Neoplasms

Skin and Connective Tissue Diseases

All Conditions

Breast Neoplasms

Breast Diseases

Skin Diseases

Histopathologically confirmed primary female breast cancer patients with age group (20-70 years)

Healthy female volunteers not suffering from any disease

Nadia Hamdy, PhD

Long non-coding RNAs (lncRNAs) play an important role in different types of cancer, including breast cancer, through regulation of gene expression and epigenetic signatures. Genetic variations such as single nucleotide polymorphisms (SNPs) in lncRNAs have been found to be associated with cancer. Our aim was to provide information about the role of LINC00511 SNPs (rs11657109 or rs17780195 or rs9906859, rs4432291 and rs1558535) in breast cancer susceptibility in the Egyptian population.

1. Introduction 1.1. Background: Breast cancer (BC) is one of the most common types of cancer in women nowadays as it is estimated that 1.6 million BC cases occur around the world each year. There were approximately 500000 women die due to BC annually making it a leading cause of cancer mortality among females. It represents 23% of the total cancer cases and 14% of the cancer deaths in females. It represents 52% of BC cases and 62% of deaths in economically developing countries. In Egypt, BC is reported to be the most frequent cancer in females (38.8%) and the age adjusted rate of BC is 49.6 per 100.000 population. Breast cancer can be classified based on the hormones and HER2 status to Luminal A BC (Estrogen Receptor(ER) + , Progesterone Receptor(PR) +/- , Human epidermal growth factor receptor 2 (HER2) -) , Luminal B BC (ER+, PR+/-, HER2 +), HER2 BC (ER-, PR- and HER2+) and Triple negative BC (TNBC) (ER-, PR- and HER2-).TNBC is an aggressive cancer due to its recurrence and fewer targeted medicines. BC can become a metastatic cancer and transfer to distant organs such as bones, lung and brain, which is the cause of its incurability. Early diagnosis of the disease leads to good prognosis and increasing the survival rate. Traditional prognostic factors, such as tumor size, tumor grade, and lymph node metastasis status, are the most important prognostic factors for BC. However, including the genetic information is needed in prognosis. As a typical cancer, BC occurs because of the interaction of genetic and nongenetic factors.

   It has been reported that long non-coding RNAs (lncRNAs) play an important role in different types of cancer, including BC, through regulation of gene expression and epigenetic signatures. LncRNAs are greater than 200 nucleotides in length. LncRNAs undergo different biological actions, such as regulating RNA stability, transcriptional regulation, acting as a scaffold, RNA enhancer, miRNA sequestration and guiding protein-DNA interaction. LncRNAs are implicated in gene expression regulation at many levels, including alternative splicing, and changing of protein localization, chromatin modification, transcription, and post-transcriptional processing. Moreover, lncRNAs are involved in several hallmarks of cancer, including uncontrolled proliferation, angiogenesis, evading cell death and metastasis. It is noteworthy to mention that, abnormal expression of lncRNAs contribute significantly to cancer susceptibility and progression in BC cases.

   Long intergenic non-coding RNA 00511 (LINC00511) is a 2265 bp ncRNA and is located on chromosome 17q24. Previous studies found that it exerts an oncogenic function in many cancers, such as BC, non-small cell lung cancer, ovarian cancer and glioma. In BC cases, being oncogenic, LINC00511 promotes tumor growth by accelerating the G1/S transition and inhibiting apoptosis. It has been demonstrated that there is an association between LINC00511 and BC growth and invasion, where competitive binding between LINC00511 and the microRNA-185 (miR-185) affects BC prognosis and progression. LINC00511 sponges miR-185-3p preventing this miRNA from binding to its target mRNA, hence, free mRNA is there, with more expression of the transcription factor E2F1, which eventually, promotes BC proliferation and progression.

   Genetic variations such as single nucleotide polymorphisms (SNPs) in lncRNAs have been found to be associated with cancer. They affect the function of target genes, through the alteration of the process of splicing and stability of mRNA conformation, leading to the modification of their downstream interacting partners. Mutant variants can affect the expression and secondary structure of lncRNAs, which may affect the status of the binding site(s) for miRNAs, furthermore, altering the interaction between miRNAs and mRNAs. SNPs in lncRNAs may increase or reduce the risk of cancer, depending on the function of lncRNA, as it may act as oncogene or tumor suppressor gene, a hypothesis to be explored. Moreover, SNPs in lncRNAs may increase or reduce the risk of cancer, depending on the location of these SNPs, if in a noncoding area or not. Identifying such loci, if mutant or not, involved in BC progression or prevention, will be an important issue for understanding BC pathogenesis as well as for discovering new targets for cancer diagnosis, prevention, and/or treatment.

