0238 (41.83%). The present study showed that these biocontrol agents have the potential of controlling the pathogen and can further be used for the management of red rot disease in field.

Keywords: biocontrol agents, Colletotrichum falcatum, isolates, sugarcane

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Authors: Oseyemi O. Olubomehin, Edith O. Ajaiyeoba, Kio A. Abo, Eleonora D. Goosen

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Diabetes is a major degenerative disease of global concern and it is the third most lethal disease of mankind, accounting for about 3.2 million deaths annually. Lowering postprandial hyperglycemia by inhibition of carbohydrate hydrolyzing enzyme such as alpha-amylase is one of the therapeutic approaches to treat Type 2 Diabetes. Alpha-amylase inhibitors from plants have been found to be effective in managing postprandial hyperglycemia. In continuation of our anti-diabetic activities of this plant, bioassay-guided fractionation and isolation using 0.1-1.0 mg/mL furnished djalonenol, a monoterpene diol with a significant 53.7% α-amylase inhibition (p<0.001) from the stem bark which was comparable to acarbose which gave a 54.9% inhibition. Spectral characterization using Infra-red, Gas Chromatogrphy-Mass spectrometry, 1D and 2D NMR of the isolated compound was done to elucidate the structure of the compound.

Keywords: alpha-amylase inhibitor, hyperglycemia, postprandial, diabetes

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Authors: Sajjad Seifi Mofarah, S. K. Sadrnezhaad, Shokooh Moghadam, Javad Tavakoli

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In recent years a new method of combination treatment for cancer has been developed and studied that has led to significant advancements in the field of cancer therapy. Hyperthermia is a traditional therapy that, along with a creation of a medically approved level of heat with the help of an alternating magnetic AC current, results in the destruction of cancer cells by heat. This paper gives details regarding the production of the spherical nanocomposite PVA/γ-Fe2O3 in order to be used for medical purposes such as tumor treatment by hyperthermia. To reach a suitable and evenly distributed temperature, the nanocomposite with core-shell morphology and spherical form within a 100 to 200 nanometer size was created using phase separation emulsion, in which the magnetic nano-particles γ-Fe2O3 with an average particle size of 20 nano-meters and with different percentages of 0.2, 0.4, 0.5, and 0.6 were covered by polyvinyl alcohol. The main concern in hyperthermia and heat treatment is achieving desirable specific absorption rate (SAR) and one of the most critical factors in SAR is particle size. In this project all attempts has been done to reach minimal size and consequently maximum SAR. The morphological analysis of the spherical structure of the nanocomposite PVA/γ-Fe2O3 was achieved by SEM analyses and the study of the chemical bonds created was made possible by FTIR analysis. To investigate the manner of magnetic nanocomposite particle size distribution a DLS experiment was conducted. Moreover, to determine the magnetic behavior of the γ-Fe2O3 particle and the nanocomposite PVA/γ-Fe2O3 in different concentrations a VSM test was conducted. To sum up, creating magnetic nanocomposites with a spherical morphology that would be employed for drug loading opens doors to new approaches in developing nanocomposites that provide efficient heat and a controlled release of drug simultaneously inside the magnetic field, which are among their positive characteristics that could significantly improve the recovery process in patients.

Keywords: nanocomposite, hyperthermia, cancer therapy, drug releasing

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Authors: Mehrnaz Mostafavi, Mahtab Shabani, Alireza Azani, Fatemeh Ghafari

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Artificial intelligence (AI) can transform breast cancer diagnosis and therapy by providing sophisticated solutions for screening, imaging interpretation, histopathological analysis, and treatment planning. This literature review digs into the many uses of AI in breast cancer treatment, highlighting the need for collaboration between AI scientists and healthcare practitioners. It emphasizes advances in AI-driven breast imaging interpretation, such as computer-aided detection and diagnosis (CADe/CADx) systems and deep learning algorithms. These have shown significant potential for improving diagnostic accuracy and lowering radiologists' workloads. Furthermore, AI approaches such as deep learning have been used in histopathological research to accurately predict hormone receptor status and categorize tumor-associated stroma from regular H&E stains. These AI-powered approaches simplify diagnostic procedures while providing insights into tumor biology and prognosis. As AI becomes more embedded in breast cancer care, it is crucial to ensure its ethical, efficient, and patient-focused implementation to improve outcomes for breast cancer patients ultimately.

