Selected Papers in the 1st International Electronic Conference on Biomedicine (ECB 2021)

A special issue of Biomedicines (ISSN 2227-9059). This special issue belongs to the section "Molecular and Translational Medicine".

Deadline for manuscript submissions: closed (31 December 2021) | Viewed by 30440

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1. Retired, The Pharmaceutical Research Institute, Albany College of Pharmacy and Health Sciences, 1 Discovery Drive (Room 238), Rensselaer, NY 12144, USA
2. Vascular Vision Pharmaceuticals Co., Rensselaer Polytechnic Park, Troy, NY 12180, USA
Interests: pharmaceuticals; biopharmaceuticals and diagnostics; nanomedicine; cardiovascular diseases; neurological disorders; hematology and oncology; biosimilar and nanosimilar; angiogenesis; inflammation; thrombosis; integrin and cell adhesion molecules; target identification; molecular mechanisms and signaling pathways; preclinical; clinical; marketing and post marketing studies; regulatory and ethical issues
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Department of Surgery, University of Pittsburgh School of Medicine, and University of Pittsburgh Cancer Institute, Pittsburgh, PA 15213, USA
Interests: oncolytic virus; cancer immunotherapy; oncolytic vaccine; therapeutic cancer vaccine; viro-immunotherapy; immunovirotherapy; gene therapy; vaccinia virus
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1. NF-kB, Differenciation and Cancer, University Paris Descartes, Sorbonne Paris Cité, 75014 Paris, France
2. Faculté de Pharmacie, 4 Avenue de l'Observatoire, 75006 Paris, France
Interests: interface between signal transduction and cancer with a focus on the alternative NF-kappaB signaling pathway, how it is regulated, and its contributions towards tumor development and resistance to conventional cancer therapies
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Department of Pathology and Molecular Medicine, McMaster University, Hamilton, ON L8S 4K1, Canada
Interests: neuroprotective therapies in neurotrauma; neuroregeneration in spinal cord injury; new, improved models of cancer and other human diseases

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Department of Surgery, University of Pittsburgh School of Medicine, and University of Pittsburgh Cancer Institute, Pittsburgh, PA 15213, USA
Interests: oncolytic virus; cancer immunotherapy; oncolytic vaccine; therapeutic cancer vaccine; viro-immunotherapy; immunovirotherapy; gene therapy; vaccinia virus
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School of Chemical Sciences, University of Auckland, Private Bag 92019, Auckland 1142, New Zealand
Interests: anticancer agents; metals in medicine; Medicinal bioinorganic chemistry; drug delivery; antibacterial agents; metal complexes

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Nanotechnology and Regenerative Medicine, The London BioScience Innovation Centre, London NW1 0NH, UK
Interests: graphene nanoparticle; human organs; 3D scaffold; 3D bioprinter; stem cells; nanocomposite materials
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Neuroscience Research Group, Hungarian Research Network, Danube Neuroscience Research Laboratory, University of Szeged (HUN-REN-SZTE), Szeged, Hungary
Interests: neurohormones; neuropeptides; tryptophan; kynurenine; psychiatry; neurology; depression; anxiety; dementia; cognition; antidepressant; translational research
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Special Issue Information

ECB 2021 will present the latest research related to all aspects of research on human health and disease, the discovery and characterisation of new therapeutic targets, therapeutic strategies, and research of naturally driven biomedicines, pharmaceuticals, and biopharmaceutical products.

Topics of interest include but are not limited to:

    Nanomedicine and precision medicine

    Nutraceuticals, nano nutraceuticals, and nano pharmaceuticals

    Cancer therapeutics

    Metal-based therapeutics in preclinical and clinical developments

    Oncolytic virus-mediated immunotherapy

    Neuroprotective therapies in spinal cord injury; the first and necessary step towards the cure

    Exploring biomedicines in behavioral neurology and neuropsychiatry

    Nanomaterials and its application in biomedicine, including drug/gene/vaccine delivery, imaging, medical devices, and surgical implants

    Translational biomarkers in clinical biomedicine and precision medicine

    G-protein-coupled receptor family

    Microbiota, probiotics, and nutraceuticals: preventive and therapeutic potential

ECB 2021 is an electronic conference sponsored by Biomedicines. Participation is free of charge for authors and attendees. Accepted papers will be gathered in the proceedings of the conference. Selected extended versions of the papers will be published in a Special Issue of Biomedicines and undergo full peer review (ISSN 2227-9059; impact factor: 4.717 (2020)) with a 20% discount on the article processing charge. ECB 2021 offers you the opportunity to participate in this international, scholarly conference without the concerns or expenditure of travel—all you need is your computer and access to the internet. We would like to invite you to attend this conference and present your latest work.