   1.2 Aim of the Work Providing information about the role of LINC00511 SNPs (rs11657109 or rs17780195 or rs9906859, rs4432291 and rs1558535) in BC susceptibility.

   1.3 Previous Studies Findings Chong et al. found that there was an association between LINC00511 SNPs and BC in the Chinese population. we studied the same associations but in our Egyptian population.
2. Subjects 2.1 Ethics Statement An ethical approval was obtained from Ain Shams University, Faculty of Pharmacy's review board Research Ethical Committee approval (REC ID 6, date: November 11, 2020). The study was conducted in accordance to the Declaration of Helsinki Guidelines. A written informed consent was taken from all participants.

   2.2 Power Analysis and Sample Size Calculations Sample size calculation was done using PS: Power and Sample Size Calculations software, version 3.0.11 for MS Windows (William D. Dupont and Walton D., Vanderbilt University, Nashville, Tennessee, USA). The α-error level was fixed at 0.05, the power was set at 80%. The minimum optimum sample size should be 85 participants for each SNP group.

   2.3 Study participants Will be Classified into two main groups
   * Cases group n= 267, BC female patients from National cancer institute (NCI), Cairo, Egypt.
   * Controls group n= 150, healthy female volunteers. Clinical data was obtained from medical records and the original pathology reports. The following data parameters were recorded and assessed: age of the patient, tumor size (defined by mammography or magnetic resonance techniques diameter (mm or cm) on diagnosis), initial tumor stage, BIRADs classification according to the American College of Radiology and nodal status according to the TNM classification of American Joint Committee on Cancer (AJCC).
3. Methods 3.1 Blood sampling Blood samples (5 ml) were collected from controls and BC patients, on EDTA anticoagulant vacutainers and stored at -20º C until biochemical assessment.

3.2 Biochemical Assessment was performed in the pharmacology and Biochemistry Department Lab at the Faculty of Pharmacy, The British University in Egypt and Advanced biochemistry research lab at the faculty of pharmacy, Ain Shams University.

3.3 DNA Extraction A DNA Extraction Kit (QIAamp DNA Blood Mini Kit) (Cat. No. 51104; Zymo Research, USA) was used to extract DNA from whole blood collected on EDTA anticoagulant vacutainers, according to the manufacturer's instructions.

3.4 DNA Quantification It was done using a Quawell UV-Vis spectrophotometer Q5000 (USA). 3.5 SNPs Genotyping TaqMan® SNP genotyping assay was used to perform genotyping for LINC00511 polymorphisms (rs11657109 or rs17780195 or rs9906859 or rs4432291 and rs1558535) through using the TaqMan Universal Master Mix No UNG (Thermo Fisher Scientific, USA) and StepOnePlus™ qPCR system (Applied Biosystems, USA).

3.6 Statistical analysis Statistical Package for the Social Sciences (SPSS) v.23.0 software and SHEsis software were used to perform all statistical analyses. Student's t-test and χ 2 test were used to compare quantitative and qualitative variables between cases and control groups, respectively. Logistic regression was applied to find out the association between LINC00511 SNPs and BC susceptibility. A stratified analysis was applied to further investigate the relationship between LINC00511 SNPs and BC susceptibility. To find out more about the relationship between BC susceptibility and LINC00511 SNPs, a stratified analysis was used. SHEsis software was used to do the haplotype analysis to test the combined effect of the studied SNPs.

Analyses with P value less than or equal to 0.05 were considered statistically significant.

Five milliliters of blood were collected from controls and BC patients into EDTA anticoagulant vacutainers and stored at -20º C until biochemical assessment.

Female cases and controls to find out the association of their data with female breast cancer.