Keywords: breast cancer, artificial intelligence, cancer diagnosis, clinical practice

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Authors: Shiva Rezaei, Seyed Jalal Hosseinimehr, Abbasali Karimpour Malekshah, Mansooreh Mirzaei, Fereshteh Talebpour Amiri, Mehryar Zargari

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Objective(s): Cyclophosphamide (CP), as an antineoplastic drug, is widely used in cancer patients, and liver toxicity is one of its complications. Sinapic acid (SA), as a natural phenylpropanoid, has antioxidant, anti-inflammatory, and anti-cancer properties. Materials and Methods: The purpose of the current study was to determine the protective effect of SA versus CP-induced liver toxicity. In this research, BALB/c mice were treated with SA (5 and 10 mg/kg) orally for one week, and CP (200 mg/kg) was injected on day 3 of the study. Oxidative stress markers, serum liver-specific enzymes, histopathological features, caspase-3, and nuclear factor kappa-B cells were then checked. Results: CP induced hepatotoxicity in mice and showed structural changes in liver tissue. CP significantly increased liver enzymes and lipid peroxidation and decreased glutathione. The immunoreactivity of caspase-3 and nuclear factor kappa-B cells was significantly increased. Administration of SA significantly maintained histochemical parameters and liver function enzymes in mice treated with CP. Immunohistochemical examination showed SA reduced apoptosis and inflammation. Conclusion: The data confirmed that SA with anti-apoptotic, anti-oxidative, and anti-inflammatory activities was able to preserve CP-induced liver injury in mice.

Keywords: apoptosis, cyclophosphamide, liver injury, inflammation, oxidative stress, sinapic acid

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Authors: Emmanuel Jaluchimike Iloputaife, Kelechi Nkechinyere Mbah-Omeje

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This study was designed to determine the antimicrobial activities and minimum inhibitory concentration of three different batches (Fresh, Oven dried and Sundried) of Ass Hay extracted with water, ethanol and methanolagainst selected human pathogenic microorganisms (Escherichia coli, Klebsiella Pneumonia, Staphylococcus aureus, Aspergillus niger and Candidaalbicans). All extracts were reconstituted with peptone water and tested for antimicrobial activity. The antimicrobial activity, the Minimum Inhibitory Concentration and Minimum Bactericidal/Fungicidal concentrations were determined by agar well diffusion methodagainst test organismsin which aseptic conditions were observed. The antimicrobial activities of the different batches of Ass Hay on the test organisms varied considerably. The highest inhibition zone diameter at 200 mg/ml for the different batches of Ass Hay was recorded by sundried methanol extract against Escherichia coli at 36.4 ± 0.2 mm while fresh methanol extract inhibited Klebsiela pneumonia with the least inhibition zone diameter at 20.1 ± 0.1mm. At 100 mg/ml the highest inhibition zone diameter was recorded by oven dried water extract against Escherichia coli at 30.3 ± 0.3 mm while sun dried water extract inhibited Staphylococcus aureus with the least inhibition zone diameter at 15.1 ± 0.1 mm. At 50mg/ml, the highest inhibition zone diameter was recorded by fresh water extract against Escherichia coli at 25.9 ± 0.1 mm while oven dried water extract inhibited Klebsiela pneumonia with least inhibition zone diameter at 12.1 ± 0.2 mm. At 25mg/ml, the highest inhibition zone diameter was recorded by fresh water extract against Escherichia coli at 18.3 ± 0.2 mm while sun dried ethanol extract inhibited Escherichia coli with least inhibition zone diameter at 10.1 ± 0.1 mm. The MIC and MBC result of ethanol extract of fresh Ass Hay showed a uniform value of 6.25 mg/ml and 12.5 mg/ml respectively for all test bacterial isolates. The Minimum Inhibitory concentration and Minimum bactericidal concentration results of Oven dried ethanol Ass Hay extract showed a uniform value of 3.125 mg/ml and 6.25 mg/ml respectively for all test bacterial isolates and Minimum fungicidal concentration value of 12.5 mg/ml for Aspergillus niger. Statistical analysis showed there is significant difference in mean zone inhibition diameter of the products at p < 0.05, p = 0.019. This study has shown there is antimicrobial potential in Ass Hay and at such there is need to further exploit Donkey Ass Hay in order to maximize the potential.