Prof. Dr. Shaker Mousa
Dr. Zong Sheng Guo
Dr. Veronique Baud
Prof. Dr. Ciro Isidoro
Assoc. Pro Jacek M. Kwiecien
Dr. Ujendra Kumar
Dr. David L. Bartlett
Dr. Allan Stensballe
Dr. Muhammad Hanif
Prof. Dr. Alexander Seifalian
Dr. Masaru Tanaka
Guest Editors

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Keywords

  • nanotechnology
  • biotechnology
  • nutraceuticals
  • pharmaceuticals/biopharmaceuticals
  • personalised medicines and emerging technologies in discovery and development
  • nanomaterials
  • graphene
  • drug delivery
  • vaccine delivery
  • gene delivery
  • nanoparticles
  • stem cells
  • cancer
  • metabolism
  • immunotherapy
  • nanotechnology
  • antidepressant
  • analgesic
  • antipsychotic
  • neuroprotection

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Published Papers (8 papers)

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Research

16 pages, 11443 KiB  
Article
Resveratrol and Its Analogue 4,4′-Dihydroxy-trans-stilbene Inhibit Lewis Lung Carcinoma Growth In Vivo through Apoptosis, Autophagy and Modulation of the Tumour Microenvironment in a Murine Model
by Monica Savio, Alessandra Ferraresi, Chiara Corpina, Sara Vandenberghe, Chiara Scarlata, Virginie Sottile, Luca Morini, Beatrice Garavaglia, Ciro Isidoro and Lucia Anna Stivala
Biomedicines 2022, 10(8), 1784; https://doi.org/10.3390/biomedicines10081784 - 25 Jul 2022
Cited by 11 | Viewed by 2586
Abstract
Lung cancer is the most prevalent cancer worldwide. Despite advances in surgery and immune-chemotherapy, the therapeutic outcome remains poor. In recent years, the anticancer properties of natural compounds, along with their low toxic side effects, have attracted the interest of researchers. Resveratrol (RSV) [...] Read more.
Lung cancer is the most prevalent cancer worldwide. Despite advances in surgery and immune-chemotherapy, the therapeutic outcome remains poor. In recent years, the anticancer properties of natural compounds, along with their low toxic side effects, have attracted the interest of researchers. Resveratrol (RSV) and many of its derivatives received particular attention for their beneficial bioactivity. Here we studied the activity of RSV and of its analogue 4,4′-dihydroxystilbene (DHS) in C57BL/6J mice bearing cancers resulting from Lung Lewis Carcinoma (LLC) cell implantation, considering tumour mass weight, angiogenesis, cell proliferation and death, autophagy, as well as characterization of their immune microenvironment, including infiltrating cancer-associated fibroblasts (CAFs). C57BL/6J mice started treatment with RSV or DHS, solubilised in drinking water, one week before LLC implantation, and continued for 21 days, at the end of which they were sacrificed, and the tumour masses collected. Histology was performed according to standard procedures; angiogenesis, cell proliferation and death, autophagy, infiltrating-immune cells, macrophages and fibroblasts were assessed by immunodetection assays. Both stilbenic compounds were able to contrast the tumour growth by increasing apoptosis and autophagy in LLC tumour masses. Additionally, they contrasted the tumour-permissive microenvironment by limiting the infiltration of tumour-associated immune-cells and, more importantly, by counteracting CAF maturation. Therefore, both stilbenes could be employed to synergise with conventional oncotherapies to limit the contribution of stromal cells in tumour growth. Full article
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22 pages, 5020 KiB  
Article
Butyrate Inhibits Colorectal Cancer Cell Proliferation through Autophagy Degradation of β-Catenin Regardless of APC and β-Catenin Mutational Status
by Beatrice Garavaglia, Letizia Vallino, Alessandra Ferraresi, Andrea Esposito, Amreen Salwa, Chiara Vidoni, Sergio Gentilli and Ciro Isidoro
Biomedicines 2022, 10(5), 1131; https://doi.org/10.3390/biomedicines10051131 - 13 May 2022
Cited by 21 | Viewed by 5620
Abstract
Colorectal cancer (CRC) pathogenesis is mainly driven by alterations in WNT signaling, which results in altered transcriptional activity of β-Catenin. Mutations in APC (Adenomatous Polyposis Coli) are reflected in β-Catenin hyperactivation and loss of proliferation control. Certain intestinal bacteria metabolites have shown the [...] Read more.