Association of SNPs in Long Intergenic Noncoding RNA 00511 (LINC00511) With Breast Cancer Among the Egyptian Population

Studying the Association of Genetic Variations in Long Intergenic Noncoding RNA 00511 (LINC00511) With Breast Cancer Among the Egyptian Population

By collecting patients' data in an excel file and performing appropriate statistical analysis

British University In Egypt

Ain Shams University

Professor

Respiratory Tract (Lung and Bronchial) Diseases

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Symptoms and General Pathology

Digestive System Diseases

Heart and Blood Diseases

Immune System Diseases

Lung Neoplasms

Carcinoma

Prostatic Neoplasms

Inflammation

Carcinoma, Hepatocellular

Thromboembolism

Thrombosis

Embolism

Embolism and Thrombosis

Vascular Diseases

All Drugs and Chemicals

Anticoagulants

Antineoplastic Agents

Coagulants

Anti-Infective Agents

Amino Acids

Immunomodulating Agents

Rivaroxaban

Palbociclib

Factor Xa Inhibitors

Antithrombins

Antithrombin III

Protease Inhibitors

Serine Proteinase Inhibitors

HIV Protease Inhibitors

Enzyme Inhibitors

Protein Kinase Inhibitors

Serine

Cancer patients without any incidence of thromboembolism will be included if they are non-carriers of the targeted gene-related polymorphism (GRP).

Cancer patients without any incidence of thromboembolism will be included if they are carriers of the targeted gene-related polymorphism.

Cancer patients with incidence of thromboembolism will be included if they are carriers of the targeted gene-related polymorphism.

Cancer patients with incidence of thromboembolism will be included if they are carriers of the targeted gene-related polymorphism and will be subjected to Palbociclib treatment.

Cancer patients with incidence of thromboembolism will be included if they are carriers of the targeted gene-related polymorphism and will be subjected to anti-coagulant treatment.

Palbociclib will be administered at a dose of 125 mg oral on a 21/7 cycle.

Rivaroxaban will be administered at a dosage of 15 mg intravenously twice a day for 21 days, followed by 20 mg once daily for the subsequent 21 days.

diagnostics of patients' carriers or not of the risk allele(s)

Nehman Makdissy, Professor

Malak Naboulsi, MD

David Wehbe, MD

Samar Hamoui, PhD

Fida Ayoubi, PhD

Noha Ibrahim, PhD

Nadine Ghotme, PhD

Christelle Rahme, MD, MSc

Elisa Makdessi, MSc

Bassam Bou Deleh, MSc

Joelle Moustafa, MSc

Maria Mouawad, MSc

This study aims to assess biomarkers and their related polymorphisms in the context of cancer-associated thromboembolism, with a particular focus on their interaction with the immune system. The roles of immune checkpoints, inflammatory and angiogenesis factors, as well as circulating immune cells will be elucidated. Additionally, our investigation extends to the exploration of long non-coding RNAs (LncRNAs) and genes associated with the coagulation vascular system. Initially, these aspects will be evaluated in the context of colorectal cancer, with the intention to expand our research to other solid tumors.

The identification of these biomarkers and genetic factors holds the potential to revolutionize therapeutic approaches for patients with cancer-associated thromboembolism, shedding light on their chemotherapy resistance. The effectiveness of combining immunotherapy with targeted inhibitors like Palbociclib and anticoagulants such as Rivaroxaban, among other potential interventions, will be assessed.

This study aims to make significant contributions to the understanding of these critical aspects, ultimately leading to the development of more effective treatment strategies for cancer patients.

Cancer, especially solid tumors, remains a significant global health challenge despite ongoing advancements in risk factor identification and targeted therapies. Among the various complexities of cancer treatment, the relationship between cancer and thromboembolism, characterized by arterial and venous thrombosis, has attracted attention due to its significant impact on patient outcomes.

Cancer cells activate the coagulation system, leading to prothrombotic disorders in the vascular wall and promoting tumor progression. Patients with cancer, particularly those undergoing systemic chemotherapy, face an increased risk of thromboembolism due to abnormal blood clotting mechanisms.

Recent research has emphasized the importance of identifying novel biomarkers for risk assessment, prognosis determination, and treatment selection in cancer. Among these biomarkers, long non-coding RNAs (LncRNAs) and those of the vascular coagulation system have emerged as pivotal players in cancer development and progression. However, their role as prognostic and predictive biomarkers for cancer risk and treatment response remains relatively unexplored.

Understanding the complex interplay between cancer, immune responses, and thromboembolism is crucial. Immunological subsets, including central immune effector T cells (CD8+, CD25+), NK cells, and macrophages, have been linked to cancer prognosis. Furthermore, therapies that modulate the immune system, such as immunotherapy and cell-based therapies, hold promise for improving cancer treatment outcomes.