Keywords: microorganisms, Ass Hay, antimicrobial activity, extracts

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Authors: Pei-Yu Lee

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This study investigates the life experience and self-interpretation of female cervical cancer patients under Taiwanese cultural context. Through a Narrative Analysis Research approach, the study took six cervical cancer female patients with an average age of 58 years (ranging from 55-66 years) for an average of twice, 60 minutes each time, in-depth recorded interviews under their consent. After converting the interview recordings into transcripts, the study applied the Riessman approach to analyze the contents. The results revealed two major theme, including 1. The symbolic meaning of the cervix, and 2. Women's perseverance and compliance. Because of the illness metaphor of cervical cancer and the designation of women being family caregivers under the Chinese patriarchal culture, females with cervical cancer are not only patients but also responsible for being family and partner roles, in which contradictions of intimate relationships exist. Show the strength of perseverance and compliance in the course of life. On the other hand, they have to identify and recognize their roles in life and strive to determine the situation of coexisting with the disease to picture their life. The results showed that female cervical cancer patients not only need to combat the disease but also stand against the stigma and the traditional responsibility given to women. The researchers recommend that nurses should include cultural implications in their care of female cervical cancer patients.

Keywords: female, cervical cancer, narrative analysis research, taiwan

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Authors: Nidal H. Abu-Zahra, Aruna P. Wanninayake

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Copper Oxide (CuO) is a p-type semiconductor with a band gap energy of 1.5 eV, this is close to the ideal energy gap of 1.4 eV required for solar cells to allow good solar spectral absorption. The inherent electrical characteristics of CuO nano particles make them attractive candidates for improving the performance of polymer solar cells when incorporated into the active polymer layer. The UV-visible absorption spectra and external quantum efficiency of P3HT/PC70BM solar cells containing different weight percentages of CuO nano particles showed a clear enhancement in the photo absorption of the active layer, this increased the power conversion efficiency of the solar cells by 24% in comparison to the reference cell. The short circuit current of the reference cell was found to be 5.234 mA/cm2 and it seemed to increase to 6.484 mA/cm2 in cells containing 0.6 mg of CuO NPs; in addition the fill factor increased from 61.15% to 68.0%, showing an enhancement of 11.2%. These observations suggest that the optimum concentration of CuO nano particles was 0.6 mg in the active layer. These significant findings can be applied to design high-efficiency polymer solar cells containing inorganic nano particles.

Keywords: copper oxide nanoparticle, UV-visible spectroscopy, polymer solar cells, P3HT/PCBM

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Authors: Kakali Bhadra

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Harmalol administration caused remarkable reduction in proliferation of HepG₂ cells with GI₅₀ of 14.2 mM, without showing much cytotoxicity in embryonic liver cell line, WRL-68. Data from circular dichroism and differential scanning calorimetric analysis of harmalol-CT DNA complex shows conformational changes with prominent CD perturbation and stabilization of CT DNA by 8 ^oC. Binding constant and stoichiometry was also calculated using the above biophysical techniques. Further, dose dependent apoptotic induction ability of harmalol was studied in HepG₂ cells using different biochemical assays. Generation of ROS, DNA damage, changes in cellular external and ultramorphology, alteration of membrane, formation of comet tail, decreased mitochondrial membrane potential and a significant increase in Sub G_o/G₁ population made the cancer cell, HepG₂, prone to apoptosis. Up regulation of p53 and caspase 3 further indicated the apoptotic role of harmalol.

Keywords: apoptosis, beta carboline alkaloid, comet assay, cytotoxicity, ROS

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Authors: Karthik Mittal

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This study performs an unsupervised machine learning analysis to find clusters of related SNPs which highlight biological pathways that are important for the biological mechanisms of breast cancer. Studying genetic variations in isolation is illogical because these genetic variations are known to modulate protein production and function; the downstream effects of these modifications on biological outcomes are highly interconnected. After extracting the SNPs and their effect on different types of breast cancer using the MRBase library, two unsupervised machine learning clustering algorithms were implemented on the genetic variants: a k-means clustering algorithm and a hierarchical clustering algorithm; furthermore, principal component analysis was executed to visually represent the data. These algorithms specifically used the SNP’s beta value on the three different types of breast cancer tested in this project (estrogen-receptor positive breast cancer, estrogen-receptor negative breast cancer, and breast cancer in general) to perform this clustering. Two significant genetic pathways validated the clustering produced by this project: the MAPK signaling pathway and the connection between the BRCA2 gene and the ESR1 gene. This study provides the first proof of concept showing the importance of unsupervised machine learning in interpreting GWAS summary statistics.

