Search results for: nonsmall cell lung cancer

Authors: Philippa Saunders, Claire Fletcher

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INTRODUCTION: Prostate cancer is the most prevalent malignancy affecting Western males. It is initially an androgen-dependent disease: androgens bind to the androgen receptor and drive the expression of genes that promote proliferation and evasion of apoptosis. Despite reduced androgen dependence in advanced prostate cancer, androgen receptor signaling remains a key driver of growth. Androgen deprivation therapy (ADT) is, therefore, a first-line treatment approach and works well initially, but resistance inevitably develops. Abiraterone and Enzalutamide are drugs widely used in ADT and are androgen synthesis and androgen receptor signaling inhibitors, respectively. The shortage of other treatment options means acquired resistance to these drugs is a major clinical problem. MicroRNAs (miRs) are important mediators of post-transcriptional gene regulation and show altered expression in cancer. Several have been linked to the development of resistance to ADT. Manipulation of such miRs may be a pathway to breakthrough treatments for advanced prostate cancer. This study aimed to validate ADT resistance-implicated miRs and their clinically relevant targets. MATERIAL AND METHOD: Small RNA-sequencing of Abiraterone- and Enzalutamide-resistant C42 prostate cancer cells identified subsets of miRs dysregulated as compared to parental cells. Real-Time Quantitative Reverse Transcription PCR (qRT-PCR) was used to validate altered expression of candidate ADT resistance-implicated miRs 195-5p, 497-5p and 29a-5p in ADT-resistant and -responsive prostate cancer cell lines, patient-derived xenografts (PDXs) and primary prostate cancer explants. RESULTS AND DISCUSSION: This study suggests a possible role for miR-497-5p in the development of ADT resistance in prostate cancer. MiR-497-5p expression was increased in ADT-resistant versus ADT-responsive prostate cancer cells. Importantly, miR-497-5p expression was also increased in Enzalutamide-treated, castrated (ADT-mimicking) PDXs versus intact PDXs. MiR-195-5p was also elevated in ADT-resistant versus -responsive prostate cancer cells, while there was a drop in miR-29a-5p expression. Candidate clinically relevant targets of miR-497-5p in prostate cancer were identified by mining AGO-PAR-CLIP-seq data sets and may include AVL9 and FZD6. CONCLUSION: In summary, this study identified microRNAs that are implicated in prostate cancer resistance to androgen deprivation therapy and could represent novel therapeutic targets for advanced disease.

Keywords: microRNA, androgen deprivation therapy, Enzalutamide, abiraterone, patient-derived xenograft

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Authors: Alaa M. Badr Eldin, Mayar M. Shahen, Mohammed S. Sedeek, Marwa I. Ezzat, Sawsan M. ElSonbaty, Muhammed A. Saad, Manal S. Afifi, Omar M. Sabry

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Using HPLC-MS/MS technique, 133 polyphenolic compounds were identified in the methanol extract of pomegranate rind (Punica granatum L.). In-vitro cytotoxic activity against breast cancer cell line MCF-7 was investigated, with an IC50 of 54 ug/ml. In-silico molecular docking using ellagic acid, gallagic acid, and Punicalagin as model compounds identified in pomegranate rind extract confirmed the intriguing anti-estrogenic action of the key polyphenolic components in pomegranate rind extract. Surprisingly, taxol showed low activity compared to pomegranate compounds as ERα antagonist and ERβ agonist. Pomegranate rind extract enhanced apoptosis of breast cancer cells through upregulation of the caspase-3 expression and downregulation of NF-κB transcription factor.

Keywords: HPLC-MS/MS, pomegranate rind, cytotoxicity, MCF-7, ER, caspase-3, NF-kB

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Authors: Po-Jung Huang, Chi-Ching Lee, Bertrand Chin-Ming Tan, Yuan-Ming Yeh, Julie Lichieh Chu, Tin-Wen Chen, Cheng-Yang Lee, Ruei-Chi Gan, Hsuan Liu, Petrus Tang

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Whole-exome sequencing focuses on the protein coding regions of disease/cancer associated genes based on a priori knowledge is the most cost-effective method to study the association between genetic alterations and disease. Recent advances in high throughput sequencing technologies and proteomic techniques has provided an opportunity to integrate genomics and proteomics, allowing readily detectable mutated peptides corresponding to mutated genes. Since sequence database search is the most widely used method for protein identification using Mass spectrometry (MS)-based proteomics technology, a mutant proteome database is required to better approximate the real protein pool to improve disease-associated mutated protein identification. Large-scale whole exome/genome sequencing studies were launched by National Cancer Institute (NCI), Broad Institute, and The Cancer Genome Atlas (TCGA), which provide not only a comprehensive report on the analysis of coding variants in diverse samples cell lines but a invaluable resource for extensive research community. No existing database is available for the collection of mutant protein sequences related to the identified variants in these studies. CMPD is designed to address this issue, serving as a bridge between genomic data and proteomic studies and focusing on protein sequence-altering variations originated from both germline and cancer-associated somatic variations.