Most notably, these therapies exhibit immunomodulatory effects, triggering immunogenic cell death and preventing immunosuppression. However, their efficacy may be compromised in cases of cancer associated with clotting abnormalities within the circulatory system. Progenitor cells, including stem cells and endothelial progenitor cells (EPCs), are emerging as potential players in cancer therapy, offering new avenues for research.

Among the innovative approaches is the assessment of circulating immune and endothelial progenitor cells (termed "CIEs"), which may play significant roles in the mechanisms underlying cancer-associated thromboembolism. Understanding the relationship between these cells, inflammatory and angiogenic factors, immune checkpoint, and cancer progression could pave the way for improved cancer risk assessment and treatment strategies.

This study seeks to contribute to our understanding of the intricate connections between LncRNA, coagulation-related biomarkers, thromboembolism, immune responses, and cancer, using solid tumors as a representative example. By shedding light on these complex interactions, this study aims to identify potential biomarkers that can guide risk assessment and treatment decisions, ultimately improving the management of cancer patients.

Exploring Cancer-Associated Thromboembolism Prognosis Biomarkers and Polymorphisms

Unveiling Prognosis Cancer-Associated Thromboembolism Biomarkers and Their Related Polymorphisms: Exploring Their Involvement With Immune Circulating Cells and Therapeutic Reversibility

The outcome measure of VTE including DVT, PE, and other thromboembolic events will be assessed by : (1) Clinical Assessment: Clinical symptoms such as swelling and pain in the lower limbs, tenderness behind the lower leg and/or medial thigh, and supplementary evaluation with color ultrasound of the veins in both lower limbs (lower extremity venography); (2) Imaging: CT pulmonary arteriography (CTPA) will be employed in conjunction with related clinical manifestations such as dyspnea and shortness of breath for diagnosing PE; (3) Laboratory Criteria: Diagnostic criteria will also consider laboratory parameters, including elevated D-dimer levels (\> 1000 ng/mL), increased fibrinogen levels (\> 700 mg/dL), and shortened activated partial thromboplastin time (aPTT) (\< 20 sec).

The assessment of cancer progression will be conducted using the standardized TNM staging system and applying the Response Evaluation Criteria (RECIST) guideline (ver. 1.1). Clinical parameters, laboratory tests indicative of cancer progression (including tumor markers and histopathological analysis), and relevant imaging modalities (e.g., CT, MRI, or PET scans) will be employed to evaluate the extent of primary tumor growth, lymph node involvement, and the presence of distant metastases. Progression-Free Survival (PFS), a key primary clinical endpoint for assessing cancer progression, will be calculated as the duration (in months) from the date of enrollment in the study until the tumor progresses, new lesions appear, or until the participant's death from any cause. Cancer progression will be determined based on RECIST guidelines, considering an increase in tumor size or the appearance of new lesions according to imaging assessments and clinical evaluations.

The objective of this outcome is to identify and characterize novel biomarkers associated with thromboembolism and cancer progression. Specifically, the assessment will focus on Long Non-Coding RNAs (LncRNAs) such as CDKN2B and CDKN2B-AS1, and markers related to the vascular coagulation system including ACE, PAI-1, FXIII, and Prothrombin. This identification process will involve collecting biological samples (e.g., blood, tissue) from enrolled patients at the time of study enrollment. The assessment will analyze and evaluate the expression and polymorphisms of the studied genes (CDKN2B, CDKN2B-AS1, ACE, PAI-1, FXIII, and Prothrombin) using quantitative PCR (qPCR), with Ct (Cycle threshold) as the common unit of measure for all genes. This comprehensive assessment aims to enhance our understanding of the molecular signatures linked to thromboembolism and cancer progression, illuminating potential diagnostic and therapeutic avenues for improved patient outcomes.

This primary outcome assesses treatment response in patients undergoing Palbociclib therapy for controlling cancer progression and thromboembolism. The evaluation will employ RECIST criteria to measure the percentage change in tumor size, indicative of treatment effectiveness.

Analysis of overall survival and progression-free survival rates among groups

The objective of this secondary outcome is to examine genetic variants, with a specific focus on the rs1333049 G\>C polymorphism within the CDKN2B-AS1 gene. The screening for polymorphism(s) will be determined by genotyping analysis using TaqMan PCR-based genotyping for SNP identification.