Keywords: breast cancer, computational biology, unsupervised machine learning, k-means, PCA

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Authors: Jae-Hyeon Kim, Michael Lee

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Intrinsic and acquired resistance limits the therapeutic benefits of oncogenic BRAF inhibitors in melanoma. MicroRNAs (miRNA) regulate the expression of target mRNAs by repressing their translation. Thus, we investigated miRNA expression patterns in melanoma cell lines to identify candidate biomarkers for acquired resistance to BRAF inhibitor. Here, we used Affymetrix miRNA V3.0 microarray profiling platform to compare miRNA expression levels in three cell lines containing BRAF inhibitor-sensitive A375P BRAF V600E cells, their BRAF inhibitor-resistant counterparts (A375P/Mdr), and SK-MEL-2 BRAF-WT cells with intrinsic resistance to BRAF inhibitor. The miRNAs with at least a two-fold change in expression between BRAF inhibitor-sensitive and –resistant cell lines, were identified as differentially expressed. Averaged intensity measurements identified 138 and 217 miRNAs that were differentially expressed by 2 fold or more between: 1) A375P and A375P/Mdr; 2) A375P and SK-MEL-2, respectively. The hierarchical clustering revealed differences in miRNA expression profiles between BRAF inhibitor-sensitive and –resistant cell lines for miRNAs involved in intrinsic and acquired resistance to BRAF inhibitor. In particular, 43 miRNAs were identified whose expression was consistently altered in two BRAF inhibitor-resistant cell lines, regardless of intrinsic and acquired resistance. Twenty five miRNAs were consistently upregulated and 18 downregulated more than 2-fold. Although some discrepancies were detected when miRNA microarray data were compared with qPCR-measured expression levels, qRT-PCR for five miRNAs (miR-3617, miR-92a1, miR-1246, miR-1936-3p, and miR-17-3p) results showed excellent agreement with microarray experiments. To further investigate cellular functions of miRNAs, we examined effects on cell proliferation. Synthetic oligonucleotide miRNA mimics were transfected into three cell lines, and proliferation was quantified using a colorimetric assay. Of the 5 miRNAs tested, only miR-1246 altered cell proliferation of A375P/Mdr cells. The transfection of miR-1246 mimic strongly conferred PLX-4720 resistance to A375P/Mdr cells, implying that miR-1246 upregulation confers acquired resistance to BRAF inhibition. We also found that PLX-4720 caused much greater G2/M arrest in A375P/Mdr cells transfected with miR-1246mimic than that seen in scrambled RNA-transfected cells. Additionally, miR-1246 mimic partially caused a resistance to autophagy induction by PLX-4720. These results indicate that autophagy does play an essential death-promoting role inPLX-4720-induced cell death. Taken together, these results suggest that miRNA expression profiling in melanoma cells can provide valuable information for a network of BRAF inhibitor resistance-associated miRNAs.

Keywords: microRNA, BRAF inhibitor, drug resistance, autophagy

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Authors: Hyunjung Lim, Jeonghun Nam, Hyuk Choi

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High-throughput separation is an essential technique for cancer research and diagnosis. Here, we propose a viscoelastic microfluidic device for sheathless, high-throughput isolation of circulating tumor cells (CTCs) from white blood cells. Here, we demonstrate a viscoelastic method for separation and concentration of CTCs using closed-loop microfluidics. Our device is a rectangular straight channel with a low aspect ratio. Also, to achieve high-efficiency, high-throughput processing, we used a polymer solution with low viscosity. At the inlet, CTCs and white blood cells (WBCs) were randomly injected into the microchannel. Due to the viscoelasticity-induced lateral migration to the equilibrium positions, large CTCs could be collected from the side outlet while small WBCs were removed at the center outlet. By recirculating the collected CTCs from the side outlet back to the sample reservoir, continuous separation and concentration of CTCs could be achieved with high separation efficiency (~ 99%). We believe that our device has the potential to be applied in resource-limited clinical settings.