Keywords: TCGA, cancer, mutant, proteome

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Authors: Samaneh Farokhirad, Fatemeh Ahmadpoor

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Biological membranes are constantly in contact with various filamentous soft nanostructures that either reside on their surface or are being transported between the cell and its environment. In particular, viral infections are determined by the interaction of viruses (such as filovirus) with cell membranes, membrane protein organization (such as cytoskeletal proteins and actin filament bundles) has been proposed to influence the mechanical properties of lipid membranes, and the adhesion of filamentous nanoparticles influence their delivery yield into target cells or tissues. The goal of this research is to integrate the rapidly increasing but still fragmented experimental observations on the adhesion and self-assembly of nanofilaments (including filoviruses, actin filaments, as well as natural and synthetic nanofilaments) on cell membranes into a general, rigorous, and unified knowledge framework. The global outbreak of the coronavirus disease in 2020, which has persisted for over three years, highlights the crucial role that nanofilamentbased delivery systems play in human health. This work will unravel the role of a unique property of all cell membranes, namely flexoelectricity, and the significance of nanofilaments’ flexibility in the adhesion and self-assembly of nanofilaments on cell membranes. This will be achieved utilizing a set of continuum mechanics, statistical mechanics, and molecular dynamics and Monte Carlo simulations. The findings will help address the societal needs to understand biophysical principles that govern the attachment of filoviruses and flexible nanofilaments onto the living cells and provide guidance on the development of nanofilament-based vaccines for a range of diseases, including infectious diseases and cancer.

Keywords: virus nanofilaments, cell mechanics, computational biophysics, statistical mechanics

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Authors: Fatma Zuhrotun Nisa, Aprilina Ratriany, Agus Wijanarka

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Background: Cassava leaves are widely used by the people of Indonesia as a vegetable and treat various diseases, including anticancer believed as food. However, not much research on the anticancer activity of cassava leaves, especially in colon cancer. Objectives: the aim of this study is to investigate anti-cancer activity of cassava leaves (Manihot esculanta C.) against colon cancer (WiDr) cells in vitro. Methods: effect of crude aqueous extract of leaves of cassava and cassava leaves boiled tested in colon cancer cells widr. Determination of Anticancer uses the MTT method with parameters such as the percentage of deaths. Results: raw cassava leaf water extract gave IC50 of 63.1 mg / ml. While the water extract of boiled cassava leaves gave IC50 of 79.4 mg/ml. However, there is no difference anticancer activity of raw cassava leaves or cancer (p> 0.05). Conclusion: Cassava leaves contain a variety of compounds that have previously been reported to have anticancer activity. Linamarin, β-carotene, vitamin C, and fiber were thought to affect the IC50 cassava leaf extract against colon cancer cells WiDr.

Keywords: boiled cassava leaves, cassava leaves raw, anticancer activity, colon cancer, IC50

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Authors: Mary Kiviiri Nakawuka, Mary Namugalu, Andrew Otiti

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BACKGROUND Cervical cancer is the fourth most common cancer in women and seventh overall among all cancers worldwide. It accounts for about 7.5% of all female-cancer deaths with 85% occurring in low and middle-income countries and the first most common female cancer in women aged 15 to 44 years in Uganda with an annual number of new cases at 3,915 and 2,275 annual number of cervical cancer deaths in 2012 (ICO INFORMATION CENTRE ON HPV AND CANCER, 2017).Despite the available free cervical cancer screening services whose uptake has been documented to improve the chances of successful treatment of pre-cancers and cancers among women of reproductive age, there is a low uptake of these services thus we sought to examine the uptake of cervical cancer services and associated factors among women of reproductive age (25-49) attending the ART clinic of KISWA HCII in Kampala, Uganda METHODS The research was carried out in the ART clinic of KISWA HCII among 385 participants. An analytical, cross-sectional study with quantitative methods of data collection was used. The study adopted a non-probability convenience sampling method to select participants. Quantitative data was collected through structured questionnaires. RESULTS 72.2% of the participants were found to have been screened for cervical cancer. 36 % of the screened women had a positive HPV or VIA result ,59.2% of the screened women had a negative HPV or VIA result and 4.8% had an invalid HPV test result. Only 39.5% of the participants had adequate overall knowledge about cervical cancer, more than a third of the participants (50%) had moderate or low knowledge and minority of them (10.5%) had no knowledge. There was no significant association between the uptake of cervical cancer screening services among participants and their socio-demographic characteristics. CONCLUSIONS Although majority of the women surveyed had been screened for cervical cancer, a comparatively large number of participants had inadequate knowledge about cervical cancer and therefore there is still need to continue teaching about cervical cancer and this may include education campaigns, improvements to the accessibility and convenience of the screening services.

Keywords: cervical cancer uptake, cervical cancer screening, women of reproductive age., cervical cancer knowledge

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Authors: S. Tebibel, C. Mechati, S. Messaoudi