Monitoring and reporting of adverse events related to the Palbociclib and Rivaroxaban treatment regimen.

This outcome aims to comprehensively assess immune cell populations involved in the immune response, including T cells, B cells, natural killer (NK) cells, dendritic cells (DCs), and macrophages. The objective is to characterize changes in immune cell subsets over time, providing insights into the immune response dynamics. The assessment will involve immunophenotyping using flow cytometry to quantify and analyze the different immune cell populations. The unit of measure for this assessment will be the percentage of change of T cells, B cells, NK cells, DCs, and macrophages in the total population. The percentage of change will be determined up to a period of 60 months relatively to their levels at the diagnostic time.

This outcome focuses on assessing the levels of cytokines secreted by immune cells, including interferons (IFNs), interleukins (ILs), and tumor necrosis factor (TNF). The objective is to understand cytokine dynamics and their role in the immune response. The assessment will involve cytokine profiling by flow cytometry or ELISA. The levels of IFNs, ILs, and TNF will be measured as a percentage of change over a period of 60 months, relative to their levels at the diagnostic time. This standardized approach of using a common unit of measure will enable a comprehensive and unified evaluation of cytokine variations, providing critical insights into the immune response dynamics throughout the study duration.

This outcome aims to evaluate the presence and distribution of TILs within the tumor microenvironment. The objective is to understand the role of TILs in the immune response against the tumor. The assessment will involve analyzing tissue samples for TIL presence and distribution by immunohistochemistry (IHC) or flow cytometry.

This outcome focuses on investigating the expression of immune checkpoint molecules, specifically programmed cell death protein 1 (PD-1) and cytotoxic T-lymphocyte-associated protein 4 (CTLA-4). The objective is to understand the role of immune checkpoints in regulating the immune response. The assessment will involve evaluating immune checkpoint expression using techniques such as flow cytometry or PCR. The levels of PD-1 and CTLA-4 expression will be measured in the percentage of change over a period of 60 months, relative to their levels at the diagnostic time. Utilizing a standardized common unit of measure ensures a uniform assessment, allowing for a comprehensive understanding of the immune checkpoint dynamics and their impact on the immune response throughout the study's duration.

This outcome aims to assess alterations in angiogenic factors, with a specific focus on Vascular Endothelial Growth Factor (VEGF), in relation to treatment and study outcomes. VEGF is a key regulator of angiogenesis and is associated with tumor vascularization. The serum concentrations of VEGF-A/C will be measured by ELISA, providing valuable insights into the angiogenic processes linked to the immune response and their potential impact on treatment outcomes.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Association of SNPs in Long Intergenic Noncoding RNA 00511 (LINC00511) With Breast Cancer Among the Egyptian Population	NCT06357689	Breast Cancer		20 Years - 70 Years	Ain Shams University
Exploring Cancer-Associated Thromboembolism Prognosis Biomarkers and Polymorphisms	NCT06065592	Cancer Solid Tumor Thromboembolism Cardiovascular ... Immune System D... Inflammatory Di... Colon Cancer Breast Cancer Prostate Cancer Hepatocellular ... Lung Cancer Chemotherapy Immunotherapy	Palbociclib Rivaroxaban SNP	18 Years -	Lebanese University
Exploring Cancer-Associated Thromboembolism Prognosis Biomarkers and Polymorphisms	NCT06065592	Cancer Solid Tumor Thromboembolism Cardiovascular ... Immune System D... Inflammatory Di... Colon Cancer Breast Cancer Prostate Cancer Hepatocellular ... Lung Cancer Chemotherapy Immunotherapy	Palbociclib Rivaroxaban SNP	18 Years -	Lebanese University
Association of SNPs in Long Intergenic Noncoding RNA 00511 (LINC00511) With Breast Cancer Among the Egyptian Population	NCT06357689	Breast Cancer		20 Years - 70 Years	Ain Shams University

Spots Global Cancer Trial Database for lncrna

Every month we try and update this database with for lncrna cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Spots Global Cancer Trial Database for lncrna

Every month we try and update this database with for lncrna cancer trials from around the world to help patients and their families find trials that might be right for them. We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Every month we try and update this database with for lncrna cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.