Keywords: circulating tumor cell, closed-loop microfluidics, concentration, separation, viscoelastic fluid

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Authors: Diwei Lin, Amanda Jia Hui Tan

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In 2012, testicular cancer was estimated to account for 940 disability adjusted life years in Australia; of these, 450 were years lost due to premature death and 500 were years of healthy life lost due to disease, disability or injury. Testicular choriocarcinoma is one of the rarest variants of testicular germ cell tumours, accounting for less than 1% of testicular germ cell tumours and only about 0.19% of all testicular tumours. Management involves radical orchiectomy followed by chemotherapy. Even then, the prognosis is extremely poor. This case report describes a 20-year-old male with pure testicular choriocarcinoma with pulmonary metastases.

Keywords: testicular cancer, choriocarcinoma, cryptorchidism, chemotherapy, metastatic testicular cancer

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Authors: Lamis Naddaf, Yuval Tabach

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In this research, we identified the missense genetic variants that have the potential to enhance resistance against cancer. Such field has not been widely explored, as researchers tend to investigate mutations that cause diseases, in response to the suffering of patients, rather than those mutations that protect from them. In conjunction with the genomic revolution, and the advances in genetic engineering and synthetic biology, identifying the protective variants will increase the power of genotype-phenotype predictions and can have significant implications on improved risk estimation, diagnostics, prognosis and even for personalized therapy and drug discovery. To approach our goal, we systematically investigated the sites of the coding genomes and picked up the alleles that showed a correlation with the species’ cancer resistance. We predicted 250 protecting variants (PVs) with a 0.01 false discovery rate and more than 20 thousand PVs with a 0.25 false discovery rate. Cancer resistance in Mammals and reptiles was significantly predicted by the number of PVs a species has. Moreover, Genes enriched with the protecting variants are enriched in pathways relevant to tumor suppression like pathways of Hedgehog signaling and silencing, which its improper activation is associated with the most common form of cancer malignancy. We also showed that the PVs are more abundant in healthy people compared to cancer patients within different human races.

Keywords: comparative genomics, machine learning, cancer resistance, cancer-protecting alleles

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Authors: Rajapaksha Gedara Prasad Tharanga Jayasooriya, Matharage Gayani Dilshara, Yung Hyun Choi, Gi-Young Kim

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Camptothecin (CPT) is a quinolone alkaloid which inhibits DNA topoisomerase I that induces cytotoxicity in a variety of cancer cell lines. We previously showed that CPT effectively inhibited invasion of prostate cancer cells and also combined treatment with subtoxic doses of CPT and TNF-related apoptosis-inducing ligand (TRAIL) potentially enhanced apoptosis in a caspase-dependent manner in hepatoma cancer cells. Here, we found that treatment with CPT caused an irreversible cell cycle arrest in the G2/M phase. CPT-induced cell cycle arrest was associated with a decrease in protein levels of cell division cycle 25C (Cdc25C) and increased the level of cyclin B and p21. The CPT-induced decrease in Cdc25C was blocked in the presence of proteasome inhibitor MG132, thus reversed the cell cycle arrest. In addition to that treatment of CPT-increased phosphorylation of Cdc25C was the resulted of activation of checkpoint kinase 2 (Chk2), which was associated with phosphorylation of ataxia telangiectasia-mutated. Interestingly CPT induced G2/M phase of the cell cycle arrest is reactive oxygen species (ROS) dependent where ROS inhibitors NAC and GSH reversed the CPT-induced cell cycle arrest. These results further confirm by using transient knockdown of nuclear factor-erythroid 2-related factor 2 (Nrf2) since it regulates the production of ROS. Our data reveal that treatment of siNrf2 increased the ROS level as well as further increased the CPT induce G2/M phase cell cycle arrest. Our data also indicate CPT-enhanced cell cycle arrest through the extracellular signal-regulated kinase (ERK) and the c-Jun N-terminal kinase (JNK) pathway. Inhibitors of ERK and JNK more decreased the Cdc25C expression and protein expression of p21 and cyclin B. These findings indicate that Chk2-mediated phosphorylation of Cdc25C plays a major role in G2/M arrest by CPT.