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Algeria is currently experiencing the same rate of cancer progression as that registered these last years in the western countries. Colorectal cancer, constituting increasingly a major public health problem, is the most common form of cancer after breast and Neck-womb cancer at the woman and prostate cancer at the man. Our work is based on a retrospective study to determine the cases of colorectal cancer through eastern Algeria. Our goal is to carry out an epidemiological, histological and immune- histochemical study to investigate different techniques for the diagnosis of colorectal cancer and their interests and specific in detecting the disease. The study includes 110 patients (aged between 20 to 87 years) with colorectal cancer where the inclusions and exclusions criteria were established. In our study, colorectal cancer, expresses a male predominance, with a sex ratio of 1, 99 and the most affected age group is between 50 and 59 years. We noted that the colon cancer rate is higher than rectal cancer rate, whose frequencies are respectively 60,91 % and 39,09 %. In the series of colon cancer, the ADK lieberkunien is histological the most represented type, or 85,07 % of all cases. In contrast, the proportion of ADK mucinous (colloid mucous) is only 1,49% only. Well-differentiated ADKS, are very significant in our series, they represent 83,58 % of cases. Adenocarcinoma moderately and poorly differentiated, whose proportions are respectively 2,99 % and 0.05 %. For histological varieties of rectal ADK, we see in our workforce that ADK lieberkunien represent the most common histological form, or 76,74%, while the mucosal colloid is 13,95 %. Research of the mutation on the gene encoding K-ras, a major step in the targeted therapy of colorectal cancers, is underway in our study. Colorectal cancer is the subject of much promising research concern: the evaluation of new therapies (antiangiogenic monoclonal antibodies), the search for predictors of sensitivity to chemotherapy and new prognostic markers using techniques of molecular biology and proteomics.

Keywords: adenocarcinoma, age, colorectal cancer, epidemiology, histological section, sex

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Authors: Efendi Zaenudin, Chien-Hung Huang, Ka-Lok Ng

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Essential genes play an important role in the survival of an organism. It has been shown that cancer-associated essential genes are genes necessary for cancer cell proliferation, where these genes are potential therapeutic targets. Also, it was demonstrated that mutations of the cancer-associated essential genes give rise to the resistance of immunotherapy for patients with tumors. In the present study, we focus on studying the biological effects of the essential genes from a network perspective. We hypothesize that one can analyze a biological molecular network by decomposing it into both three-node and four-node digraphs (subgraphs). These network subgraphs encode the regulatory interaction information among the network’s genetic elements. In this study, the frequency of occurrence of the subgraph-associated essential genes in a molecular network was quantified by using the statistical parameter, odds ratio. Biological effects of subgraph-associated essential genes are discussed. In summary, the subgraph approach provides a systematic method for analyzing molecular networks and it can capture useful biological information for biomedical research.

Keywords: biological molecular networks, essential genes, graph theory, network subgraphs

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Authors: Dipranjan Laha, Parimal Karmakar

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Metal oxide nanoparticles are well known to generate oxidative stress and deregulate normal cellular activities. Among these, transition metals copper oxide nanoparticles (CuO NPs) are more compelling than others and able to modulate different cellular responses. In this work, we have synthesized and characterized CuO NPs by various biophysical methods. These CuO NPs (~30 nm) induce autophagy in human breast cancer cell line, MCF7 in a time and dose-dependent manner. Cellular autophagy was tested by MDC staining, induction of green fluorescent protein light chain 3 (GFP-LC3B) foci by confocal microscopy, transfection of pBABE-puro mCherry-EGFP-LC3B plasmid and western blotting of autophagy marker proteins LC3B, beclin1, and ATG5. Further, inhibition of autophagy by 3-Methyladenine (3-MA) decreased LD50 doses of CuO NPs. Such cell death was associated with the induction of apoptosis as revealed by FACS analysis, cleavage of PARP, dephosphorylation of Bad and increased cleavage product of caspase3. siRNA-mediated inhibition of autophagy-related gene beclin1 also demonstrated similar results. Finally, induction of apoptosis by 3-MA in CuO NPs treated cells were observed by TEM. This study indicates that CuO NPs are a potent inducer of autophagy which may be a cellular defense against the CuO NPs mediated toxicity and inhibition of autophagy switches the cellular response into apoptosis. A combination of CuO NPs with the autophagy inhibitor is essential to induce apoptosis in breast cancer cells. Acknowledgments: The authors would like to acknowledge for financial support for this research work to the Department of Biotechnology (No. BT/PR14661/NNT/28/494/2010), Government of India.

Keywords: nanoparticle, autophagy, apoptosis, siRNA-mediated inhibition

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Authors: Niall Fennessy, Charlotte Yin, Vineet Gorolay, Michael Chan, Ilias Drivas

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Background: The aim of this study was to evaluate the effect of manual aspiration of air from the pleural cavity in mitigating the need for chest drain placement after a CT-guided lung biopsy. Method: This is a single institution retrospective review of CT-guided lung biopsies performed on 799 patients between September 2013 and May 2021 in a major tertiary hospital. Percutaneous manual aspiration of air was performed in 104/306 patients (34%) with pneumothoraxes as a preventative measure. Simple and multivariate analysis was performed to identify independent risk factors (modifiable and nonmodifiable) for the success of manual aspiration in mitigating the need for chest drain insertion. Results: The overall incidence of pneumothorax was 37% (295/799). Chest drains were inserted for 81/295 (27%) of the pneumothoraxes, representing 81/799 (10%) of all CT-guided lung biopsies. Of patients with pneumothoraces, 104 (36%) underwent percutaneous aspiration via either the coaxial guide needle or an 18 or 20G intravenous catheter attached to a three-way stopcock and syringe. Amongst this group, 13 patients (13%) subsequently required chest drain insertion. The success of percutaneous aspiration in avoiding subsequent pleural drain insertion decreased with aspiration volume >500mL, radial pneumothorax depth >3cm, increased subpleural depth of the lesion, and the presence of background emphysema.