Colorectal cancer (CRC) pathogenesis is mainly driven by alterations in WNT signaling, which results in altered transcriptional activity of β-Catenin. Mutations in APC (Adenomatous Polyposis Coli) are reflected in β-Catenin hyperactivation and loss of proliferation control. Certain intestinal bacteria metabolites have shown the ability to limit CRC cell proliferation and CRC pathogenesis. Here, we investigated the molecular mechanism underlying the anti-proliferative activity of butyrate, a microbiota-derived short chain fatty acid, in two CRC cell lines, namely HCT116 and SW620, which bear a mutation in β-Catenin and APC, respectively. In particular, we focused on autophagy, a lysosome-dependent degradation pathway, which was shown to control intestinal tissue homeostasis. Butyrate reduced CRC cell proliferation, as witnessed by the downregulation of proliferation markers. TCGA bioinformatic transcriptomic analysis of CTNNB1 (β-Catenin) gene correlation in CRC patients showed that β-Catenin negatively correlates with the autophagy gene ATG4D. In CRC cells, regardless of the mutational state of APC or β-Catenin genes, butyrate caused the autophagy-mediated degradation of β-Catenin; thus, preventing its transcriptional activity. Autophagy gene silencing restored β-Catenin levels, allowing it to translocate into the nucleus to promote the expression of downstream genes associated with cancer cell proliferation. CRC-affected patients show driver mutations in the WNT pathway; thus, targeting its crucial effector may be a promising therapeutic strategy in CRC treatment; for instance, by using ad hoc probiotics that stimulate autophagy. Full article
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15 pages, 3931 KiB  
Article
Faecalibacterium prausnitzii Ameliorates Colorectal Tumorigenesis and Suppresses Proliferation of HCT116 Colorectal Cancer Cells
by Ifeoma Julieth Dikeocha, Abdelkodose Mohammed Al-Kabsi, Hsien-Tai Chiu and Mohammed Abdullah Alshawsh
Biomedicines 2022, 10(5), 1128; https://doi.org/10.3390/biomedicines10051128 - 13 May 2022
Cited by 34 | Viewed by 4215
Abstract
Faecalibacterium prausnitzii is one of the most abundant commensals of gut microbiota that is not commonly administered as a probiotic supplement. Being one of the gut’s major butyrate-producing bacteria, its clinical significance and uses are on the rise and it has been shown [...] Read more.
Faecalibacterium prausnitzii is one of the most abundant commensals of gut microbiota that is not commonly administered as a probiotic supplement. Being one of the gut’s major butyrate-producing bacteria, its clinical significance and uses are on the rise and it has been shown to have anti-inflammatory and gut microbiota-modulating properties in the treatment of inflammatory bowel illness, Crohn’s disease, and colorectal cancer. Colorectal cancer (CRC) is a silent killer disease that has become one of the leading causes of cancer-related death worldwide. This study aimed to evaluate the anti-tumorigenic and antiproliferative role of F. prausnitzii as well as to study its effects on the diversity of gut microbiota in rats. Findings showed that F. prausnitzii probiotic significantly reduced the colonic aberrant crypt foci frequency and formation in Azoxymethane (AOM)-induced CRC in rats. In addition, the administration of F. prausnitzii lowered the lipid peroxidation levels in the colon tissues. For in vitro 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl tetrazolium bromide (MTT) assay, the cell-free supernatant of F. prausnitzii suppressed the growth of HCT116 colorectal cancer cells in a time/dose-dependent manner. 16S rRNA gene sequencing using rat stool samples showed that the administration of F. prausnitzii modulated the gut microbiota of the rats and enhanced its diversity. Hence, these findings suggest that F. prausnitzii as a probiotic supplement can be used in CRC prevention and management; however, more studies are warranted to understand its cellular and molecular mechanisms of action. Full article
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18 pages, 8499 KiB  
Article
Diosmetin Exerts Synergistic Effects in Combination with 5-Fluorouracil in Colorectal Cancer Cells