Keywords: camptothecin, cell cycle, checkpoint kinase 2, nuclear factor-erythroid 2-related factor 2, reactive oxygen species

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Authors: Bliss Singhal

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Machine learning (ML) is a branch of Artificial Intelligence (AI) where computers analyze data and find patterns in the data. The study focuses on the detection of metastatic cancer using ML. Metastatic cancer is the stage where cancer has spread to other parts of the body and is the cause of approximately 90% of cancer-related deaths. Normally, pathologists spend hours each day to manually classifying whether tumors are benign or malignant. This tedious task contributes to mislabeling metastasis being over 60% of the time and emphasizes the importance of being aware of human error and other inefficiencies. ML is a good candidate to improve the correct identification of metastatic cancer, saving thousands of lives and can also improve the speed and efficiency of the process, thereby taking fewer resources and time. So far, the deep learning methodology of AI has been used in research to detect cancer. This study is a novel approach to determining the potential of using preprocessing algorithms combined with classification algorithms in detecting metastatic cancer. The study used two preprocessing algorithms: principal component analysis (PCA) and the genetic algorithm, to reduce the dimensionality of the dataset and then used three classification algorithms: logistic regression, decision tree classifier, and k-nearest neighbors to detect metastatic cancer in the pathology scans. The highest accuracy of 71.14% was produced by the ML pipeline comprising of PCA, the genetic algorithm, and the k-nearest neighbor algorithm, suggesting that preprocessing and classification algorithms have great potential for detecting metastatic cancer.

Keywords: breast cancer, principal component analysis, genetic algorithm, k-nearest neighbors, decision tree classifier, logistic regression

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Authors: Soultana Konstantinidou, Tiziana Schmidt, Elena Landi, Alessandro De Carli, Giovanni Maltinti, Darius Witt, Alicja Dziadosz, Agnieszka Lindstaedt, Michele Lai, Mauro Pistello, Valentina Cappello, Luciana Dente, Chiara Gabellini, Piotr Barski, Vittoria Raffa

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CRISPR/Cas9 technology has gained the interest of researchers in the field of biotechnology for genome editing. Since its discovery as a microbial adaptive immune defense, this system has been widely adopted and is acknowledged for having a variety of applications. However, critical barriers related to safety and delivery are persisting. Here, we propose a new concept of genome engineering, which is based on a nano-formulation of Cas9. The Cas9 enzyme was conjugated to a gold nanoparticle (AuNP-Cas9). The AuNP-Cas9 maintained its cleavage efficiency in vitro, to the same extent as the ribonucleoprotein, including non-conjugated Cas9 enzyme, and showed high gene editing efficiency in vivo in zebrafish embryos. Since CRISPR/Cas9 technology is extensively used in cancer research, melanoma was selected as a validation target. Cell studies were performed in A375 human melanoma cells. Particles per se had no impact on cell metabolism and proliferation. Intriguingly, the AuNP-Cas9 internalized spontaneously in cells and localized as a single particle in the cytoplasm and organelles. More importantly, the AuNP-Cas9 showed a high nuclear localization signal. The AuNP-Cas9, overcoming the delivery difficulties of Cas9, could be used in cellular biology and localization studies. Taking advantage of the plasmonic properties of gold nanoparticles, this technology could potentially be a bio-tool for combining gene editing and photothermal therapy in cancer cells. Further work will be focused on intracellular interactions of the nano-formulation and characterization of the optical properties.

Keywords: CRISPR/Cas9, gene editing, gold nanoparticles, nanotechnology

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Authors: K. Barbaro, F. Di Egidio, A. Amaddeo, G. Lupoli, S. Eramo, G. Barraco, D. Amaddeo, C. Gallottini

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In this study, we wanted to evaluate the effects of nano-hydroxy apatite (NHA) on mesenchymal stem cells extracted from subcutaneous adipose tissue of the dog. The stem cells were divided into 6 experimental groups at different concentrations of NHA. The comparison was made with a control group of stem cell grown in standard conditions without NHA. After 1 week, the cells were fixed with 10% buffered formalin for 1 hour at room temperature and stained with Giemsa, measured at the inverted optical microscope. The morphological evaluation of the control samples and those treated showed that stem cells adhere to the substrate and proliferate in the presence of nanohydroxy apatite at different concentrations showing no detectable toxic effects.