Keywords: computed tomography, lung biopsy, pneumothorax, manual aspiration, chest drainage

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Authors: Aiza G. Clanor, Lotlot B. Hernandez, Jonna Marie T. Ibuna

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This study aimed to know the coping mechanisms of Batangueño families facing cancer, specifically, those from Cancer Warriors Foundation, Inc. Batangas chapter. The researchers used purposive sampling. This study was limited to the responses provided by the Batangueño families of the cancer patients. A family member of the immediate family with a child facing cancer represents the family as a whole. A total number of forty six (46) respondents were given the questionnaires. Upon analysis, most of the respondents came from rural areas and nuclear family and have Php 5000 and below family monthly income. Most of them have their own houses, and 3 to 5 members, one of whom is a cancer patient diagnosed for more than 2 years. The two most frequently utilized coping strategies were mobilizing the family to acquire and accept help, and reframing. Passive appraisal is the least utilized one. There was a significant difference on the coping mechanisms of the family relative to passive appraisal based on the length of time since the illness was first diagnosed. Based from the study, the researchers developed modules with discussions and activities on cancer awareness, ideas on coping and how to deal with the cancer patients that may help the respondents and other Batangueño families overcome the difficulties in facing cancer. The researchers recommend the modules for they are found to be effective ways to help the families relieve stress, reduce anxiety and improve quality of life.

Keywords: coping with chronic illness, family, psychology, cancer

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Authors: S. P. Chintan, A. M. Khoja, M. Modi, R. K. Chopra, S. Garde, D. Jain, O. Kajale

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Pulmonary Hypertension is a rare but debilitating disease that affects individuals of all ages and walks of life. As recent as 15 years ago, a patient diagnosed with PH was given an average survival rate of 2.8 years. Recent advances in treatment options have allowed patients to improve quality o and quantity of life. Initial screening for PH is through echocardiography with final diagnosis confirmed through right heart catheterization. PH is now considered to have five major classifications with subgroups among each. The mild to moderate PH is common in chronic lung diseases like Chronic obstructive pulmonary diseases and Interstitial lung disease. But very severe PH is noted in few cases. In COPD patients, PH is associated with an increased risk of severe exacerbations and a reduced life expectancy. Similarly, in patients with ILD, the presence of PH correlates with a poor prognosis. Early diagnosis is essential to slow disease progression. We report here five cases of severe PH (Out of Proportion) of which four cases were of COPD and another one of IPF (UIP pattern). There echocardiography showed gross RA/RV dilatation, interventricular septum bulging to the left and mPAP of more than 100 mmHg in all the five cases. These patients were put on LTOT, pulmonary rehabilitation, combination pharmacotherapy of vasodilators and diuretics in continuation to the treatment of underlying disease. As these patients have grave prognosis close monitoring and follow up is required. Physicians associated with respiratory care and treating chronic lung disease should have knowledge in the diagnosis and management of patients with PH.

Keywords: COPD, pulmonary hypertension, chronic lung disease, India

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Authors: Devasis Ghosh

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The main hindrance to total cure of cancer is a) the failure to control continued production of cancer cells, b) its sustenance and c) its metastasis. This review study has tried to address this issue of total cancer cure in a more innovative way. A 10-pronged “CRAB METHOD”, a novel holistic scientific approach of Cancer treatment has been hypothesized in this paper. Apart from available Chemotherapy, Radiotherapy and Oncosurgery, (which shall not be discussed here), seven other points of interference and treatment has been suggested, i.e. 1. Efficient stress management. 2. Dampening of ATF3 expression. 3. Selective inhibition of Platelet Activity. 4. Modulation of serotonin production, metabolism and 5HT receptor antagonism. 5. Auxin, its anti-proliferative potential and its modulation. 6. Melatonin supplementation because of its oncostatic properties. 7. HDAC Inhibitors especially valproic acid use due to its apoptotic role in many cancers. If all the above stated seven steps are thoroughly taken care of at the time of initial diagnosis of cancer along with the available treatment modalities of Chemotherapy, Radiotherapy and Oncosurgery, then perhaps, the morbidity and mortality rate of cancer may be greatly reduced.

Keywords: ATF3 dampening, auxin modulation, cancer, platelet activation, serotonin, stress, valproic acid

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Authors: Muslim Idan Mohsin, Mohammed Jasim Al-Shamarti, Rusul Idan Mohsin, Ali A. Majeed

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One of the causative agents of the lower respiratory tract (LRT) is Pseudomonas aeruginosa, which can lead to severe infection associated with a lung infection. There are many cytokines that are secreted in response to bacterial infection, in particular interleukin IL-36 cytokine in response to P. aeruginosa infection. The involvement of IL-36 in the P. aeruginosa infection could be a clue to find a specific way for treatments of different inflammatory and degenerative lung diseases. IL36 promotes primary immune response via binding to the IL-36 receptor (IL-36R). Indeed, an overactivity of IL-36 might be an initiating factor for many immunopathologic sceneries in pneumonia. Here we demonstrate if the IL-36 cytokine increases in response P. aeruginosa infection that is isolated from lower respiratory tract infection (LRT). We demonstrated that IL-36 expression significantly unregulated in human lung epithelial (A549) cells after infected by P. aeruginosa at mRNA level.