by Sareh Kamran, Ajantha Sinniah, Zamri Chik and Mohammed Abdullah Alshawsh
Biomedicines 2022, 10(3), 531; https://doi.org/10.3390/biomedicines10030531 - 24 Feb 2022
Cited by 28 | Viewed by 4429
Abstract
5-Fluorouracil (5-FU) is a chemotherapeutic medication commonly used to treat colorectal cancer (CRC); however, the drug-associated adverse effects and toxicity have greatly affected its clinical use. Exploring another therapeutic strategy that lowers the toxicity of 5-FU while having a synergistic effect against CRC [...] Read more.
5-Fluorouracil (5-FU) is a chemotherapeutic medication commonly used to treat colorectal cancer (CRC); however, the drug-associated adverse effects and toxicity have greatly affected its clinical use. Exploring another therapeutic strategy that lowers the toxicity of 5-FU while having a synergistic effect against CRC is thus a viable option. Diosmetin, a natural flavonoid, has been shown to inhibit the proliferation of many cancer cells, including CRC cells. This study aims to investigate the synergistic effect of diosmetin and 5-FU on HCT116 and HT29 colorectal cancer cells and to explore the apoptotic activity of this combination. The MTT assay was used to assess the viability of cells treated with monotherapy and combination therapy. The combination index (CI) and dose reduction index (DRI) were calculated using the CompuSyn software (version 1.0). The SynergyFinder 2.0 software was used to calculate the synergy score, while the Combenefit software was employed to perform isobologram analysis and synergism determination. The AO/PI double staining technique was used to detect the apoptotic characteristics of cells, whereas the flow cytometry technique was used to investigate the apoptosis induction and cell cycle arrest in cells. The combination of 5-FU and diosmetin showed a synergistic effect in HCT116 cells with a mean CI value of 0.66 ± 0.4, and an additive effect in HT29 cells with a CI value of 1.0 ± 0.2. The DRI of 5-FU in HCT116 cells was three times lower in the combination therapy compared to monotherapy of 5-FU. AO/PI microscopic examination and Annexin V analysis revealed that the combination-treated cells had more apoptotic cells than the monotherapy-treated cells, which was activated mainly through intrinsic apoptosis pathway. HCT116 cell death was confirmed by mitotic arrest in the G2/M phase. Our findings suggest that 5-FU/diosmetin combination exhibits synergistic effect against HCT116 cancer cells, and potentially reduces the unfavorable adverse effect of 5-FU while enhancing the anticancer efficacy by inducing apoptosis and interrupting mitosis. Further research studies are needed to validate the combination’s anti-tumorigenic activities in a xenograft animal model. Full article
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14 pages, 2941 KiB  
Article
Co-Entrapment of Sorafenib and Cisplatin Drugs and iRGD Tumour Homing Peptide by Poly[ε-caprolactone-co-(12-hydroxystearate)] Copolymer
by Izolda Kántor, Diana Dreavă, Anamaria Todea, Francisc Péter, Zoltán May, Emese Biró, György Babos and Tivadar Feczkó
Biomedicines 2022, 10(1), 43; https://doi.org/10.3390/biomedicines10010043 - 26 Dec 2021
Cited by 3 | Viewed by 3044
Abstract
The drug-loaded nanocarriers have overcome various challenges compared with the pure chemotherapeutic drug, such as limited bioavailability, multiple drug resistance, poor patient compliance, and adverse drug reactions, offering advantages such as protection from degradation in the blood stream, better drug solubility, and improved [...] Read more.