Keywords: nano-hydroxy apatite, adipose mesenchymal stem cells, dog, morphological evaluation

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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

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Authors: A. Asselah, A. Khalfi, M. A.Toumi, A.Tazerouti

Abstract:

The study of the corrosion inhibition of a standard carbon steel "API 5L grade X70" by two biodegradable anionic surfactants derived from fatty acids by photo sulfochlorination, called sodium lauryl methyl ester sulfonates and sodium palmityl methyl ester sulfonates was carried. A solution at 2.5 g/l NaCl saturated with carbon dioxide is used as a corrosive medium. The gravimetric and electrochemical technics (stationary and transient) were used in order to quantify the rate of corrosion and to evaluate the electrochemical inhibition efficiency, thus the nature of the mode of action of the inhibitor, in addition to a surface characterization by scanning electron microscopy (MEB) coupled to energy dispersive X-ray spectroscopy (EDX). The variation of the concentration and the temperature were examined, and the mode of adsorption of these inhibitors on the surface of the metal was established by assigning it the appropriate isotherm and determining the corresponding thermodynamic parameters. The MEB-EDX allowed the visualization of good adhesion of the protective film formed by the surfactants to the surface of the steel. The corrosion inhibition was evaluated at around 93% for sodium lauryl methyl ester sulfonate surfactant at 20 ppm and 87.2% at 50 ppm for sodium palmityl methyl ester sulfonate surfactant.

Keywords: carbon steel, oilfield, corrosion, anionic surfactants

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Authors: Ferreira RC, Simons HZ, Thompson WS, Cutler AJ, Dopico XC, Smyth DJ, Mashar M, Schuilenburg H, Walker NM, Dunger DB, Wallace C, Todd JA, Wicker LS, Pekalski ML

Abstract:

Type 1 diabetes is caused by autoimmune destruction of insulin-secreting beta cells in the pancreas. T cells are known to play an important role in this immune-mediated destruction; however, there is no general consensus regarding alterations in cytokine production or T cell subsets in peripheral blood of patients with type 1 diabetes. Using polychromatic flow cytometry of peripheral blood mononuclear cells (PBMCs), we assessed production of the proinflammatory cytokines IL-21, IFN-γ and IL-17 by memory CD4 T effector (Teff) cells in 69 patients with type 1 diabetes and 61 healthy donors. We found a 21.9% (95% CI 5.8, 40.2; p = 3.9 × 10(-3)) higher frequency of IL-21(+) CD45RA(-) memory CD4(+) Teffs in patients with type 1 diabetes (geometric mean 5.92% [95% CI 5.44, 6.44]) compared with healthy donors (geometric mean 4.88% [95% CI 4.33, 5.50]). In a separate cohort of 30 patients with type 1 diabetes and 32 healthy donors, we assessed the frequency of circulating T follicular helper (Tfh) cells in whole blood. Consistent with the increased production of IL-21, we also found a 14.9% increase in circulating Tfh cells in the patients with type 1 diabetes (95% CI 2.9, 26.9; p = 0.016). Analysis of IL-21 production by PBMCs from a subset of 46 of the 62 donors immunophenotyped for Tfh showed that frequency of Tfh cells was associated with the frequency of IL-21+ cells (r2 = 0.174, p = 0.004). These results indicate that increased IL-21 production is likely to be an aetiological factor in the pathogenesis of type 1 diabetes that could be considered as a potential therapeutic target.

Keywords: T follicular helper cell, IL-21, IL-17, type 1 diabetes

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Authors: Alka Yadav, Mayank Jain, Rajan Saxena, Niraj Kumari, Narendra Krishnani, Ashok Kumar

Abstract:

Purpose: To study the mismatch repair (MMR) protein expression and its clinicopathological correlation in colorectal cancer patients in North India. Methods: A prospective study was conducted on histologically proven 52 (38 males and 14 females) patients with adenocarcinoma of colorectum. MMR protein loss was determined by using immunohistochemistry for MLH1, MSH2, PMS2 and MSH6. Results: 52 patients (38 males and 14 females) underwent resection for colorectal cancer with the median age of 52 years (16-81 years). 35% of the patients (n=18) were younger than 50 years of the age. 3 patients had associated history of malignancy in the family. 29 (56%) patients had right colon cancer, 9 (17%) left colon cancer and 14 (27%) rectal cancer. 2 patients each had synchronous and metachronous cancer. Histology revealed well-differentiated tumour in 16, moderately differentiated in 10 and poorly differentiated tumour in 26 patients. MMR protein loss was seen in 15 (29%) patients. Seven (46%) of these patients were less than 50 years of age. Combined loss of MSH2 and MSH6 was seen most commonly and it was found in 6 patients. 12 (80%) patients with MMR protein loss had tumour located proximal to the splenic flexure compared to 3 (20%) located distal to the splenic flexure. There was no difference in MMR protein loss based on patients' age, gender, degree of tumour differentiation, stage of the disease and tumour histological characteristics. Conclusions: This study revealed that there was less than 30% MMR protein loss in colorectal cancer patients. The loss was most commonly seen in right sided colon cancer than left. A larger study is further required to validate these findings.