Keywords: IL36, Pseudomonas aeruginosa, LRT infection, A549 cells

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Authors: Somit Dutta, Pallab Kar, Arnab Kumar Chakraborty, Arnab Sen, Tapas Kumar Chaudhuri

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In the present study three species of Clerodendrum; Clerodendrum indicum, Volkameria inermis and Clerodendrum colebrookianum were used to investigate the possible activity against oxidative stress. A detailed in-vivo and in-vitro antioxidant profiling, directly associated with inflammation-related carcinogenesis, has been executed with a motive to evaluate the free radical scavenging activity of Clerodendrum extract. Measurement of cell viability and ROS generation in HEK-293 (Human Embryonic Kidney Cell Line) cells was also estimated. The immune cell proliferative properties (MTT) and in-vitro assay for evaluation of their antioxidant activities including hydroxyl radical, nitric oxide, singlet oxygen, peroxinitrate and hydrogen peroxide, etc. were investigated. GC-MS and FTIR analyses have been performed to identify the active biological compounds. These active biological compounds were further studied to assess their potential medicinal properties, aided by molecular docking and interaction analysis between the active compounds and different proteins related to oxidative stress leading to progression of carcinogenesis. The research article clearly demonstrates the role of ROS in various phases of carcinogenesis. Therefore, the antioxidant and free radical scavenging capacity of all the Clerodendrum species might prove beneficial for the immune system. It might be concluded that this plant species offers great promise for cancer prevention and therapy due to the presence of several bioactive compounds and potent antioxidant capacity of C. colebrookianum.

Keywords: antioxidant, cancer, oxidative stress, reactive oxygen species (ROS)

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Authors: Jer-Yuh Liu, Je-Chiuan Ye, Jin-Ming Hwang

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Protein kinase C alpha (PKCα) is a key signaling molecule in human cancer development. As a therapeutic strategy, targeting PKCα is difficult because the molecule is ubiquitously expressed in non-malignant cells. PKCα is regulated by the cooperative interaction of the transcription factors myeloid zinc finger 1 (MZF-1) and Ets-like protein-1 (Elk-1) in human cancer cells. By conducting tissue array analysis, herein, we determined the protein expression of MZF-1/Elk-1/PKCα in various cancers. The data show that the expression of MZF-1/Elk-1 is correlated with that of PKCα in hepatocellular carcinoma (HCC), but not in bladder and lung cancers. In addition, the PKCα down-regulation by shRNA Elk-1 was only observed in the HCC SK-Hep-1 cells. Blocking the interaction between MZF-1 and Elk-1 through the transfection of their binding domain MZF-160–72 decreased PKCα expression. This step ultimately depressed the epithelial-mesenchymal transition potential of the HCC cells. These findings could be used to develop an alternative therapeutic strategy for patients with the PKCα-derived HCC.

Keywords: protein kinase C alpha, myeloid zinc finger 1, ets-like protein-1, hepatocellular carcinoma

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Authors: Reynaldo Esquivel, Pedro Hernandez, Aaron Martinez-Higareda, Sergio Tena-Cano, Enrique Alvarez-Ramos, Armando Lucero-Acuna

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Stimuli-responsive nanomaterials play an essential role in loading, transporting and well-distribution of anti-cancer compounds in the cellular surroundings. The outstanding properties as the Lower Critical Solution Temperature (LCST), hydrolytic cleavage and protonation/deprotonation cycle, govern the release and delivery mechanisms of payloads. In this contribution, we experimentally determine the load efficiency and release of antineoplastic Vincristine Sulfate into PNIPAM-Interpenetrated-Chitosan (PIntC) nanoparticles. Structural analysis was performed by Fourier Transform Infrared Spectroscopy (FT-IR) and Proton Nuclear Magnetic Resonance (1HNMR). ζ-Potential (ζ) and Hydrodynamic diameter (DH) measurements were monitored by Electrophoretic Mobility (EM) and Dynamic Light scattering (DLS) respectively. Mathematical analysis of the release pharmacokinetics reveals a three-phase model above LCST, while a monophasic of Vincristine release model was observed at 32 °C. Cytotoxic essays reveal a noticeable enhancement of Vincristine effectiveness at low drug concentration on HeLa cervix cancer and MDA-MB-231 breast cancer.

Keywords: nanoparticles, vincristine, drug delivery, PNIPAM

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Authors: Sehreen Moorat, Mussarat Lakho

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A method of artificial intelligence using digital mammograms data has been proposed in this paper for detection of breast cancer. Many researchers have developed techniques for the early detection of breast cancer; the early diagnosis helps to save many lives. The detection of breast cancer through mammography is effective method which detects the cancer before it is felt and increases the survival rate. In this paper, we have purposed image processing technique for enhancing the image to detect the graphical table data and markings. Texture features based on Gray-Level Co-Occurrence Matrix and intensity based features are extracted from the selected region. For classification purpose, neural network based supervised classifier system has been used which can discriminate between benign and malignant. Hence, 68 digital mammograms have been used to train the classifier. The obtained result proved that automated detection of breast cancer is beneficial for early diagnosis and increases the survival rates of breast cancer patients. The proposed system will help radiologist in the better interpretation of breast cancer.

Keywords: medical imaging, cancer, processing, neural network

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Authors: Anushaa A.