The drug-loaded nanocarriers have overcome various challenges compared with the pure chemotherapeutic drug, such as limited bioavailability, multiple drug resistance, poor patient compliance, and adverse drug reactions, offering advantages such as protection from degradation in the blood stream, better drug solubility, and improved drug stability. One promising group of controlled and targeted drug delivery systems is polymer-based nanoparticles that can sustain the release of the active agent by diffusion and their degradation. Sorafenib is the only drug that can prolong the life of patients suffering from hepatocellular carcinoma. Cisplatin remains one of the most widely used broad-spectrum anticancer drugs for the treatment of a variety of solid tumours. Nanoformulations can exert a synergistic effect by entrapping two drugs with different modes of action, such as sorafenib and cisplatin. In our study, polymeric nanoparticles were prepared with a good production yield by an improved double emulsion solvent evaporation method using the copolymer of 12-hydroxystearic acid with ε-caprolactone (12CL), a biocatalytically synthesised biocompatible and biodegradable carrier, for the co-entrapment of sorafenib and cisplatin in nanotherapeutics. A bovine serum albumin (BSA) model compound was used to increase the cisplatin incorporation; then, it was successfully substituted by a iRGD tumour penetrating peptide that might provide a targeting function of the nanoparticles. Full article
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13 pages, 3325 KiB  
Article
Blood Compatibility of Amphiphilic Phosphorous Dendrons—Prospective Drug Nanocarriers
by Simon Suty, Veronika Oravczova, Zuzana Garaiova, Veronika Subjakova, Maksim Ionov, Dzmitry Shcharbin, Zuzana Simonikova, Peter Bartek, Milan Zvarik, Xiangyang Shi, Serge Mignani, Jean-Pierre Majoral, Maria Bryszewska, Tibor Hianik and Iveta Waczulikova
Biomedicines 2021, 9(11), 1672; https://doi.org/10.3390/biomedicines9111672 - 12 Nov 2021
Cited by 4 | Viewed by 2720
Abstract
Dendrons are branched synthetic polymers suitable for preparation of nanosized drug delivery systems. Their interactions with biological systems are mainly predetermined by their chemical structure, terminal groups, surface charge, and the number of branched layers (generation). Any new compound intended to be used, [...] Read more.
Dendrons are branched synthetic polymers suitable for preparation of nanosized drug delivery systems. Their interactions with biological systems are mainly predetermined by their chemical structure, terminal groups, surface charge, and the number of branched layers (generation). Any new compound intended to be used, alone or in combination, for medical purposes in humans must be compatible with blood. This study combined results from in vitro experiments on human blood and from laboratory experiments designed to assess the effect of amphiphilic phosphorous dendrons on blood components and model membranes, and to examine the presence and nature of interactions leading to a potential safety concern. The changes in hematological and coagulation parameters upon the addition of dendrons in the concentration range of 2–10 µM were monitored. We found that only the combination of higher concentration and higher generation of the dendron affected the selected clinically relevant parameters: it significantly decreased platelet count and plateletcrit, shortened thrombin time, and increased activated partial thromboplastin time. At the same time, occasional small-sized platelet clumps in blood films under the light microscope were observed. We further investigated aggregation propensity of the positively charged dendrons in model conditions using zwitterionic and negatively charged liposomes. The observed changes in size and zeta potential indicated the electrostatic nature of the interaction. Overall, we proved that the low-generation amphiphilic phosphorous dendrons were compatible with blood within the studied concentration range. However, interactions between high-generation dendrons at bulk concentrations above 10 µM and platelets and/or clotting factors cannot be excluded. Full article
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14 pages, 3922 KiB  
Article
Cancer Stem Cells and Somatic Stem Cells as Potential New Drug Targets, Prognosis Markers, and Therapy Efficacy Predictors in Breast Cancer Treatment
by Olga Pershina, Natalia Ermakova, Angelina Pakhomova, Darius Widera, Edgar Pan, Mariia Zhukova, Elena Slonimskaya, Sergey G. Morozov, Aslan Kubatiev, Alexander Dygai and Evgenii G. Skurikhin
Biomedicines 2021, 9(9), 1223; https://doi.org/10.3390/biomedicines9091223 - 14 Sep 2021
Cited by 7 | Viewed by 2679
Abstract