Keywords: colorectal cancer, mismatch repair protein, immunohitochemistry, clinicopathological correlation

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Authors: Rana F. Obeidat, Suzanne S. Dickerson, Gregory G. Homish, Nesreen M. Alqaissi, Robin M. Lally

Abstract:

Background: Despite the fact that breast cancer is the most prevalent cancer among Jordanian women, practically nothing is known about their perceptions of early stage breast cancer and surgical treatment. Objective: To gain understanding of the diagnosis and surgical treatment experience of Jordanian women diagnosed with early stage breast cancer. Methods: An interpretive phenomenological approach was used for this study. A purposive sample of 28 Jordanian women who were surgically treated for early stage breast cancer within 6 months of the interview was recruited. Data were collected using individual interviews and analyzed using Heideggerian hermeneutical methodology. Results: Fear had a profound effect on Jordanian women’s stories of diagnosis and surgical treatment of early stage breast cancer. Women’s experience with breast cancer and its treatment was shaped by their pre-existing fear of breast cancer, the disparity in the quality of care at various health care institutions, and sociodemographic factors (e.g., education, age). Conclusions: Early after the diagnosis, fear was very strong and women lost perspective of the fact that this disease was treatable and potentially curable. To control their fears, women unconditionally trusted God, the health care system, surgeons, family, friends, and/or neighbors, and often accepted treatment offered by their surgeons without questioning. Implications for practice: Jordanian healthcare providers have a responsibility to listen to their patients, explore meanings they ascribe to their illness, and provide women with proper education and support necessary to help them cope with their illness.

Keywords: breast cancer, early stage, Jordanian, experience, phenomenology

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Authors: Kefaya Qaddoum

Abstract:

The aim of this study is to predict breast cancer and to construct a supportive model that will stimulate a more reliable prediction as a factor that is fundamental for public health. In this study, we utilize general regression neural networks (GRNN) to replace the normal predictions with prediction periods to achieve a reasonable percentage of confidence. The mechanism employed here utilises a machine learning system called conformal prediction (CP), in order to assign consistent confidence measures to predictions, which are combined with GRNN. We apply the resulting algorithm to the problem of breast cancer diagnosis. The results show that the prediction constructed by this method is reasonable and could be useful in practice.

Keywords: neural network, conformal prediction, cancer classification, regression

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Authors: Gabriel Hunduma

Abstract:

Asymptomatic intra-thoracic neurogenic tumours are rare. Tumours arising from the intercostal nerves of the chest wall are exceedingly rare. This paper reports an incidental discovery of a neurogenic intercostal tumour while being investigated for Coronavirus Disease 2019 (COVID-19). A 54-year-old female underwent a thoracotomy and resection for an intercostal tumour. Pre-operative images showed an intrathoracic mass, and the biopsy revealed a schwannoma. The most common presenting symptom recorded in literature is chest pain; however, our case remained asymptomatic despite the size of the mass and thoracic area it occupied. After an extensive search of the literature, COVID-19 was found to have an influence on the development of certain cells in breast cancer. Hence there is a possibility that COVID-19 played a role in progressing the development of the schwannoma cells.

Keywords: thoracic surgery, intercostal schwannoma, chest wall oncology, COVID-19

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Authors: Natasha Petrovska, Mirjana Pavlovic, Maria M. Larrondo-Petrie

Abstract:

Neural stem cells (NSCs) are multi-potent, self-renewing cells that generate new neurons. Three subtypes of NSCs can be separated regarding the stages of NSC lineage: quiescent neural stem cells (qNSCs), activated neural stem cells (aNSCs) and neural progenitor cells (NPCs), but their gene expression signatures are not utterly understood yet. Single-cell examinations have started to elucidate the complex structure of NSC populations. Nevertheless, there is a lack of thorough molecular interpretation of the NSC lineage heterogeneity and an increasing need for tools to analyze and improve the efficiency and correctness of single-cell sequencing data. Feature selection and ordering can identify and classify the gene expression signatures of these subtypes and can discover novel subpopulations during the NSCs activation and differentiation processes. The aim here is to review the implementation of the feature selection technique on NSC subtypes and the classification techniques that have been used for the identification of gene expression signatures.

Keywords: feature selection, feature similarity, neural stem cells, genes, feature selection methods

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