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In this work, silver nanoparticles (AgNP) were manufactured directly without harmful chemicals utilising methanol extract (SNLME) Solanum nigrume leaves. We are using nigrum leaf extract from Solanum, which converts silver nitrate to silver ions, for synthesization purposes. An examination of the AgNP produced was performed using ultraviolet (UV-VIS) spectroscopy, infrared spectroscopy (FTIR) transformed from Fourier and scanning electrons (SEM). Biological activity was also tested. UV-VIS has proven that biosynthesized AgNP exists (420-450 nm). The FTIR spectrum has been utilised to confirm the presence of different functional groups within the biomolecules, which are a nanoparticular capping agent and the spectroscopic and crystal nature of AgNP. The viability of the silver nanoparticles was evaluated using zeta potential calculations. Negative zeta potential of -33.4 mV demonstrated the stability of silver-nanoparticles. The morphology of AgNP was examined using a scanning electron microscope. Greenly generated AgNP showed significant anti-Staphylococcus aureus, Candida, and Escherichia coli action. The green AgNP demonstration indicated that the IC50 for the human teratocarcinoma cell line was 29.24 μg/ml during 24 hours of therapy (PA1 Ovarian cell line). The dose-dependent effects were reported in both antibacterial and cytotoxicity assays and as an effective agent. Finally, the findings of this research showed that silver nanoparticles generated might serve as a viable therapeutic agent to combat microorganisms killing and curing cancer.

Keywords: antimicrobial activity, PA1 ovarian cancer cell line, silver nanoparticles, Solanum nigrum

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Authors: Öznur Saribaş, Si̇bel Kahraman Çeti̇ntaş

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It is aimed to compare target volume and critical organ doses by using CyberKnife (CK) in accelerated partial breast irradiation (APBI) in patients with early stage breast cancer. Three different virtual plans were made for Iris, fixed and multi-leaf collimator (MLC) for 5 patients who received radiotherapy in the CyberKnife system. CyberKnife virtual plans were created, with 6 Gy per day totaling 30 Gy. Dosimetric parameters for the three collimators were analyzed according to the restrictions in the NSABP-39/RTOG 0413 protocol. The plans ensured critical organs were protected and GTV received 95 % of the prescribed dose. The prescribed dose was defined by the isodose curve of a minimum of 80. Homogeneity index (HI), conformity index (CI), treatment time (min), monitor unit (MU) and doses taken by critical organs were compared. As a result of the comparison of the plans, a significant difference was found for the duration of treatment, MU. However, no significant difference was found for HI, CI. V30 and V15 values of the ipsi-lateral breast were found in the lowest MLC. There was no significant difference between Dmax values for lung and heart. However, the mean MU and duration of treatment were found in the lowest MLC. As a result, the target volume received the desired dose in each collimator. The contralateral breast and contralateral lung doses were the lowest in the Iris. Fixed collimator was found to be more suitable for cardiac doses. But these values did not make a significant difference. The use of fixed collimators may cause difficulties in clinical applications due to the long treatment time. The choice of collimator in breast SBRT applications with CyberKnife may vary depending on tumor size, proximity to critical organs and tumor localization.

Keywords: APBI, CyberKnife, early stage breast cancer, radiotherapy.

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Authors: Jasminka Mujic, Karin Milde-Langosch, Volkmar Mueller, Mirza Suljagic, Tea Becirevic, Jozo Coric, Daria Ler

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MACC1 (metastasis associated in colon cancer-1) is a prognostic biomarker for tumor progression, metastasis, and survival of a variety of solid cancers. MACC1 also causes tumor growth in xenograft models and acts as a master regulator of the HGF/MET signaling pathway. In breast cancer, the expression of MACC1 determined by immunohistochemistry was significantly associated with positive lymph node status and advanced clinical stage. The aim of the present study was to further investigate the prognostic or predictive value of MACC1 expression in breast cancer using western blot analysis and immunohistochemistry. The results of our study have shown that high MACC1 expression in breast cancer is associated with shorter disease-free survival, especially in node-negative tumors. The MACC1 might be a suitable biomarker to select patients with a higher probability of recurrence which might benefit from adjuvant chemotherapy. Our results support a biologic role and potentially open the perspective for the use of MACC1 as predictive biomarker for treatment decision in breast cancer patients.

Keywords: breast cancer, biomarker, HGF/MET, MACC1

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Authors: Amir Saber Gharamaleki, Beitollah Alipour, Zeinab Faghfoori, Ahmad YariKhosroushahi

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Colorectal cancer (CRC) is one of the most prevalent cancers and intestinal microbial community plays an important role in colorectal tumorigenesis. Probiotics have recently been assessed as effective anti-proliferative agents and thus this study was performed to examine whether CRC undergo apoptosis by treating with isolated Iranian native dairy yeast, Kluyveromyces marxianus YAS, secretion metabolites. The cytotoxicity assessments on cells (HT-29, Caco-2) were accomplished through 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay as well as qualitative DAPI (4',6-diamidino-2-phenylindole staining) and quantitative (flow cytometry assessments) evaluations of apoptosis. To evaluate the main mechanism of apoptosis, Real time PCR method was applied. Kluyveromyces marxianus YAS secretions (IC50) showed significant cytotoxicity against HT-29 and Caco-2 cancer cell lines (66.57 % and 66.34 % apoptosis) similar to 5-Fluorouracil (5-FU) while apoptosis only was developed in 27.57 % of KDR normal cells. The prophylactic effects of Kluyveromyces marxianus (PTCC 5195), as a reference yeast, was not similar to Kluyveromyces marxianus YAS indicating strain dependency of bioactivities on CRC disease prevention. Based on real time PCR results, the main cytotoxicity is related to apoptosis phenomenon and the core related mechanism is depended on the overexpression of BAX, CASP 9, CASP 8 and CASP 3 inducing apoptosis genes. However, several investigations should be conducted to precisely determine the effective compounds to be used as anticancer therapeutics in the future.