New drug targets, markers of disease prognosis, and more efficient treatment options are an unmet clinical need in breast cancer (BC). We have conducted a pilot study including patients with luminal B stage breast cancer IIA–IIIB. The presence and frequency of various populations [...] Read more.
New drug targets, markers of disease prognosis, and more efficient treatment options are an unmet clinical need in breast cancer (BC). We have conducted a pilot study including patients with luminal B stage breast cancer IIA–IIIB. The presence and frequency of various populations of cancer stem cells (CSC) and somatic stem cells were assessed in the blood, breast tumor tissue, and normal breast tissue. Our results suggest that patients with BC can be divided into two distinct groups based on the frequency of aldehyde dehydrogenase positive cells (ALDH1+ cells) in the blood (ALDH1hi and ALDH1low). In the ALDH1hi cells group, the tumor is dominated by epithelial tumor cells CD44+CD24low, CD326+CD44+CD24, and CD326CD49f+, while in the ALDH1low cells group, CSCs of mesenchymal origin and epithelial tumor cells (CD227+CD44+CD24 and CD44+CD24CD49f+) are predominant. In vitro CSCs of the ALDH1low cells group expressing CD326 showed high resistance to cytostatics, CD227+ CSCs of the ALDH1hi cells group are sensitive to cytostatics. Epithelial precursors of a healthy mammary gland were revealed in normal breast tissue of patients with BC from both groups. The cells were associated with a positive effect of chemotherapy and remission in BC patients. Thus, dynamic control of their presence in blood and assessment of the sensitivity of CSCs to cytostatics in vitro can improve the effectiveness of chemotherapy in BC. Full article
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14 pages, 558 KiB  
Article
Significant Implications of APOA1 Gene Sequence Variations and Its Protein Expression in Bladder Cancer
by Javid A. Magray, Arshad A. Pandith, Iqbal Qasim, Muzzain Khateeb, Arif Hamid, Aabid Koul, Zafar A. Shah, Shahid M. Baba, Sheikh Mansoor, Wafa Charifi, Ajaz Ahmad and Mohammad S. Wani
Biomedicines 2021, 9(8), 938; https://doi.org/10.3390/biomedicines9080938 - 2 Aug 2021
Cited by 5 | Viewed by 2632
Abstract
Apolipoprotein A1 (APOA1) is a potential biomarker because of its variable concentration in different types of cancers. The current study is the first of its kind to evaluate the association between the APOA1 genotypes of −75 G/A and +83 C/T in [...] Read more.
Apolipoprotein A1 (APOA1) is a potential biomarker because of its variable concentration in different types of cancers. The current study is the first of its kind to evaluate the association between the APOA1 genotypes of −75 G/A and +83 C/T in tandem with the APOA1 protein expression in urine samples to find out the risk and potential relationship for differentially expressed urinary proteins and APOA1 genotypes. The study included 108 cases of bladder tumors and 150 healthy controls that were frequency matched to cases with respect to age, sex, and smoking status. Genotyping was performed using PCR-RFLP and the urinary expression of the APOA1 protein was done using ELISA. Bladder tumor cases were significantly associated with the APOA1 −75 AA genotype (p < 0.05), while the APOA1 +83 C/T heterozygotes showed an association with cases (p < 0.05). The overall distribution of the different haplotypes showed a marked difference between the cases and controls in GT when compared with the wild type GC (p < 0.03). Bladder tumor cases that carried the variant genotype APOA1 −75AA were found more (70.0%) with a higher expression (≥20 ng/mL)of the APOA1 urinary protein and differed significantly against wild type GG (p = 0.03). Again, in low grade bladder tumors, urinary APOA1 protein was exhibited significantly more (52.4% vs. 15.4% high grade) with a higher expression (≥20 ng), while high grade tumor cases (84.6% vs. 47.5% low grade) showed a lower APOA1 expression (<20 ng/mL) (O.R = 6.08, p = 0.002). A strong association was observed between APOA1 −75G/A and risk for bladder tumor and its relation to urinary protein expression, which substantiates its possible role as a marker for the risk assessment of the disease and as a promising diagnostic marker for different grades of malignant bladder tumors. Full article
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