Keywords: anticancer, anti-proliferative, apoptosis, cytotoxicity, yeast

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Authors: Yingjeng James Li, Lung-Yu Sung, Huan-Jyun Ciou

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Durability of Membrane Electrode Assembly for Proton Exchange Membrane Fuel Cells was evaluated in both steady state and accelerated decay modes. Steady state mode was carried out at constant current of 800mA / cm2 for 2500 hours using air as cathode feed and pure hydrogen as anode feed. The degradation of the cell voltage was 0.015V after such 2500 hrs operation. The degradation rate was therefore calculated to be 6uV / hr. Accelerated mode was carried out by switching the voltage of the single cell between OCV and 0.2V. The durations held at OCV and 0.2V were 20 and 40 seconds, respectively, meaning one minute per cycle. No obvious change in performance of the MEA was observed after 10000 cycles of such operation.

Keywords: durability, lifetime, membrane electrode assembly, proton exchange membrane fuel cells

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Authors: Neha Singh

Abstract:

Background: Nowadays, the nanoparticle is gaining unexceptional attention in targeted drug delivery. But before proceeding to this episode of accomplishment, the journey and closure of these nanoparticles inside the cells should be disentangle. Being foreign for the cells, nanoparticles will easily getcleared off without any effective outcome. As the cancer cells withhold these nanoparticles for a longer period of time, more will be the drug’s effect. Chlorpromazine is a cationic amphiphilic drug which is believed to inhibit clathrin-coated pit formation by a reversible translocation of clathrin and its adapter proteins from the plasma membrane to intracellular vesicles. Chlorpromazine has a role in increasing the retention of nanoparticles in cancer cells. The mechanism of action how this small molecule increases the retention of nanoparticles is still uncovered. Method: Polymeric nanoparticle (PLGA) with Cyanine3.5 dye were synthesized by solvent evaporation method and characterized for size and zeta potential. FTIR was also done. Pulse and chase studies with and without inhibitor were done to check the retention of nanoparticle using fluorescence microscopy. Mean fluorescence intensity was measured by ImageJ software. Results: Increased retention of nanoparticle with inhibitor was observed in both pulse and chase studies. Conclusion: Our results demonstrate that by repurposing these small molecule inhibitor, we can increase the retention of nanoparticle at the targeted site.

Keywords: nanoparticle, endocytosis, clathrin inhibitor, cancer cell

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Authors: Ragini Verma, J. Ponmozhi

Abstract:

The oral cavity is home to a wide variety of microorganisms that lead to various diseases and even oral cancer. Despite advancements in the diagnosis and detection at the initial phase, the situation hasn’t improved much. Saliva-on-a-chip is an innovative point-of-care platform for early diagnosis of oral cancer and other oral diseases in live and dead cells using a microfluidic device with a current perspective. Some of the major challenges, like real-time imaging of the oral cancer microbes, high throughput values, obtaining a high spatiotemporal resolution, etc. were faced by the scientific community. Integrated microfluidics and microscopy provide powerful approaches to studying the dynamics of oral pathology, microbe interaction, and the oral microenvironment. Here we have developed a saliva-on-chip (salivary microbes) device to monitor the effect on oral cancer. Adhesion of cancer-causing F. nucleatum; subsp. Nucleatum and Prevotella intermedia in the device was observed. We also observed a significant reduction in the oral cancer growth rate when mortality and morbidity were induced. These results show that this approach has the potential to transform the oral cancer and early diagnosis study.

Keywords: microfluidic device, oral cancer microbes, early diagnosis, saliva-on-chip

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

Abstract:

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

Keywords: ALDH1A1, BPH, PIN, prostatic adenocarcinoma

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Authors: Shenghui Wu, Patricia Chalela, Amelie G. Ramirez

Abstract:

Background: Cervical cancer (CC), colorectal cancer (CRC), and breast cancer (BC) are diseases that can be prevented/detected through early test. Through educational programs, individuals can become better informed about these cancers and understand the importance of screening and early detection. A community-based educational program was developed to improve knowledge and awareness toward the screening of the three cancer types in a South Texas underserved population. Methods: Residents living in Laredo, Texas were invited to participate in the present study. From January 2020 to April 2021, participants were recruited using social media and flyer distributions in general community. Participants received a free live web cancer education presentation delivered by bilingual community health educators, and online pre- and post-education surveys for CC, CRC, and BC separately. Pre-post changes in knowledge for individual items were compared using McNemar’s chi-squared tests. Results: Overall, participants demonstrated increases in CC (n=237), CRC (n=59), and BC (n=56) screening knowledge and awareness after receiving the cancer screening education (Ps<0.05). After receiving the cancer screening education, 85-97% of participants had an intent to talk to a healthcare provider about CC/CRC/BC screening, 88-97% had an intent to get a CC/CRC/BC screening test in the next 12 months or at the next routine appointment, and 90-97% had an intent to talk about CC/CRC/BC with their family members or friends. Conclusion: A community-based educational program can help increase knowledge and awareness about cervical, colorectal, and breast cancer screening, promote positive changes in population's knowledge and awareness about the benefits of cancer screening.

Keywords: cervical cancer, colorectal cancer, breast cancer, educational program, health knowledge, awareness, Hispanics, screening, health education

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Authors: Jyothi Nagraj, Sudeshna Mukherjee, Rajdeep Chowdhury

Abstract:

Autophagy has recently been linked with cancer cell survival post drug insult contributing to acquisition of resistance. However, the molecular signaling governing autophagic survival response is poorly explored. In our study, in osteosarcoma (OS) cells cisplatin shock was found to activate both MAPK and autophagy signaling. An activation of JNK and autophagy acted as pro-survival strategy, while ERK1/2 triggered apoptotic signals upon cisplatin stress. An increased sensitivity of the cells to cisplatin was obtained with simultaneous inhibition of both autophagy and JNK pathway. Furthermore, we observed that the autophagic stimulation upon drug stress regulates other developmentally active signaling pathways like the Hippo pathway in OS cells. Cisplatin resistant cells were thereafter developed by repetitive drug exposure followed by clonal selection. Basal levels of autophagy were found to be high in resistant cells to. However, the signaling mechanism leading to autophagic up-regulation and its regulatory effect differed in OS cells upon attaining drug resistance. Our results provide valuable clues to regulatory dynamics of autophagy that can be considered for development of improved therapeutic strategy against resistant type cancers.

Keywords: JNK, autophagy, drug resistance, cancer

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Authors: Sanjeewa Seneviratne, Ian Campbell, Nina Scott, Ross Lawrenson

Abstract:

Introduction: Indigenous Māori women experience a 60% higher breast cancer mortality rate compared with European women in New Zealand. We explored the impact of difference in the rate of screen detected breast cancer between Māori and European women on more advanced disease at diagnosis and lower survival in Māori women. Methods: All primary in-situ and invasive breast cancers diagnosed in screening age women (as defined by the New Zealand National Breast Cancer Screening Programme) between 1999 and 2012 in the Waikato area were identified from the Waikato Breast Cancer Register and the national screening database. Association between screen versus non-screen detection and cancer stage at diagnosis and survival were compared by ethnicity and socioeconomic deprivation. Results: Māori women had 50% higher odds of being diagnosed with more advance staged cancer compared with NZ European women, a half of which was explained by the lower rate of screen detected cancer in Māori women. Significantly lower breast cancer survival rates were observed for Māori compared with NZ European and most deprived compared with most affluent socioeconomic groups for symptomatically detected breast cancer. No significant survival differences by ethnicity or socioeconomic deprivation were observed for screen detected breast cancer. Conclusions: Low rate of screen detected breast cancer appears to be a major contributor for more advanced stage disease at diagnosis and lower breast cancer survival in Māori compared with NZ European women. Increasing screening participation for Māori has the potential to substantially reduce breast cancer mortality inequity between Māori and NZ European women.

Keywords: breast cancer, screening, ethnicity, inequity

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Authors: Feng-Sheng Wang, Chao-Ting Cheng

Abstract:

Developing a drug from conception to launch is costly and time-consuming. Computer-aided methods can reduce research costs and accelerate the development process during the early drug discovery and development stages. This study developed a fuzzy multi-objective hierarchical optimization framework for identifying potential anticancer targets in a metabolic model. First, RNA-seq expression data of colorectal cancer samples and their healthy counterparts were used to reconstruct tissue-specific genome-scale metabolic models. The aim of the optimization framework was to identify anticancer targets that lead to cancer cell death and evaluate metabolic flux perturbations in normal cells that have been caused by cancer treatment. Four objectives were established in the optimization framework to evaluate the mortality of cancer cells for treatment and to minimize side effects causing toxicity-induced tumorigenesis on normal cells and smaller metabolic perturbations. Through fuzzy set theory, a multiobjective optimization problem was converted into a trilevel maximizing decision-making (MDM) problem. The applied nested hybrid differential evolution was applied to solve the trilevel MDM problem using two nutrient media to identify anticancer targets in the genome-scale metabolic model of colorectal cancer, respectively. Using Dulbecco’s Modified Eagle Medium (DMEM), the computational results reveal that the identified anticancer targets were mostly involved in cholesterol biosynthesis, pyrimidine and purine metabolisms, glycerophospholipid biosynthetic pathway and sphingolipid pathway. However, using Ham’s medium, the genes involved in cholesterol biosynthesis were unidentifiable. A comparison of the uptake reactions for the DMEM and Ham’s medium revealed that no cholesterol uptake reaction was included in DMEM. Two additional media, i.e., a cholesterol uptake reaction was included in DMEM and excluded in HAM, were respectively used to investigate the relationship of tumor cell growth with nutrient components and anticancer target genes. The genes involved in the cholesterol biosynthesis were also revealed to be determinable if a cholesterol uptake reaction was not induced when the cells were in the culture medium. However, the genes involved in cholesterol biosynthesis became unidentifiable if such a reaction was induced.

Keywords: Cancer metabolism, genome-scale metabolic model, constraint-based model, multilevel optimization, fuzzy optimization, hybrid differential evolution

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